Full Press Release Details
Nektar and Bristol Myers Squibb Announce Update
on Clinical Development Program for Bempegaldesleukin (BEMPEG) in Combination with Opdivo (nivolumab)
(PRINCETON, N.J., & SAN FRANCISCO, April 14,
2022) -- Nektar Therapeutics (NASDAQ: NKTR) and Bristol Myers Squibb (NYSE: BMY) today announced that based on results from pre-planned
analyses of two late-stage clinical studies of bempegaldesleukin (BEMPEG) in combination with Opdivo (nivolumab) in renal cell
carcinoma (RCC) and bladder cancer, the companies have jointly decided to end the global clinical development program for bempegaldesleukin
in combination with Opdivo. These studies and all other ongoing studies in the program will be discontinued.
In the Phase 3 PIVOT-09 study in patients
with previously untreated advanced or metastatic RCC, Nektar and Bristol Myers Squibb were informed by an independent Data
Monitoring Committee (DMC) that a final analysis of objective response rate (ORR) as assessed by Blinded Independent Central Review
(BICR) showed that bempegaldesleukin in combination with Opdivo did not meet the prespecified boundary for statistical
significance in comparison to the tyrosine kinase inhibitor (TKI) control arm in the International Metastatic Renal Cell Carcinoma
Database Consortium (IMDC) intermediate/poor-risk or all-risk populations. An interim analysis of overall survival (OS) also did not
meet the prespecified boundary for statistical significance in either of these populations. Given there was no clinical benefit in
the doublet therapy arm compared to the TKI arm, the companies have decided to unblind the trial and to perform no additional
analyses for the OS endpoint.
In the separate Phase 2 PIVOT-10 study of the bempegaldesleukin/Opdivo
doublet in patients with cisplatin-ineligible, locally advanced or metastatic urothelial cancer, a final ORR analysis assessed by BICR
showed that bempegaldesleukin in combination with Opdivo did not reach an efficacy threshold to support continuing the program
in urothelial carcinoma.
The companies will review the data for both studies
and plan to share the results with the scientific community.
studies of bempegaldesleukin in combination with Opdivo, including a pivotal study
in muscle-invasive bladder cancer (CA045-009), a Phase 1/2 study of the doublet in combination with TKI therapy in 1L RCC (CA045-011)
and a Phase 1/2 study in recurrent and/or refractory pediatric tumors (CA045-020), will be discontinued, allowing patients and their physicians
to consider standard of care treatment options for their specific conditions.
"As a leader in developing innovative therapies
for patients with cancer, we are committed to continuing to explore novel combinations and pathways and advancing research that may help
cancer patients achieve better outcomes," said Jonathan Cheng, senior vice president and head of oncology development, Bristol Myers
Squibb. "We are immensely grateful to the patients and investigators who participated in these studies."
The companies previously announced in March that
two pivotal studies in melanoma would be discontinued based on results in the Phase 3 PIVOT IO-001 study in metastatic melanoma. Over
the coming months, the companies will work jointly to discontinue the clinical program for bempegaldesleukin in
combination with Opdivo.
"We thank BMS for their collaboration on
the studies of bempegaldesleukin. Nektar remains dedicated to the development of therapeutics to treat cancer and auto-immune disease,"
said Jonathan Zalevsky, chief research and development officer of Nektar Therapeutics.
PIVOT-09 is a global, randomized Phase 3 study
evaluating bempegaldesleukin combined with Opdivo versus investigator's choice of a tyrosine kinase inhibitor (TKI) therapy (either
sunitinib or cabozantinib) in patients with previously untreated advanced renal cell carcinoma in the IMDC all-risk and the IMDC intermediate-
or poor-risk categories. A total of 623 patients were randomized 1:1 to receive a combination of bempegaldesleukin 0.006 mg/kg and Opdivo
360 mg every three weeks in an outpatient setting by intravenous infusion or a specified dose of TKI therapy. Patients were treated until
disease recurrence, unacceptable toxicity or withdrawal of consent for up to 24 months. The study is sponsored and conducted by Nektar
PIVOT-10 is a global Phase 2 single-arm study
evaluating bempegaldesleukin combined with Opdivo in patients deemed ineligible for cisplatin therapy including those whose
baseline tumor cells express low levels of PD-L1. A total of 192 patients were enrolled and patients were treated until disease
recurrence, unacceptable toxicity or withdrawal of consent for up to 24 months. The study is sponsored and conducted by Nektar
About Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the most common type
of kidney cancer in adults, accounting for more than 431,000 new cases and 179,000 deaths worldwide each year. RCC is approximately twice
as common in men as in women, with the highest rates of the disease in North America and Europe. The five-year survival rate for those
diagnosed with metastatic, or advanced, kidney cancer is 13.9%.
About Urothelial Carcinoma
Bladder cancer is the 10th most common cancer in
the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line
the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can
occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed
at an early stage, but rates of recurrence are high. Approximately 50% of patients who undergo surgery for muscle-invasive disease will
experience disease recurrence. Additionally, approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease.
For patients with metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated
with systemic therapy. The poor durability of responses in the first-line setting presents a major challenge in the treatment of metastatic
disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.
Bristol Myers Squibb: Creating a Better Future for People with
Bristol Myers Squibb is inspired by a single vision
- transforming patients' lives through science. The goal of the company's cancer research is to deliver medicines that
offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that
have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and
through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge
capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many
parts of a patient's life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis
to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better
Opdivo is a programmed death-1 (PD-1)
immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune
response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment
option across multiple cancers.
Opdivo's leading global development
program is based on Bristol Myers Squibb's scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical
trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program
has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential
role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum
of PD-L1 expression.
In July 2014, Opdivo was the first
PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in
more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company's Opdivo
and Yervoy combination regimen was the first Immuno-Oncology to receive regulatory approval for the treatment of metastatic melanoma
and is currently approved in more than 50 countries, including the United States and the European Union.
OPDIVO (nivolumab), as a single agent, is indicated
for the treatment of adult patients with unresectable or metastatic melanoma.
OPDIVO (nivolumab), in combination with YERVOY
(ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic melanoma.
OPDIVO (nivolumab) is indicated for the adjuvant treatment
of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
OPDIVO (nivolumab), in combination with platinum-doublet
chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors 4 cm or node positive) non-small cell
lung cancer (NSCLC).
OPDIVO (nivolumab), in combination with YERVOY
(ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors
express PD-L1 ( 1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO (nivolumab), in combination with YERVOY
(ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic