Replies to post #661966 on NorthWest Biotherapeutics Inc (NWBO)

[StonkMaster]

I don't believe this is DCVax-L.

[ae kusterer]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449174/#:~:text=Dendritic%20cells%20(DCs)%20initiate%20adaptive,in%20rejecting%20tumors%20from%20mice.


"Dendritic cells (DCs) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax®-Direct) were superior to immature DCs in rejecting tumors from mice."


saxxie2
Saturday, January 06, 2024 12:32:09 PM
Post#
661966

Colorectal Cancer trial to start next month!

https://classic.clinicaltrials.gov/ct2/history/NCT05518032?A=1&B=10&C=merged#StudyPageTop



History of Changes for Study: NCT05518032
Pembrolizumab and Autologous Dendritic Cells for the Treatment of Refractory Colorectal Cancer (CRC)
Latest version (submitted January 4, 2024) on ClinicalTrials.gov
A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 August 24, 2022 None (earliest Version on record)
2 September 13, 2022 Study Status
3 October 20, 2022 Study Status
4 December 12, 2022 Study Status
5 February 16, 2023 Study Status
6 May 31, 2023 Study Status
7 July 28, 2023 Study Status
8 September 19, 2023 Study Status
9 November 13, 2023 Study Status
10 January 4, 2024 Study Status
Comparison Format:
Merged
Side-by-Side
Scroll up to access the controls
Changes (Merged) for Study: NCT05518032
August 24, 2022 (v1) -- January 4, 2024 (v10)

Changes in: Study Status
Show only changed modules
Open or close this module Study Identification
Unique Protocol ID: I - 1670021
Brief Title: Pembrolizumab and Autologous Dendritic Cells for the Treatment of Refractory Colorectal Cancer (CRC)
Official Title: A Phase 2 Study of Intravenous Pembrolizumab and Intratumorally Injected Autologous Dendritic Cells (DCs) in Refractory Colorectal Cancer (CRC)
Secondary IDs: NCI-2022-04955 [Registry Identifier: CTRP (Clinical Trial Reporting Program)]
I - 1670021 [Roswell Park Cancer Institute]
Open or close this module Study Status
Record Verification: August 2022 January 2024
Overall Status: Not yet recruiting
Study Start: September 1, 2022 February 15, 2024
Primary Completion: September 1 December 15, 2024 2025 [Anticipated]
Study Completion: September 1 December 15, 2024 2025 [Anticipated]
First Submitted: August 24, 2022
First Submitted that
Met QC Criteria: August 24, 2022
First Posted: August 26, 2022 [Actual]
Last Update Submitted that
Met QC Criteria: August 24, 2022 January 4, 2024
Last Update Posted: August 26, 2022 [Actual] January 5, 2024 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Roswell Park Cancer Institute
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The phase II trial tests whether pembrolizumab and dendritic cell-based treatment works to shrink tumors in patients with colorectal cancer that does not respond to treatment (refractory). Pembrolizumab, also referred to as an immune checkpoint inhibitor drug, works by targeting molecules that act as a check and balance system for immune responses. Immune checkpoint inhibitor drugs are designed to either "unleash" or "enhance" the cancer immune responses that already exist by either (1) blocking inhibitory molecules or by (2) activating stimulatory molecules. Dendritic cell-based treatment works by boosting the immune system (a system in our bodies that protects us against infection) to recognize and destroy the cancer cells. This investigational treatment targets cancer cells and is made from the patient's own blood cells. Giving pembrolizumab and dendritic cell-based treatment may help shrink tumors in patients with colorectal cancer.
Detailed Description: PRIMARY OBJECTIVE:
I. To determine the clinical efficacy of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in refractory metastatic colorectal cancer (CRC).

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in CRC patients.

II. To assess progression-free survival (PFS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).

III. To assess overall survival (OS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).

IV. To assess objective response as determined by Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).

EXPLORATORY OBJECTIVES:

I. To conduct correlative science studies including:

Ia. Comparison of the metastatic tissue specimen with regard to total numbers of infiltrating T cells, their CD4/CD8 ratios, frequencies of Tregs, and their expression of chemokine receptors.

