BMS and Nektar Expand Strategic Collaboration to Advance Bempegaldesleukin plus Opdivo Combination in Multiple Tumor Types

November 13, 2019 News /BioValleyBIOON/ -- Nektar Therapeutics and its partner Bristol-Myers Squibb (BMS) recently announced a new joint development plan to advance the immunotherapy combination of bempegaldesleukin (bempeg, NKTR-214) and Opdivo (generic name: nivolumab) into multiple new registrational trials.

The revision of the strategic cooperation agreement between the two parties includes a new joint development plan, under which Nektar and BMS will expand the clinical development program for the bempeg + Opdivo combination, extending from three ongoing registrational trials (first-line treatment of metastatic melanoma, first-line treatment of cisplatin-ineligible metastatic urothelial carcinoma, and first-line treatment of metastatic renal cell carcinoma [RCC]) to include two additional registrational trials (adjuvant therapyMelanoma, muscle-invasive bladder cancer). In addition, the two parties will initiate a Phase I/II dose-escalation and expansion study to evaluate the combination of bempeg plus Opdivo with axitinib as first-line treatment for RCC, to support future registration trials.

The costs of these studies will be allocated in accordance with the cost-sharing provisions outlined in the original collaboration agreement. As part of the new strategic collaboration agreement, BMS will independently conduct and fund a Phase I/II dose optimization and expansion study evaluating bempeg plus Opdivo as first-line treatment for non-small cell lung cancer (NSCLC).

BMS and Nektar entered into a clinical collaboration in September 2016 to evaluate the Opdivo/bempeg combination therapy for the treatment of various types of cancer. In February 2018, the two parties further reached a global strategic development and commercialization collaboration valued at up to $3.6 billion, jointly developing NKTR-214 with Opdivo and Opdivo + Yervoy across nine indications.TumorCombination applications in more than 20 types of indications, as well as combinations with other anticancer drugs from two companies or third parties. Currently, the bempeg/Opdivo immunotherapy combinationMelanomaand renal cell carcinoma (RCC) has entered Phase III clinical trials.In August 2019, BMS and Nektar Therapeutics announced that the United StatesFDAThe BEMPEG + Opdivo combination therapy has been granted Breakthrough Therapy Designation (BTD) for the treatment of previously untreated unresectable or metastaticMelanomaPatient.

At the 2019 Annual Meeting of the Society for Immunotherapy of Cancer (SITC), both parties announced results from the Phase I/II PIVOT-02 study on the first-line treatment of metastatic (Stage IV) cancer with the bempeg + Opdivo immunotherapy combination.MelanomaLatest Patient Data. Data as of September 25, 2019, show: (1) With a median follow-up of 18.6 months, among efficacy-evaluable patients (n=38), the confirmed objective response rate (ORR) was 53% (20/38), and the complete response rate (CR) was 34% (13/38). Forty-two percent (16/38) of patients achieved a 100% reduction in target lesions. The disease control rate (DCR: complete response + partial response + stable disease) was 74% (28/38). (2) The median time to response was 2.0 months, and the median time to complete response was 7.9 months. (3) The median reduction in target lesions from baseline was 61.5%. (4) At a median follow-up of 18.6 months, the median duration of response (DOR) had not been reached, with 85% (17/20) of responders maintaining their response. (5) Among 35 patients with known baseline PD-L1 status, the ORRs were 39% (5/13) in PD-L1-negative patients and 64% (14/22) in PD-L1-positive patients. (6) At a median follow-up of 18.6 months, the median progression-free survival (PFS) had not been reached (95% CI: 5.3–NE). (7) The combination of BEMPEG + Opdivo was well tolerated, with treatment-related adverse events being predictable and transient.

Bempegaldesleukin (NKTR-214) Stimulates the Proliferation of Anti-Cancer Immune Cells

NKTR-214 is a CD122-biased IL-2 pathway agonist that stimulates the proliferation of these anticancer immune cells in vivo by targeting the CD122-specific receptors present on the surface of natural killer (NK) cells, CD4+ T cells, and CD8+ T cells. CD122, also known as the interleukin-2 receptor beta subunit, is an important signaling receptor known to enhance the proliferation of these effector T cells. In preclinical and clinical studies, treatment with NKTR-214 resulted in rapid expansion and mobilization of these cells toTumorinto the microenvironment.

Opdivo is a PD-1 immune checkpoint inhibitor designed to overcome immunosuppression, while NKTR-214 is an immunostimulatory therapy that has been shown to increase tumor-infiltrating cells, T-cell clonality, and PD-1 expression. Opdivo and NKTR-214 have two distinct, complementary mechanisms of action; combining the two enhances the body’s immune system ability to fight cancer, and this combination has been demonstrated to elevate baselineTumorTransition from PD-L1 negative (<1%) to PD-L1 positive (≥1%).

Increase in the bodyTumorSupplementing the immune system with tumor-infiltrating lymphocytes (TILs) is crucial, as many patients lack sufficient TIL populations and therefore struggle to benefit from currently approved immune checkpoint inhibitors. Combining immune checkpoint inhibitors with T-cell proliferation can produce synergistic effects, thereby offering patients a new therapeutic option. (Bioon.com)

Original Source:Nektar Therapeutics and Bristol-Myers Squibb Amend Strategic Collaboration Agreement for bempegaldesleukin Plus Opdivo (nivolumab)