I've written about NKTR-214 (bempegaldesleukin) since 2013.
There was this ~ regarding the NKTR/Opdivo combo trial, PIVOT, from 2018: ASCO 2018 - PIVOT, PIVOT, PIVOT!!!!! (Sorry, FRIENDS flashback to Ross moving a couch in a stairwell!!!) But, really - NKTR-214 plus nivo
This report ~ covering the incredible muckup regarding some batches of Bempeg being "substandard" because they were "out of specification" resulting in "lower results for patients" in an astonishing interview Nektar CEO Howard Robin gave to FiercePharma in 2019: NKTR- 214 (bempegaldesleukin) with Opdivo - PERHAPS the results from the PIVOT trial for melanoma patients were LOWER than they should have been? Meaning if the company who makes it (Nektar) gets its act together patients may demonstrate an even better response????
And in 2020 there was this report ~ in which Bempeg was used in TIL (on mice): TIL ACT for melanoma patients - past and present...
Now, there's this ~ Game over: Bristol Myers, Nektar end $3.6B immuno-oncology program after 2 more late-stage flops, a report by Nick Paul Taylor, April 15, 2022, from FIERCEBiotech, which reads:
Bristol Myers Squibb and Nektar have read the last rites to their huge, failed cancer collaboration. With two more late-stage trials failing, the partners have ended clinical development of a combination they once saw as the future of immuno-oncology. The chances of Bristol Myers’ $1 billion upfront bet on bempegaldesleukin, a prodrug of PEGylated IL-2, paying off shrank last month. One month ago, Bristol Myers revealed a combination of Nektar’s bempeg and its Opdivo failed to improve on the progression-free survival and objective response rate achieved by the PD-1 checkpoint inhibitor as a single agent in previously untreated melanoma patients. The failure triggered the end of another study and raised serious doubts about the future of the combination.
Bristol Myers and Nektar confirmed those doubts late Thursday, revealing the combination has failed in two other clinical trials. In one study, the partners compared their drug cocktail to the investigator’s choice of two tyrosine kinase inhibitors (TKIs), namely Exelixis’ Cabometyx and Pfizer’s Sutent, in metastatic renal cell carcinoma (RCC) patients. The trial looked at intermediate/poor risk and all-risk populations.
A preplanned interim analysis found the investigational combination failed to improve on the overall survival achieved by the TKIs in either population. Faced with the failure, Bristol Myers and Nektar have decided to unblind the trial and perform no more overall survival analyses.
Bristol Myers and Nektar also reported the failure of the combination in patients with cisplatin-ineligible, locally advanced or metastatic urothelial cancer. The single-arm phase 2 clinical trial failed to achieve the objective response rate needed to support the continuation of the program.
After going 0 for 3, Bristol Myers and Nektar have decided to discontinue all other studies of the drug combination. The list of studies now winding down include a pivotal program in muscle-invasive bladder cancer and a pair of phase 1/2 trials in RCC and pediatric tumors. Shares in Nektar fell 17% to around $5 after hours, wiping out the small gains they made after news of the melanoma failure dropped.
The discontinuation of the clinical development program confirms the failure of one of the big bets of Thomas Lynch's time as Bristol Myers’ chief scientific officer. Bristol Myers paid $1 billion upfront, made a $850 million stock purchase at $102.60 a share—a price it only briefly hit in the immediate afterglow of the deal—and committed up to $1.8 billion in milestones, all for a 35% split of global profits.
Bristol Myers put together the mammoth financial package in the belief IL-2 was one of three validated mechanisms in immuno-oncology, the others being PD-1 and CTLA-4. The IL-2 cytokine is the first cancer immunotherapy, with the FDA approving a recombinant form in the early 1990s, but problems such as its poor drug-like properties and toxicity limited uptake. Bempeg was designed to eliminate those problems.
Now - This report is from a source that looks only at the money making aspect of medicine. The existence of this publication ~ FIERCEBiotech ~ and their often first-to-publish accuracy (Over the years I've often found info regarding trials and drug development on their site long before I found it in medical journals!) speaks to the business of medicine. The sad truth is that if the product isn't going to make money for the company in sufficient margins, then it isn't going to be produced on the 'free market'. At times drugs have been protected when the government has stepped in - but that's a whole other story. I am NOT certain (given the obvious crazy in the melanoma PIVOT trial) that the Opdivo/Bempeg combo, nor the use of Bempeg in melanoma affected mice given TIL, offered any real benefit to melanoma patients. Still, given the small share of the cancer market melanoma patients provide and the pronouncement in this article that Nektar and BMS are closing the doors on this immunotherapy combo, it seems unlikely that the PIVOT trial nor any others using Bempeg for melanoma patients will be completed, much less end up as a treatment option.
Hmmm..... $$$$$!!!! We'll see what happens. - c
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