NKTR-102 Demonstrates Sustained Clinical Benefit in 46% of Patients with Metastatic Breast Cancer in Data Presented at 2011 American Society of Clinical Oncology Annual Meeting
High rate of confirmed response maintained in poor prognosis and heavily pre-treated patients including those with visceral disease
Press Release Source: Nektar Therapeutics On Saturday June 4, 2011, 3:00 pm EDT
CHICAGO and SAN FRANCISCO, June 4, 2011 /PRNewswire/ -- Nektar Therapeutics (Nasdaq:NKTR - News) today announced positive results from a Phase 2 clinical study evaluating single-agent NKTR-102 as a second- and third-line treatment in patients with metastatic breast cancer during the 2011 American Society of Clinical Oncology Meeting (ASCO). NKTR-102, a next-generation topoisomerase I inhibitor, is Nektar's lead oncology drug candidate and is being evaluated in multiple cancer indications. The randomized Simon two-stage study presented at ASCO evaluated two 145 mg/m2 dose schedules of single-agent NKTR-102, every two weeks (q14d) and every three weeks (q21d), in 70 metastatic breast cancer patients who failed a prior taxane therapy. Eighty-nine percent (62/70) of patients in the study received a prior anthracycline/taxane with or without capecitabine.
More than one million women worldwide are diagnosed with breast cancer every year and the disease is the leading cause of cancer-related death among women.(1)
A total of 66 of the 70 patients treated with single-agent NKTR-102 in the Phase 2 study were assessable for the primary endpoint of objective tumor response rate (ORR), including confirmed complete responses (CRs) and partial responses (PRs) per RECIST 1.0. As of May 9, 2011, for the q14d day schedule, the confirmed and unconfirmed ORR was 35 percent (11/31) and the confirmed ORR was 32 percent (10/31), including two confirmed CRs. Clinical benefit rate for the 31 evaluable patients in the q14d schedule was 42% (13/31) (defined as confirmed CR+ PR+ Stable Disease (SD) >6 mos). For the q21d schedule, the confirmed and unconfirmed ORR was 31 percent (11/35) and the confirmed ORR was 26 percent (9/35). Clinical benefit rate for the 35 evaluable patients in the q21d schedule was 49% (17/35). Clinical benefit rate for the overall study population was 46%. An additional four patients in the study had near CRs, with 100% disappearance of all target lesions.
"NKTR-102 is emerging as a promising anti-cancer investigational treatment with the potential to become the first topoisomerase I-inhibitor to be used in the fight against breast cancer," said Prof. Ahmad Awada, Head of the Medical Oncology Clinic at the Institut Jules Bordet in Brussels, Belgium. "The drug's high confirmed objective response rate and clinical benefit is very interesting, particularly when one observes that this response rate was maintained in patients pre-treated with anthracyclines, taxanes with or without capecitabine, and also maintained in poor prognosis subsets within the study, such as triple-negative breast cancer and patients with visceral disease."
The confirmed ORR in patients previously treated with anthracycline/taxane/capecitabine was 31% (5/16); confirmed ORR in patients with metastatic triple-negative breast cancer was 39% (7/18); and confirmed ORR in patients with visceral disease was 30% (17/57).
"The every three week dose schedule appears well-tolerated overall and demonstrates encouraging PFS and OS of 5.3 months and 13.1 months, respectively," continued Dr. Awada. "We are in need of effective new therapeutic options whose mechanism of action is different from those already available for women with metastatic breast cancer and we look forward to NKTR-102 entering Phase 3 development."
Patients treated in the single-agent NKTR-102 study had a median of two lines of prior cytotoxic treatments for metastatic disease. Seventy-four percent (52/70) of the patients received neoadjuvant and/or adjuvant therapy and 86% (60/70) had visceral disease.
"The clinical benefit we've observed in multiple tumor settings with NKTR-102, where a highly active topoisomerase 1 inhibitor could be extremely useful, makes us very excited about the future of this new anticancer drug candidate," said Lorianne Masuoka, M.D., Senior Vice President and Chief Medical Officer.
Side effects were generally manageable with dose-limiting toxicity consisting primarily of Grade 3 diarrhea (20-23%) typically occurring after three months of therapy for both schedules. Neuropathy and alopecia were minimal with only one patient experiencing G2 alopecia in the study. Both neuropathy and alopecia are significant adverse events commonly associated with standard breast cancer therapies [Safety Tables, Figures D and E].
NKTR-102 Phase 2 Data Presentation in Metastatic Breast Cancer
Awada et. al., Antitumor activity in a randomized phase II study comparing two schedules of NKTR-102 in patients (Pts) with pretreated metastatic breast cancer (MBC).
