Each year, the American Association for Cancer Research’s conference spotlights promising early research into new approaches for attacking tumors. This year’s meeting, held in person after two years of being hosted virtually, is no different.
Over the weekend, trial investigators presented new data for immunotherapies and for cell therapies — two types of cancer medicines that have captured the lion’s share of research and development dollars over the past decade.
Researchers discussed early treatment with Bristol Myers Squibb’s drug Opdivo, as well as a new immunotherapy target being explored by Merck & Co., Roche and Gilead. In cell therapy, presentations on a treatment that uses NK, rather than T, cells drew attention, as did early data for a BioNTech treatment that pairs CAR-T therapy with an mRNA vaccine.
Read on for more on four of the most notable datasets at this year’s AACR:
Another immunotherapy step into early lung cancer
Cancer immunotherapy has changed the way doctors treat metastatic lung cancer. Now drugmakers are focusing on earlier settings, testing whether adding immunotherapy to drugs given before or after a tumor is surgically removed can have a similarly significant impact.
The FDA recently approved two such regimens, involving immunotherapies from Bristol Myers and Roche, for non-small cell lung cancer and a third, from Merck, could soon be submitted to U.S. regulators. Study results have shown all three can delay the return of cancer longer than chemotherapy alone.
However, Bristol Myers’ Opdivo is the only one tested for a short, nine-week course before surgery, rather than a longer course afterwards. While comparing trials can be difficult, the 37% reduction in the risk of relapse or death that Bristol Myers reported in its Phase 3 trial is meaningfully higher than what the others have shown. As a result, some experts have questioned whether immunotherapy is more effective before surgery, when more of a tumor is still present, than after.
On Monday at AACR, Bristol Myers revealed additional details from its trial, called Checkmate-816 and newly published in The New England Journal of Medicine. The results “are expected to be practice changing,” wrote Christine Lovly, the co-leader of the translational research and interventional oncology research program at the Vanderbilt-Ingram Cancer Center, in an accompanying editorial.
The findings still leave important questions to answer, Lovly noted. One is whether the study proves that so-called pathological complete responses — the absence of any signs of a tumor on a scan — is a marker for a drug’s ability to keep cancers from returning. Another is whether delaying recurrence in lung cancer improves survival, something Bristol Myers’ data does not currently prove.
Logistical challenges are ahead as well. Patients with EGFR or ALK mutations — well-known genetic drivers of lung cancer — were excluded from Bristol Myers’ study, meaning biomarker testing upon diagnosis will have to become standard in early lung cancer. That would represent “a considerable alteration in the routine practice of lung cancer medicine,” she wrote. Moreover, administering treatment will require multi-disciplinary teams that many treatment centers don’t have, which may widen “survival gaps” that already exist.
“How can these cutting-edge treatments be implemented broadly,” Lovly asked, “so that all patients may have access to potentially life-saving therapies?”
Promise for a new lymphoma treatment
Over the past two years, drugmaker interest in a new type of cell therapy involving natural killer cells has steadily grown. These NK cell therapies, as they’re known, are meant to be safer alternatives to the T cell-based treatments used to treat certain blood cancers.
Some of that excitement is due to a first-of-its-kind program from the MD Anderson Cancer Center and German biotech Affimed. The treatment uses NK cells harvested from cord blood alongside an experimental Affimed antibody drug that helps those cells recognize a protein on tumors called CD30. A Phase 1 study in patients with lymphoma produced encouraging results, and without the severe side effects commonly associated with the CAR-T treatments from Novartis, Gilead and Bristol Myers.
New results presented at AACR showed that 13 lymphoma patients whose disease progressed despite a median of seven other treatments responded to the dose Affimed selected for further study. Eight of those patients experienced remission, while the remaining five had partial responses. Notably, the 63% complete response rate is better than what was disclosed in December, when only five patients were in remission. There were still no instances of the immune side effects commonly associated with CAR-T.
Still, it’s not known how long those remissions will last and how the drug’s overall profile will compare to CAR-T. While seven of the patients remained in remission for at least five months, and two have been cancer free for as long as 10 months, the follow-up time is “too short to assess durability,” wrote Stifel analyst Bradley Canino.
The regulatory path forward is also unclear. The program will now transition from MD Anderson to Affimed. The biotech is still figuring out the optimal number of treatment “cycles” for patients, as well as whether the antibody drug could be used as a maintenance therapy on its own. Affimed expects to meet with the Food and Drug Administration later this year, Canino wrote.
Questions on a cancer drug target
Immunotherapies aimed at a protein called TIGIT are some of the most closely watched in cancer research, due to encouraging early results showing they might boost the effects of other drugs. That hypothesis took a hit last month when Roche’s top prospect, tiragolumab, failed its first Phase 3 trial in a tough-to-treat form of lung cancer. The results could temper expectations for TIGIT drugs, which are being advanced by many drugmakers, including Merck, Gilead and GlaxoSmithKline.
The narrative won’t change at AACR. Still, new study results from Merck in ovarian and cervical cancer help make the case that “TIGIT is clinically relevant and has potential” beyond non-small cell lung tumors, where it’s shown the most promise, according to Daina Graybosch, an analyst at SVB Leerink.
Merck’s drug vibostolimab, when used alongside the company’s other immunotherapy Keytruda, produced better response rates than Keytruda has alone in ovarian and cervical tumors, Graybosch wrote in a note to clients. That finding suggests TIGIT drugs might broaden the reach of immunotherapies into tumors that are less responsive to those types of drugs.
The results were somewhat perplexing, however. The drug performed best in cervical cancer patients who had no PD-L1 on their tumors, as well as in ovarian cancer patients with high PD-L1 levels. Overall results were also comparable to what’s been observed in prior tests of Keytruda, raising questions of whether the subgroup findings were just statistical “noise,” Graybosch wrote.
More definitive answers about TIGIT’s potential in ovarian and cervical tumors will come when Roche delivers results from a Phase 2 trial called SKYSCRAPER-04 later this year. Data from a Phase 3 study in a common, more treatable form of lung cancer, meanwhile, are expected even sooner. Until then, Merck’s results “leave room for debate and doubt” about TIGIT, Graybosch wrote.
A solid tumor advance for CAR-T
Long before BioNTech developed one of the most widely used vaccines for COVID-19, the German biotech was focused on making cancer immunotherapies.
Over the weekend at AACR, that work was back in the spotlight as researchers presented study results for one of BioNTech’s experimental cancer medicines. The treatment consists of a CAR-T therapy made from patient immune cells, paired with an mRNA vaccine encoding for the same protein targeted by the cell therapy.
The combination approach is designed to help the cancer-fighting CAR-T cells expand and persist in the body after their infusion, and potentially solve a limitation that has prevented CAR-T therapies from successfully treating solid tissue tumors.
“Our preliminary data indicate that the successes of CAR-T in hematological cancers may indeed be transferred to solid tumors,” said BioNTech CEO Ugur Sahin, in a statement.
BioNTech’s data comes from 16 patients with cancers expressing a protein known as Claudin-6 that’s commonly found in testicular, ovarian and endometrial tumors.
Six of 14 evaluable patients responded to treatment, including one who went into remission. Four of those responses were in patients who received the CAR-T as well as the mRNA vaccine. (Some only received the CAR-T.)
The small number of patients involved and lack of a control arm means determining relative benefit is difficult, while limited follow-up makes judging the durability of treatment effect harder.
Side effects were common, although those typically associated with CAR-T treatment were classified as less severe and “manageable,” according to BioNTech. Two dose-limiting toxicities were reported, one of which occurred prior to administration of the mRNA vaccine.
Further data from the study will be presented later this year.