Ib. Evaluate the local expression of T eff-attracting chemokines and T reg-favoring chemokines using immunofluorescence (IF) and reverse transcription-polymerase chain reaction (RT-PCR).

OUTLINE:

Patients receive pembrolizumab intravenously (IV) on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50.

After completion study treatment, patients are followed up at 30 and 90 days, and then every 3 months for 12 months.

Open or close this module Conditions
Conditions: Metastatic Microsatellite Stable Colorectal Carcinoma
Recurrent Colorectal Carcinoma
Stage III Colorectal Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Unresectable Colorectal Carcinoma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 20 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Treatment (pembrolizumab, autologous dendritic cells)
Patients receive pembrolizumab IV on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50.
Procedure: Biopsy
Undergo biopsy
Other Names:
BIOPSY_TYPE
Bx
Biological: Pembrolizumab
Given IV
Other Names:
Keytruda
Lambrolizumab
MK-3475
SCH 900475
Biological: Therapeutic Autologous Dendritic Cells
Given intratumorally
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Objective response rate
[ Time Frame: At 12 weeks ]

Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.
Secondary Outcome Measures:
1. Incidence of toxicities and adverse events
[ Time Frame: Up to 90 days after last dose ]

Assessed as per Common Terminology Criteria for Adverse Events version 5.0 and tabulated by type and grade.
2. Progression-free survival
[ Time Frame: From initiation of study treatment regimen to disease progression or death from any cause, assessed up to 1 year ]

Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 90% confidence intervals.
3. Overall survival
[ Time Frame: From the time of treatment initiation until death from any cause, assessed up to 1 year ]

Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 90% confidence intervals.
4. Objective response rate
[ Time Frame: Up to 1 year ]

Determined by Immune-related RECIST. Will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria: Inclusion Criteria:
Age >= 18 years of age
Recurrent and/or metastatic unresectable microsatellite stable (MSS) colorectal cancer
At least 2 target lesions present per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at least one of which is amenable to biopsy and injection
Prior treatment with, contra-indication to, or refusal of a fluoropyrimidine, irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wt), as well as avastin/bevacizumab
PD-1/PD-L1/PD-L2 treatment naïve patients are eligible
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Platelet >= 75,000/uL
Hemoglobin >= 8 g/dL (without transfusion in the past 14 days)
Absolute neutrophil count (ANC) >= 1500/uL
Estimated creatinine clearance (Cockcroft Gault) >= 30 mL/min/ for participant with creatinine levels > 1.5 x institutional upper limit of normal (ULN)
Total bilirubin: =< 2 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 2 x ULN
Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 3 x institutional ULN (=< 5 x ULN for participants with liver metastases)
Women of childbearing potential must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood: This may be a period of several years. Methods for acceptable birth control include condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used
NOTE: If the risk of conception exists, patients must continue to use highly effective contraception for at least two years following the last study treatment administration
A male participant must agree to use a contraception during the treatment period and for at least 1 year after the last dose of study treatment and refrain from donating sperm during this period
Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Exclusion Criteria:

Patients currently treated with systemic immunosuppressive agents. If a patient is currently on steroids, they must be on a steroid dose less than or equal to an equivalent prednisone dose of 10 mg daily
Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
Has received prior chemotherapy or radiotherapy within 2 weeks of start of study intervention. All chemotherapy or radiation-related toxicities must be resolved to =< grade 1, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection. Note: No HIV testing is required
Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Open or close this module Contacts/Locations
Study Officials: Sarbajit Mukherjee
Principal Investigator
Roswell Park Cancer Institute
Locations: United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Contact:Contact: Sarbajit Mukherjee 716-845-7504 [e-mail]
Contact:Principal Investigator: Sarbajit Mukherjee
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:
Scroll up to access the controlsScroll to the Study top
U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services



DCVax® – Direct
Our DCVax-Direct product offers a potential new treatment option for the wide range of clinical situations in which patients’ tumors are considered “inoperable” because the patient has multiple tumors, or their tumor cannot be completely removed, or the surgery would cause undue damage to the patient and impair their quality of life.

