ASCO: Mixed reaction to BMS, Nektar’s high-stakes ‘confusing’ I-O trial

Nektar Therapeutics’ much-anticipated data from a study pairing its immuno-oncology prospect NKTR-214 with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo seem to have resulted in a lot of head-scratching.

Top-line data from the phase 1/2 PIVOT trial, released in abstract form last month, sparked a fall in Nektar’s share price after it pointed to a reduction in overall response rate (ORR) for three cancers compared to an earlier readout last year. And it seems the fresh data reported at the ASCO meeting over the weekend didn’t lay those concerns to rest.

PIVOT looked at the combination of CD122-biased agonist NKTR-214—thought to work via the interleukin-2 pathway—and BMS’ PD-1 inhibitor in patients with advanced melanoma, renal cell carcinoma and urothelial cancers. Stage 1 of the trial looked for an initial threshold for response which, if met, would lead to the enrolment of additional patients in each tumor category (stage 2). The outcome of that determines whether a phase 3 trial will be started.

According to the new ASCO data set, for melanoma, the ORR is now 50% (14 of 28 patients in stage 2)—down from 85% last November when 11 of 13 patients responded. Similarly, for renal cell carcinoma, the ORR went from 64% (seven of 11 patients) to 46% (12 of 26) in stage 2. The urothelial cancer ORR was 60% (six of 10 patients) earlier—which met the threshold for additional enrolment—and so far the data on the stage 2 cohort isn’t ready.

While the ASCO data seems to suggest that the ORR rates are on the slide, the company insists that patients in the new data set haven’t been on the combination for long enough to register a response. If that’s the case, the next readout is going to be critical—possibly either at ESMO in October or the SITC immunotherapy conference in November—and, in the meantime, some investors have expressed concern that Nektar and BMS are pitching into an expensive phase 3 program with a fairly limited set of clinical data.

There was some provocative new data on show at ASCO, including results suggesting that NKTR-214 can stimulate PD-L1-negative tumors to start expressing the protein—which, in theory, should make them more likely to respond to PD-1-targeting drugs like Opdivo, which doesn’t have much activity in PD-L1-negative tumors on its own.

The two partners now say they are planning to start a pivotal trial in melanoma in the third quarter and are in the planning stages for phase 3 renal cell carcinoma and urothelial cancer trials. Meanwhile, enrollment is still ongoing in PIVOT study which intends to recruit over 400 patients with melanoma, renal cell, urothelial, non-small cell lung and triple-negative breast cancers before it completes.

The data prompted plenty of debate at ASCO as observers sifted through the numbers, although given the small sample sizes, it’s arguably not surprising that the results are open to question.

BMS first bought into NKTR-214 in 2016, shortly after Opdivo failed a phase 3 trial in first-line non-small cell lung cancer (NSCLC). Earlier this year, the company upped the ante on the deal, offering $1 billion upfront out of a total potential value of $3.6 billion.

Nektar's pre-market shares dropped nearly 30% Monday morning on its data, coming despite its plea for patience, while partner Bristol was off just under 1%, although it has a other ASCO data updates.