NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

Quit bluffing, it was a phase 1 / 2 safety trial, no safety issues. They found systemic response and many patients surviving far beyond when they were supposed to survive. But it was not calculated to give an optimal treatment, as a safety trial.

The patients were unable to get other treatment and were effectively assigned to go to hospice if they could find no other options. They only injected one tumor even if the patients had many. The result was most patients lived longer than expected and some seem to have continued living indefinitely. They had a variety of horrible cancers. They gave different amounts I believe, and different versions of the vaccine.

“Primary Outcome Measures:
Number of patients with adverse events [ Time Frame: 6 months ]”

There were a variety of other measures including survival, but the primary measure was basically SAFETY.

They published the results favorably. They simply did not have the funds to pursue DCVax Direct without having DCVax-L approved.


From the clinical trial:

https://classic.clinicaltrials.gov/ct2/show/NCT01882946

“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.”

Published results below suggest similar biomarker findings to those in the pending paper with poly-iclc and DCVax-L. I expect future trials may include an immune stimulate like poly-iclc and maybe even Keytruda. This was an extremely promising trial.

Here is their presentation from 2019 at ASCO: https://nwbio.com/wp-content/uploads/ASCO-2019-Presentation-FINAL.pdf

Video: https://nwbio.com/update-on-dc-vax-at-asco-2019/

Publication:

https://pubmed.ncbi.nlm.nih.gov/30018119/

“Abstract

Purpose: Dendritic cells (DC) 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. Experimental Design: This single-arm, open-label phase I clinical trial evaluated the safety and efficacy of aDCs, administered intratumorally, in patients with solid tumors. Three dose levels (2 million, 6 million, and 15 million aDCs per injection) were tested using a standard 3 + 3 dose-escalation trial design. Feasibility, immunogenicity, changes to the tumor microenvironment after direct injection, and survival were evaluated. We also investigated cytokine production of aDCs prior to injection. Results: In total, 39 of the 40 enrolled patients were evaluable. The injections of aDCs were well tolerated with no dose-limiting toxicities. Increased lymphocyte infiltration was observed in 54% of assessed patients. Stable disease (SD; best response) at week 8 was associated with increased overall survival. Increased secretion of interleukin (IL)-8 and IL12p40 by aDCs was significantly associated with survival (P = 0.023 and 0.024, respectively). Increased TNFa levels correlated positively with SD at week 8 (P < 0.01). Conclusions: Intratumoral aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes. Clin Cancer Res; 24(16); 3845-56. ©2018 AACR.”