A large number of patients with a variety of cancer types (including lung, colon, pancreatic, liver, ovarian, head and neck, and others) are faced with this situation, because their tumors are already locally advanced or have begun to metastasize by the time symptoms develop and the patients seek treatment. For these patients, the outlook today is bleak and survival remains quite limited.

DCVax-Direct is administered by direct injection into a patient’s tumors. It can be injected into any number of tumors, enabling patients with locally advanced disease or with metastases to be treated. DCVax-Direct can also be injected into tumors in virtually any location in the body: not only tissues at or near the surface of the body but also, with ultra-sound guidance, into interior tissues.

We are currently conducting a 60-patient Phase I/II trial of DCVax-Direct for all types of inoperable solid tumors. The trial is under way at MD Anderson in Houston, TX and MD Anderson in Orlando, FL, with additional sites in varying stages of preparation. The Phase I stage of the trial involves dose escalation, testing 3 different dose levels of DCVax-Direct, and confirmation of the optimal dose. The Phase II stage of the trial will focus on efficacy. The primary measure of efficacy will be regression (i.e., shrinkage or elimination) of the patient’s existing inoperable tumors. Such regression is a rapid endpoint: if it is going to occur, is anticipated to occur within a couple months of treatment.

To learn the eligibility criteria for the DCVax-Direct trial, please visit ClinicalTrials.gov.

Follow us On:
DCVAX® TECHNOLOGY
About DCVax®
Dendritic Cell Immunotherapy
Patient Stories & Physician Comments
PRODUCT CANDIDATES
DCVax® – L
DCVax® – Direct
DCVax® – Prostate
CLINICAL TRIALS
Pipeline
DCVax® – L Phase III
DCVax® – Direct Phase I/II
INVESTORS & MEDIA
Contacts

https://www.clinicaltrials.gov/study/NCT01882946

HomeSearch ResultsStudy Record
Disclaimer

The U.S. government does not review or approve the safety and science of all studies listed on this website.

Read our full disclaimer for details.

UNKNOWN STATUS
Safety and Efficacy Study of DCVax-Direct in Solid Tumors
ClinicalTrials.gov ID NCT01882946
Sponsor Northwest Biotherapeutics
Information provided by Northwest Biotherapeutics (Responsible Party)
Last Update Posted 2015-10-07

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Study DetailsTable ViewNo Results PostedRecord History
On this page
Study Overview
Brief Summary
The study comprises a Phase I component during which the optimal dose of DCVax-Direct for the treatment of solid tissue tumors will be identified, followed by a Phase II component to determine if the injection of DCVax-Direct into selected solid tissue tumors has the ability to reduce tumor growth.
Official Title
A PHASE I/II CLINICAL TRIAL EVALUATING DCVax-Direct, AUTOLOGOUS ACTIVATED DENDRITIC CELLS FOR INTRATUMORAL INJECTION, IN PATIENTS WITH SOLID TUMORS
Conditions
Locally Advanced Tumor
Metastatic Solid Tissue Tumors
Liver Cancer
Colorectal Cancer
Show 2 more conditions
Intervention / Treatment
Biological: DCVax-Direct
Other Study ID Numbers
NWBio 050012
Study Start
2013-06
Primary Completion (Estimated)
2016-12
Study Completion
Enrollment (Estimated)
60
Study Type
Interventional
Phase
Phase 1
Phase 2
Resource links provided by the National Library of Medicine
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.

United States
Florida Locations
Orlando, Florida, United States, 32806
Orlando Health
Texas Locations
Houston, Texas, United States, 77030
MD Anderson Cancer Center
Click to view interactive map
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.
Eligibility Criteria
Description
Inclusion Criteria (summary):