Abstract #1034, Poster Board #24
Poster Discussion Session: Breast Cancer - Triple-negative/Cytotoxics/Local Therapy
Session Date and Time: Saturday, June 4, 2011, 2:00 PM – 6:00 PM, Central Time
Location: E450b
Figure A: Efficacy Table: Objective Tumor Response Rate by RECIST (Investigator Assessment)
Response by RECIST v 1.0
NKTR-102
145 mg/m2
q14d
NKTR-102
145 mg/m2
q21d
TOTAL
N
31*
35
66
ORR (confirmed + unconfirmed)
11 (35%)
11 (31%)
22 (33%)
ORR (confirmed)
10 (32%)
9 (26%)
19 (29%)
CR (confirmed)
2 (7%)
0
2 (3%)
PR (confirmed)
8 (26%)
9 (26%)
17 (26%)
SD
12 (39%)
16 (46%)
28 (42%)
PD
9 (29%)
10 (29%)
19 (29%)
Median duration of response
8.3 months
4.4 months
5.8 months
Clinical benefit
(CR+PR+SD>6 months)
13 (42%)
17 (49%)
30 (46%)
Median progression-free survival**
3.5 months
5.3 months
4.6 months
Median overall survival**
8.8 months
13.1 months
10.3 months
*4 patients in the Q14 day arm with no post-baseline scans, but no evidence of progression were excluded from analysis in the evaluable population.
**based on a Kaplan-Meier analysis for the intent-to-treat population.
Figure B: Efficacy Table: Response rate by prior therapy
Prior Therapy Subgroup
Response by RECIST v 1.0
Evaluable Patients
NKTR-102
145 mg/m2
q14d
N=31
NKTR-102
145 mg/m2
q21d
N=35
TOTAL
N=66
Prior A/T only
ORR (confirmed)
7/22 (32%)
5/21 (24%)
12/43 (28%)
Prior A/T in MBC
ORR (confirmed)
3/7 (43%)
2/9 (22%)
5/16 (31%)
Prior A/T/C
ORR (confirmed)
2/6 (33%)
3/10 (30%)
5/16 (31%)
Figure C: Efficacy Table: Response rate by tumor characteristics
Disease Subgroup
Response by RECIST v 1.0
Evaluable Patients
NKTR-102
145 mg/m2
q14d
N=31
NKTR-102
145 mg/m2
q21d
N=35
TOTAL
N=66
ER+ and/or PR+
ORR (confirmed)
8/21 (38%)
4/21 (19%)
12/42 (29%)
Triple-negative breast cancer
ORR (confirmed)
2/8 (25%)
5/10 (50%)
7/18 (39%)
Visceral Disease
ORR (confirmed)
8/25 (32%)
9/32 (28%)
17/57 (30%)
Figure D: Safety Table: Safety-Summary of Drug Related AEs
Most Common Drug-related Grade 3 and 4 Adverse Events > 5% or event of interest
N (%)
NKTR-102
145 mg/m2
q14d
N=35
NKTR-102
145 mg/m2
q21d
N=35
Grade 3
Grade 4
Grade 3
Grade 4
Diarrhea
6 (17%)
1 (3%)
8 (23%)
0
Neutropenia
2 (6%)
2 (6%)
3 (9%)
1 (3%)
Dehydration
3 (9%)
0
4 (11%)
0
Fatigue
4 (11%)
0
3 (9%)
0
Vomiting
3 (9%)
0
0
0
Anaemia
1 (3%)
0
0
1 (3%)
Asthenia
2 (6%)
0
0
0
Lethargy
2 (6%)
0
0
0
Lymphopenia
1 (3%)
1 (3%)
0
0
Neutropenic sepsis
0
0
1 (3%)
0
Febrile neutropenia
0
0
1 (3%)
0
Note: There were two possible treatment-related deaths: sepsis (q21d) and acute renal failure following diarrhea (q14d).
Figure E: Safety Table: Other Safety-Neuropathy and Alopecia
No grade 3 or 4 neuropathy was reported.
NKTR-102
145 mg/m2
q14d
N=35
NKTR-102
145 mg/m2
q21d
N=35
Grade 1
Grade 2
Grade 1
Grade 2
Alopecia
6 (20%)
0
3 (9%)
1 (3%)
About Metastatic Breast Cancer
More than one million women worldwide are diagnosed with breast cancer globally every year(1). The chance of developing invasive breast cancer at some time in a woman's life is a little less than one in eight (12%). There are approximately 200,000 new cases of breast cancer in the United States and 430,000 in Europe each year.(2) Metastatic breast cancer refers to cancer that has spread from the breast to distant sites in the body.
Anthracyclines and taxanes (AT) are the most active and widely used chemotherapeutic agents for breast cancer, but the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Drugs used to treat patients who progress following AT treatment can have response rates as high as 20-30%; however, resistance develops rapidly and new agents with different mechanisms of action, such as topoisomerase I inhibitors, are needed to allow novel ways to overcome the problem of drug resistance. (3) There are currently no FDA-approved topoisomerase I inhibitors to treat breast cancer.
About NKTR-102
Nektar is developing NKTR-102, a next-generation topoisomerase I inhibitor with reduced peak concentrations and a continuous concentration profile. NKTR-102 was invented by Nektar using its advanced polymer conjugate technology platform, and is the first oncology product candidate to leverage Nektar's releasable polymer technology platform.
In addition to the fully-enrolled Phase 2 studies in platinum-refractory/resistant ovarian cancer and metastatic breast cancer, NKTR-102 is also being tested in a separate Phase 2 clinical trial in patients with second-line colorectal cancer and a Phase 1 clinical trial evaluating NKTR-102 in combination with 5-FU therapy. An expansion arm of the Phase 2 study of single-agent NKTR-102 in platinum-refractory/resistant ovarian cancer in women who failed prior Doxil therapy is also currently enrolling. A Phase 3 study of single-agent NKTR-102 is planned in metastatic breast cancer.
