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Nektar (NKTR) Ends Bempeg Plus Opdivo Program on Study Failures

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Nektar Therapeutics (NKTR - Free Report) announced that its lead pipeline candidate, bempegaldesleukin (bempeg), is unlikely to meet primary endpoints in two separate clinical studies evaluating it in renal cell carcinoma (RCC) and bladder cancer. The studies were evaluating bempeg in combination with Bristol-Myers’ (BMY - Free Report) anti-PD-1 drug, Opdivo.

Nektar and Bristol-Myers were developing the combination regimen of bempeg and Opdivo targeting multiple oncology indications under a collaboration agreement signed in 2018. The companies have decided to discontinue these two studies as well as all other ongoing studies in the program following the dismal study data readout. Please note that another registrational study evaluating the combo regimen as a first-line treatment for melanoma patients failed last month. The companies discontinued the development of the combination regimen in melanoma patients, including another clinical study in adjuvant melanoma.

The pre-planned analysis of the phase III PIVOT-09 study evaluating bempeg plus Opdivo in patients with previously untreated advanced renal cell carcinoma demonstrated that the combination regimen failed to meet the pre-specified boundary for statistical significance for objective response rate (ORR) compared to a tyrosine kinase inhibitor (TKI) therapy in the comparator-arm of the study. The combination regimen also failed to meet the pre-specified boundary for statistical significance for overall survival, per an interim analysis.

The final analysis of the phase II PIVOT-10 study showed that the bempeg and Opdivo doublet therapy did not reach an efficacy threshold for ORR to support continuing evaluation of the regimen in patients with locally advanced or metastatic urothelial cancer or bladder cancer.

Nektar and Bristol-Myers were also evaluating the bempeg doublet regimen in patients with muscle-invasive bladder cancer in a pivotal study. Two ongoing phase I/II studies were evaluating the regimen in recurrent and/or refractory pediatric tumors. The failure of bempeg plus Opdivo in pivotal studies in three oncology indications has led the companies to discontinue the development of the combo regimen. The companies will work jointly to discontinue the clinical program over the coming months.

The failure of the bempeg plus Opdivo program is a major setback for Nektar as bempeg is its leading pipeline candidate. Moreover, the candidate's development in combination with Opdivo was its only pivotal stage program. Other development programs for bempeg and other pipeline candidates are in early- to mid-stage studies. The failure is likely to delay Nektar’s prospects of becoming a commercialized biotech by several years. Nektar shares have declined 54.4% so far this year, majorly due to the failure of the bempeg plus Opdivo program, compared with the industry’s decrease of 15.6%.

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The failure of this program has also hurt Bristol-Myers as the company had paid Nektar $1 billion upfront as part of their collaboration agreement and also invested $850 million in Nektar’s common shares at a price of $102.60 per share, which declined almost 94% as of last week.

Apart from Opdivo, Nektar’s bempeg development programs include the combination regimen with Merck’s (MRK - Free Report) Keytruda. The phase I/II study — PROPEL — is evaluating bempeg in combination with Merck’s Keytruda for treating metastatic non-small cell lung cancer. Initial data from the study presented in November last year showed that bempeg plus Merck’s Keytruda demonstrated early evidence of clinical benefit. A phase II/III study is evaluating bempeg plus Merck’s Keytruda as a first-line treatment for metastatic or unresectable recurrent squamous cell carcinoma of the head and neck in patients whose tumors express PD-L1.

Apart from bempeg, Nektar is developing NKTR-255 for treating several oncology indications and NKTR-358 targeting auto-immune indications.

Nektar’s partner, Eli Lilly (LLY - Free Report) is evaluating NKTR-358 in two mid-stage studies involving patients with lupus or ulcerative colitis. Lilly plans to initiate two more mid-stage studies to evaluate the candidate as a potential treatment for atopic dermatitis and another undisclosed auto-immune indication. Lilly initiated the atopic dermatitis study based on data from a proof-of-concept study, which demonstrated sustained disease control for at least six months following treatment with NKTR-358.

Zacks Rank

Nektar currently has a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.


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