Age between 18 and 75 years (inclusive) at screening.
Karnofsky performance status (KPS) of 70 or higher or Eastern Cooperative Oncology Group (ECOG) 0-1 at screening.
Subjects with a histological or cytopathological confirmed diagnosis of a locally advanced or metastatic solid tumor malignancy for which primary treatment is no longer effective or does not offer curative or life-prolonging potential per clinician judgment, with the understanding that DCVax-Direct is not intended as a treatment of last resort.
Not eligible for complete resection due to either tumor location, physician's assessment or subject's choice.
Must have completed at least one recent treatment regimen in the metastatic or advanced setting in the disease currently under treatment to reduce tumor burden.
Any steroid therapy >2 mg dexamethasone or equivalent dose should be stopped or have been tapered down 2 weeks prior to the leukapheresis.
At least one measurable tumor mass, i.e. a lesion that can accurately be measured by CT/MRI in at least one dimension with longest diameter = 1 cm, that is accessible for injection either with or without imaging (CT/ultrasound) guidance.
Adequate hematological, hepatic, and renal function,
Adequate blood coagulation parameters
Life expectation of >3 months.
Exclusion Criteria (Summary):

Positive HIV-1, HIV-2, or Human T-lymphotropic virus (HTLV-I/II) tests.
History of current or prior (within the last two years) active clinically significant malignancy other than the tumor type for which DCVax-Direct treatment is considered, and except for primary tumor in the case of metastases and adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
Heavily pretreated (HP) subjects are not eligible for this study, unless treatments have occurred more than 1 year in the past.
Presence of brain metastases, unless treated surgically and/or irradiated and clinically stable off steroids or on low dose (< 2 mg per day) steroids for = 14 days, or presence of leptomeningeal disease.
History of immunodeficiency or unresolved autoimmune disease.
Requirement for ongoing immunosuppressants.
Prior active immunotherapy for cancer within the past 2 years.
Ongoing medical need for continuous anti-coagulation or anti-platelet medication.
Known genetic cancer-susceptibility syndromes.
Acute or active uncontrolled infection
Ongoing fever = 101.5 degrees F/38.6 degrees C at screening.
Unstable or severe intercurrent medical conditions such as unstable angina, uncontrolled arrhythmias, Crohn's Disease, ulcerative colitis etc.
Females of child-bearing potential who are pregnant or lactating or who are not using adequate contraception (surgical, hormonal or double barrier, i.e. condom and diaphragm).
Allergy or anaphylaxis to any of the reagents used in this study.
Inability to obtain informed consent because of psychiatric or complicating medical problems.
Inability or unwillingness to return for required visits and follow-up exams.
Show more
Ages Eligible for Study
18 Years to 75 Years (Adult, Older Adult )
Sexes Eligible for Study
All
Accepts Healthy Volunteers
No
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.

Expand all / Collapse all
How is the study designed?
What is the study measuring?
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Northwest Biotherapeutics
Collaborators
No information provided
Investigators
Study Director:Marnix Bosch, MBA, PhD,Northwest Biotherapeutics
Publications
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications

No publications available
* Find Publications about Study Results and related Pubmed Publications in the “Results” section of the study record.

Study Record Dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Registration Dates
First Submitted
2013-06-14
First Submitted that Met QC Criteria
2013-06-20
First Posted (Estimated)
2013-06-21
Study Record Updates
Last Update Submitted that met QC Criteria
2015-10-06
Last Update Posted (Estimated)
2015-10-07
Last Verified
2015-10
More Information
Record History
Expand all / Collapse all
Terms related to this study

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Revision: v2.2.4

[Doc logic]

saxxie2,

Merck trying to compare Direct to other immature DCs. Others will demonstrate minimal benefit by comparison to Direct based on Triozzi et al ; ). Best wishes.

[ae kusterer]

saxxie2 : Could Keytruda be switched to sub Q in the study(starts 2/15/24) to get patent extension?

Re: None

Saturday, January 06, 2024 12:32:09 PM

Post#
661966
of 661987
Colorectal Cancer trial to start next month!

https://classic.clinicaltrials.gov/ct2/history/NCT05518032?A=1&B=10&C=merged#StudyPageTopae kusterer

Re: None

Saturday, January 06, 2024 1:53:33 PM

Post#
661981
of 661986
Jimghad
30 May 2023, 2:11 PM

The future of MRK depends on the extension of Keytruda patent related to their Sub-Q mode of delivery. I totally agree with you.
Bridion and Januvia are soon to lose exclusivity

https://seekingalpha.com/article/4608259-merck-solid-pharma-buy-strong-upside-if-keytruda-patents-extended


https://classic.clinicaltrials.gov/ct2/history/NCT05518032?A=1&B=10&C=merged#StudyPageTop

Official Title: A Phase 2 Study of Intravenous Pembrolizumab and Intratumorally Injected Autologous Dendritic Cells (DCs) in Refractory Colorectal Cancer (CRC)



ae kusterer

Re: saxxie2 post# 661966

Saturday, January 06, 2024 1:24:40 PM

Post#
661976
of 661988
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449174/#:~:text=Dendritic%20cells%20(DCs)%20initiate%20adaptive,in%20rejecting%20tumors%20from%20mice.


"Dendritic cells (DCs) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax®-Direct) were superior to immature DCs in rejecting tumors from mice."


saxxie2
Saturday, January 06, 2024 12:32:09 PM
Post#
661966

Colorectal Cancer trial to start next month!

https://classic.clinicaltrials.gov/ct2/history/NCT05518032?A=1&B=10&C=merged#StudyPageTop



History of Changes for Study: NCT05518032
Pembrolizumab and Autologous Dendritic Cells for the Treatment of Refractory Colorectal Cancer (CRC)
Latest version (submitted January 4, 2024) on ClinicalTrials.gov
A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 August 24, 2022 None (earliest Version on record)
2 September 13, 2022 Study Status
3 October 20, 2022 Study Status
4 December 12, 2022 Study Status
5 February 16, 2023 Study Status
6 May 31, 2023 Study Status
7 July 28, 2023 Study Status
8 September 19, 2023 Study Status
9 November 13, 2023 Study Status
10 January 4, 2024 Study Status
Comparison Format:
Merged
Side-by-Side
Scroll up to access the controls
Changes (Merged) for Study: NCT05518032
August 24, 2022 (v1) -- January 4, 2024 (v10)

Changes in: Study Status
Show only changed modules
Open or close this module Study Identification
Unique Protocol ID: I - 1670021
Brief Title: Pembrolizumab and Autologous Dendritic Cells for the Treatment of Refractory Colorectal Cancer (CRC)
Official Title: A Phase 2 Study of Intravenous Pembrolizumab and Intratumorally Injected Autologous Dendritic Cells (DCs) in Refractory Colorectal Cancer (CRC)
Secondary IDs: NCI-2022-04955 [Registry Identifier: CTRP (Clinical Trial Reporting Program)]
I - 1670021 [Roswell Park Cancer Institute]
Open or close this module Study Status
Record Verification: August 2022 January 2024
Overall Status: Not yet recruiting
Study Start: September 1, 2022 February 15, 2024
Primary Completion: September 1 December 15, 2024 2025 [Anticipated]
Study Completion: September 1 December 15, 2024 2025 [Anticipated]
First Submitted: August 24, 2022
First Submitted that
Met QC Criteria: August 24, 2022
First Posted: August 26, 2022 [Actual]
Last Update Submitted that
Met QC Criteria: August 24, 2022 January 4, 2024
Last Update Posted: August 26, 2022 [Actual] January 5, 2024 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Roswell Park Cancer Institute
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The phase II trial tests whether pembrolizumab and dendritic cell-based treatment works to shrink tumors in patients with colorectal cancer that does not respond to treatment (refractory). Pembrolizumab, also referred to as an immune checkpoint inhibitor drug, works by targeting molecules that act as a check and balance system for immune responses. Immune checkpoint inhibitor drugs are designed to either "unleash" or "enhance" the cancer immune responses that already exist by either (1) blocking inhibitory molecules or by (2) activating stimulatory molecules. Dendritic cell-based treatment works by boosting the immune system (a system in our bodies that protects us against infection) to recognize and destroy the cancer cells. This investigational treatment targets cancer cells and is made from the patient's own blood cells. Giving pembrolizumab and dendritic cell-based treatment may help shrink tumors in patients with colorectal cancer.
Detailed Description: PRIMARY OBJECTIVE:
I. To determine the clinical efficacy of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in refractory metastatic colorectal cancer (CRC).

