- While drugmakers continue to hunt for second-generation cancer immunotherapies, the search has yet to turn up the kind of unambiguous clinical results that some had hoped to see, cooling investor optimism in the process.
- At the Society for Immunotherapy of Cancer's annual meeting over the weekend, dozens of biotechs and pharmas presented fresh data from early studies of compounds they hope can improve on the success of drugs like Merck & Co.'s Keytruda and Bristol-Myers Squibb's Opdivo.
- The generally mixed results unveiled demonstrate the challenge drugmakers face hitting that goal. And while most research remains in initial stages, investors appear to be losing patience. Shares in Tesaro and Aduro Biotech, for example, sold off heading into the meeting.
Many of the drugmakers currently pushing into immuno-oncology aim to develop partner drugs that will work with existing immunotherapies.
The key question facing these companies is whether the evidence they uncover shows signs of improving on the known clinical profiles of drugs like Keytruda (pembrolizumab) and Opdivo (nivolumab). In the wake of a high-profile clinical failure from Incyte's immunotherapy epacadostat earlier this year, industry observers have questioned whether the field has moved too quickly into development of combinations.
"Certainly we're not dissuaded by the epacadostat story," said Eric Rubin, head of oncology early development at Merck Research Laboratories, in an interview with BioPharma Dive. "I think it is just a matter of — in that particular case — decisions on how much information or evidence you need before you embark on a Phase 3."
Merck had partnered with Incyte on the Phase 3 study of epacadostat and Keytruda in advanced melanoma.
At SITC, Merck presented Phase 1 data on two compounds it's developed, MK-4280 and MK-7684, that are designed to block immune suppression. Both studies tested the experimental drugs together with Keytruda in solid tumors.
Efficacy results, however, came in lower than expectations. MK-4280 plus Keytruda resulted in a 27% overall response rate (4 of 15 patients), while MK-7684 and Keytruda led to a 19% overall response rate (8 of 43 patients).
"While the data for both of Merck’s early stage assets that they presented look sufficient to move forward with phase 2 studies, the data were far from differentiating and the investors we spoke with at the conference do not have confidence that either asset could become a meaningful contributor down the road," wrote Credit Suisse analyst Vamil Divan in a Nov. 12 note.
Unsurprisingly, Merck's Rubin had a more optimistic take.
"There was evidence of monotherapy activity in both cases and then, in combination, we also cases where you might not have expected a lot of activity for Keytruda alone," Rubin explained, describing a patient with colon cancer who was microsatellite stable treated with MK-4280 and Keytruda.
Nektar emerged from SITC with perhaps the strongest data, but still faces doubts whether its compound NKTR-214 improves on the profile of Opdivo plus Yervoy (ipilimumab) in treating melanoma.
Phase 2 results disclosed at the conference showed a 53% overall response rate, with a 24% complete response rate — lower than had been observed in earlier data cuts this year, but slightly higher than the 50% revealed in a study abstract.
In a call with investors Saturday, Nektar defended its data and made a positive comparison to the original evidence supporting approval of Opdivo and Yervoy in the skin cancer.
Importantly, NKTR-214 appears to be doing what it's designed to do, activating the immune system and mobilizing immune cells to combat tumors. In patients who tested negative for a biomarker known as PD-L1 — a population known to be less responsive to immunotherapy — 43% responded to NKTR-214 plus Opdivo.
Brad Loncar, a biotech investor who runs a cancer immunotherapy fund, said Nektar's data will "remain a battleground" for investors, giving evidence that enables both "supporters and doubters to walk away entrenched."
One of the key questions moving forward will center on how much evidence drugmakers need to show for each partner drug to justify large combination studies.
For Bristol-Myers and Nektar, that decision's already made; the partners have moved into Phase 3 testing in first-line melanoma and have plans for seven other registrational studies.
But for others, continued questions may cool investor enthusiasm further still.