NKTR-102 Demonstrates Significant Efficacy as Single-Agent in Second- or Third-Line Treatment in Metastatic Breast Cancer Patients

Phase 2 Data Presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium

SAN ANTONIO, and SAN FRANCISCO, Dec. 12, 2010 /PRNewswire-FirstCall/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced positive results from a Phase 2 clinical study evaluating single-agent NKTR-102 in patients with metastatic breast cancer during the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS).  NKTR-102, a novel investigational topoisomerase I inhibitor-polymer conjugate, is Nektar's lead oncology candidate and is being evaluated in multiple cancer indications.  The randomized Simon two-stage study presented at SABCS 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-seven percent (61/70) 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 anywhere from 30% to 80% develop metastatic disease.(1)  

A total of 66 of the 70 patients treated in the Phase 2 study were assessable for the primary endpoint of objective tumor response rate (ORR),  including confirmed complete and partial responses per RECIST.  As of October 26, 2010, confirmed ORR for all evaluable patients was 32% (10/31) for the q14d schedule and 26% (9/35) for the q21d schedule, including two confirmed complete responses (CRs) on the q14d schedule.  An additional four patients had near CRs, with 100% disappearance of all target lesions.  The combined ORR for all evaluable patients was 29% (19/66).  Clinical benefit rate for the 66 evaluable patients was 41% (defined as CR+PR+SD greater than or equal to 6 mos).

"These are important new results for NKTR-102 in patients with metastatic breast cancer," said Prof. Ahmad Awada, Head of the Medical Oncology Clinic at the Institut Jules Bordet in Brussels, Belgium.  "The high confirmed objective response rate continues to show that NKTR-102 is one of the most active single agents in this disease.  This is particularly evident given the number of patients with dramatic reduction in lung and liver metastases."

The confirmed ORR was maintained in poor prognosis and heavily pre-treated subsets within the study, including patients previously treated with anthracycline/taxane/capecitabine: 33% (5/15); patients with metastatic triple-negative breast cancer: 39% (7/18); and patients with visceral disease: 29% (17/58).  As of October 26, 2010, preliminary median progression-free survival (PFS) for all patients was 20 weeks. [Efficacy Tables, Figures A - C]

"We are in critical need of effective new therapeutic options whose mechanism of action is different from those already available for women with metastatic breast cancer," continued Dr. Awada.  "This is especially true for those patients whose disease has progressed despite treatment with anthracyclines and taxanes.  NKTR-102 is emerging as an important investigational treatment in metastatic breast cancer and has the potential to be the first topoisomerase 1 inhibitor in this disease.  NKTR-102 should enter Phase 3 clinical studies as quickly as possible."

Patients treated in the single-agent NKTR-102 study had a median of two lines of prior cytotoxic treatments for metastatic disease.  Seventy-three percent (51/70) of the patients received neoadjuvant and/or adjuvant therapy and 87% (61/70) had visceral disease.  

"NKTR-102 is quickly emerging as a very important potential new drug in the fight against cancer," said Lorianne Masuoka, M.D., Senior Vice President and Chief Medical Officer.  "The drug has consistently high response rates as a single-agent in multiple Phase 1 and 2 clinical studies to-date, including our study in platinum-resistant ovarian cancer and now in metastatic breast cancer.  This clinical benefit we've observed in tumor settings, where a highly active topoisomerase 1 inhibitor could be extremely useful, makes us very excited about the future of NKTR-102."

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.  Only one patient of 70 patients treated with NKTR-102 experienced Grade 2 alopecia and no patient experienced grade 3 or 4 neuropathy.  Both neuropathy and alopecia are significant adverse events commonly associated with standard breast cancer therapies [Safety Tables, Figures D and E].

SABCS Presentation

The presentation (P6-11-01) made today at the SABCS 2010 meeting can be found on Nektar's website at http://www.nektar.com/product_pipeline/oncology_nktr-102.html:

  • Awada et. al., "Significant Efficacy in a Phase 2 Study of NKTR-102, a Novel Polymer Conjugate of Irinotecan, in Patients with Pre-Treated Metastatic Breast Cancer (MBC)"

Nektar to Host Investor and Analyst Call/Webcast During SABCS

The call will include a webcast with slide presentation of the data and a summary review by Howard W. Robin, Nektar President and CEO.  The call will feature a review of the data by Dr. Ahmad Awada, Head of the Medical Oncology Clinic at the Institut Jules Bordet in Brussels, Belgium.  The webcast can be accessed live from the home page of Nektar's website at www.nektar.com.

Date and Time:  Sunday, December 12, 2010, 9:00 a.m. – 10:00 a.m. Central Time


 
 

 

 
 

 To access the audio conference call, follow these instructions:


 
 

 

 
 

 Dial: 866-713-8310 (U.S.); (617) 597-5308 (international)


 
 

 Passcode: 36236932 (Nektar is the host)


 
 
   


 

To access the live webcast, please log on to the webcast at least fifteen minutes prior to the scheduled start time.  A replay of this investor event will be available on the Nektar website approximately three hours after the presentation and will be archived for four weeks.

Figure A: Efficacy Table: Objective Tumor Response Rate by RECIST (Investigator Assessment)


 
 



Response by RECIST v 1.0

NKTR-102

145 mg/m²

q14d

ITT/Evaluable

NKTR-102

145 mg/m²

q21d ITT/Evaluable



TOTAL

ITT/Evaluable

 

N

35/31*

35

70/66

 

ORR (confirmed + unconfirmed

11 (31%)/11 (35%)

11 (31%)

22 (31%)/22 (33%)

 

ORR (confirmed)

10 (29%)/10 (32%)

9 (26%)

19 (27%)/19 (29%)

 

 

 

 

 
 

CR (confirmed)

2 (6%)/2 (7%)

0

2 (3%)/2 (3%)

 

PR (confirmed)

8 (23%)/8 (26%)

9 (26%)

17 (24%)/17 (26%)

 

SD

17 (48%)/13 (42%)

17 (48%)

34 (49%)/30 (45%)

 

PD

8 (23%)/8 (26%)

9 (26%)

17 (24%)/17 (26%)

 

 

 

 

 
 

Clinical benefit

(CR+PR+SD greater than or equal to 6 months)

12 (34%)/12 (39%)

15 (43%)

27 (38%)/27 (41%)

 

*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.


 
 
       


 

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

 

Prior A/T only

ORR (confirmed)

7/22 (32%)


 

5/21 (24%)


 

12/43 (28%)


 
 

Prior A/T in MBC

ORR (confirmed)

2/6 (33%)

2/8 (25%)

4/14 (29%)

 

Prior A/T/C

ORR (confirmed)

2/6 (33%)

3/9 (33%)


 

5/15 (33%)


 
 

 
 
       


 

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

 

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%)

9/33 (27%)


 

17/58 (29%)


 
 

 
 
       


 

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%)

 

Fatigue

4 (11%)

0

3 (9%)

0

 

Dehydration

2 (6%)

0

3 (9%)

0

 

Asthenia

2 (6%)

0

0

0

 

Lymphopenia

2 (6%)

0

0

0

 

Vomiting

2 (6%)

0

0

0

 

Neutropenic sepsis

0

0

1 (3%)

0

 

Febrile neutropenia

0

0

1 (3%)

0

 

Posted: December 2010

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