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in CRC patients.

II. To assess progression-free survival (PFS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).

III. To assess overall survival (OS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).

IV. To assess objective response as determined by Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).

EXPLORATORY OBJECTIVES:

I. To conduct correlative science studies including:

Ia. Comparison of the metastatic tissue specimen with regard to total numbers of infiltrating T cells, their CD4/CD8 ratios, frequencies of Tregs, and their expression of chemokine receptors.

Ib. Evaluate the local expression of T eff-attracting chemokines and T reg-favoring chemokines using immunofluorescence (IF) and reverse transcription-polymerase chain reaction (RT-PCR).

OUTLINE:

Patients receive pembrolizumab intravenously (IV) on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50.

After completion study treatment, patients are followed up at 30 and 90 days, and then every 3 months for 12 months.

Open or close this module Conditions
Conditions: Metastatic Microsatellite Stable Colorectal Carcinoma
Recurrent Colorectal Carcinoma
Stage III Colorectal Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Unresectable Colorectal Carcinoma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 20 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Treatment (pembrolizumab, autologous dendritic cells)
Patients receive pembrolizumab IV on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50.
Procedure: Biopsy
Undergo biopsy
Other Names:
BIOPSY_TYPE
Bx
Biological: Pembrolizumab
Given IV
Other Names:
Keytruda
Lambrolizumab
MK-3475
SCH 900475
Biological: Therapeutic Autologous Dendritic Cells
Given intratumorally
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Objective response rate
[ Time Frame: At 12 weeks ]

Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.
Secondary Outcome Measures:
1. Incidence of toxicities and adverse events
[ Time Frame: Up to 90 days after last dose ]

Assessed as per Common Terminology Criteria for Adverse Events version 5.0 and tabulated by type and grade.
2. Progression-free survival
[ Time Frame: From initiation of study treatment regimen to disease progression or death from any cause, assessed up to 1 year ]

Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 90% confidence intervals.
3. Overall survival
[ Time Frame: From the time of treatment initiation until death from any cause, assessed up to 1 year ]

Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 90% confidence intervals.
4. Objective response rate
[ Time Frame: Up to 1 year ]

Determined by Immune-related RECIST. Will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria: Inclusion Criteria:
Age >= 18 years of age
Recurrent and/or metastatic unresectable microsatellite stable (MSS) colorectal cancer
At least 2 target lesions present per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at least one of which is amenable to biopsy and injection
Prior treatment with, contra-indication to, or refusal of a fluoropyrimidine, irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wt), as well as avastin/bevacizumab
PD-1/PD-L1/PD-L2 treatment naïve patients are eligible
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Platelet >= 75,000/uL
Hemoglobin >= 8 g/dL (without transfusion in the past 14 days)
Absolute neutrophil count (ANC) >= 1500/uL
Estimated creatinine clearance (Cockcroft Gault) >= 30 mL/min/ for participant with creatinine levels > 1.5 x institutional upper limit of normal (ULN)
Total bilirubin: =< 2 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 2 x ULN
Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 3 x institutional ULN (=< 5 x ULN for participants with liver metastases)
Women of childbearing potential must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood: This may be a period of several years. Methods for acceptable birth control include condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used
NOTE: If the risk of conception exists, patients must continue to use highly effective contraception for at least two years following the last study treatment administration
A male participant must agree to use a contraception during the treatment period and for at least 1 year after the last dose of study treatment and refrain from donating sperm during this period
Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Exclusion Criteria:

Patients currently treated with systemic immunosuppressive agents. If a patient is currently on steroids, they must be on a steroid dose less than or equal to an equivalent prednisone dose of 10 mg daily
Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
Has received prior chemotherapy or radiotherapy within 2 weeks of start of study intervention. All chemotherapy or radiation-related toxicities must be resolved to =< grade 1, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection. Note: No HIV testing is required
Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Open or close this module Contacts/Locations
Study Officials: Sarbajit Mukherjee
Principal Investigator
Roswell Park Cancer Institute
Locations: United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Contact:Contact: Sarbajit Mukherjee 716-845-7504 [e-mail]
Contact:Principal Investigator: Sarbajit Mukherjee
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:
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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services



DCVax® – Direct
Our DCVax-Direct product offers a potential new treatment option for the wide range of clinical situations in which patients’ tumors are considered “inoperable” because the patient has multiple tumors, or their tumor cannot be completely removed, or the surgery would cause undue damage to the patient and impair their quality of life.

A large number of patients with a variety of cancer types (including lung, colon, pancreatic, liver, ovarian, head and neck, and others) are faced with this situation, because their tumors are already locally advanced or have begun to metastasize by the time symptoms develop and the patients seek treatment. For these patients, the outlook today is bleak and survival remains quite limited.

DCVax-Direct is administered by direct injection into a patient’s tumors. It can be injected into any number of tumors, enabling patients with locally advanced disease or with metastases to be treated. DCVax-Direct can also be injected into tumors in virtually any location in the body: not only tissues at or near the surface of the body but also, with ultra-sound guidance, into interior tissues.

We are currently conducting a 60-patient Phase I/II trial of DCVax-Direct for all types of inoperable solid tumors. The trial is under way at MD Anderson in Houston, TX and MD Anderson in Orlando, FL, with additional sites in varying stages of preparation. The Phase I stage of the trial involves dose escalation, testing 3 different dose levels of DCVax-Direct, and confirmation of the optimal dose. The Phase II stage of the trial will focus on efficacy. The primary measure of efficacy will be regression (i.e., shrinkage or elimination) of the patient’s existing inoperable tumors. Such regression is a rapid endpoint: if it is going to occur, is anticipated to occur within a couple months of treatment.

To learn the eligibility criteria for the DCVax-Direct trial, please visit ClinicalTrials.gov.

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DCVAX® TECHNOLOGY
About DCVax®
Dendritic Cell Immunotherapy
Patient Stories & Physician Comments
PRODUCT CANDIDATES
DCVax® – L
DCVax® – Direct
DCVax® – Prostate
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Pipeline
DCVax® – L Phase III
DCVax® – Direct Phase I/II
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Contacts

https://www.clinicaltrials.gov/study/NCT01882946

HomeSearch ResultsStudy Record
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The U.S. government does not review or approve the safety and science of all studies listed on this website.

Read our full disclaimer for details.

UNKNOWN STATUS
Safety and Efficacy Study of DCVax-Direct in Solid Tumors
ClinicalTrials.gov ID NCT01882946
Sponsor Northwest Biotherapeutics
Information provided by Northwest Biotherapeutics (Responsible Party)
Last Update Posted 2015-10-07

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Study DetailsTable ViewNo Results PostedRecord History
On this page
Study Overview
Brief Summary
The study comprises a Phase I component during which the optimal dose of DCVax-Direct for the treatment of solid tissue tumors will be identified, followed by a Phase II component to determine if the injection of DCVax-Direct into selected solid tissue tumors has the ability to reduce tumor growth.
Official Title
A PHASE I/II CLINICAL TRIAL EVALUATING DCVax-Direct, AUTOLOGOUS ACTIVATED DENDRITIC CELLS FOR INTRATUMORAL INJECTION, IN PATIENTS WITH SOLID TUMORS
Conditions
Locally Advanced Tumor
Metastatic Solid Tissue Tumors
Liver Cancer
Colorectal Cancer
Show 2 more conditions
Intervention / Treatment
Biological: DCVax-Direct
Other Study ID Numbers
NWBio 050012
Study Start
2013-06
Primary Completion (Estimated)
2016-12
Study Completion
Enrollment (Estimated)
60
Study Type
Interventional
Phase
Phase 1
Phase 2
Resource links provided by the National Library of Medicine
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.

United States
Florida Locations
Orlando, Florida, United States, 32806
Orlando Health
Texas Locations
Houston, Texas, United States, 77030
MD Anderson Cancer Center
Click to view interactive map
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.
Eligibility Criteria
Description
Inclusion Criteria (summary):

Age between 18 and 75 years (inclusive) at screening.
Karnofsky performance status (KPS) of 70 or higher or Eastern Cooperative Oncology Group (ECOG) 0-1 at screening.
Subjects with a histological or cytopathological confirmed diagnosis of a locally advanced or metastatic solid tumor malignancy for which primary treatment is no longer effective or does not offer curative or life-prolonging potential per clinician judgment, with the understanding that DCVax-Direct is not intended as a treatment of last resort.
Not eligible for complete resection due to either tumor location, physician's assessment or subject's choice.
Must have completed at least one recent treatment regimen in the metastatic or advanced setting in the disease currently under treatment to reduce tumor burden.
Any steroid therapy >2 mg dexamethasone or equivalent dose should be stopped or have been tapered down 2 weeks prior to the leukapheresis.
At least one measurable tumor mass, i.e. a lesion that can accurately be measured by CT/MRI in at least one dimension with longest diameter = 1 cm, that is accessible for injection either with or without imaging (CT/ultrasound) guidance.
Adequate hematological, hepatic, and renal function,
Adequate blood coagulation parameters
Life expectation of >3 months.
Exclusion Criteria (Summary):

Positive HIV-1, HIV-2, or Human T-lymphotropic virus (HTLV-I/II) tests.
History of current or prior (within the last two years) active clinically significant malignancy other than the tumor type for which DCVax-Direct treatment is considered, and except for primary tumor in the case of metastases and adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
Heavily pretreated (HP) subjects are not eligible for this study, unless treatments have occurred more than 1 year in the past.
Presence of brain metastases, unless treated surgically and/or irradiated and clinically stable off steroids or on low dose (< 2 mg per day) steroids for = 14 days, or presence of leptomeningeal disease.
History of immunodeficiency or unresolved autoimmune disease.
Requirement for ongoing immunosuppressants.
Prior active immunotherapy for cancer within the past 2 years.
Ongoing medical need for continuous anti-coagulation or anti-platelet medication.
Known genetic cancer-susceptibility syndromes.
Acute or active uncontrolled infection
Ongoing fever = 101.5 degrees F/38.6 degrees C at screening.
Unstable or severe intercurrent medical conditions such as unstable angina, uncontrolled arrhythmias, Crohn's Disease, ulcerative colitis etc.
Females of child-bearing potential who are pregnant or lactating or who are not using adequate contraception (surgical, hormonal or double barrier, i.e. condom and diaphragm).
Allergy or anaphylaxis to any of the reagents used in this study.
Inability to obtain informed consent because of psychiatric or complicating medical problems.
Inability or unwillingness to return for required visits and follow-up exams.
Show more
Ages Eligible for Study
18 Years to 75 Years (Adult, Older Adult )
Sexes Eligible for Study
All
Accepts Healthy Volunteers
No
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.

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How is the study designed?
What is the study measuring?
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Northwest Biotherapeutics
Collaborators
No information provided
Investigators
Study Director:Marnix Bosch, MBA, PhD,Northwest Biotherapeutics
Publications
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications

No publications available
* Find Publications about Study Results and related Pubmed Publications in the “Results” section of the study record.

Study Record Dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Registration Dates
First Submitted
2013-06-14
First Submitted that Met QC Criteria
2013-06-20
First Posted (Estimated)
2013-06-21
Study Record Updates
Last Update Submitted that met QC Criteria
2015-10-06
Last Update Posted (Estimated)
2015-10-07
Last Verified
2015-10
More Information
Record History
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Terms related to this study

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Revision: v2.2.4

[dstock07734]

This has nothing to do with DCVax-L. Note that it is the technology developed by Roswell Park Cancer Institute. If I remember correctly, the technology triggers immune system to attack tumor blood vessels. They used the technology for GBM trial. I don't recall patients survived three years.

Have you wondered why the similar collaboration trial between NWBO and Merck disappeared in radar?

[flipper44]

Intratumoral DC Colorectal vaccine with CI (Keytruda) and 90 day phase II primary endpoint and one year secondary endpoint.