Shares of Merus fell 6% Monday morning as an interim update for a bispecific therapy revealed three deaths in the lung cancer portion of an ongoing trial.
MCLA-129 is being assessed in 60 patients across three expansion cohorts in an open-label phase 1/2 study, with a main goal of improving the overall response rate. The therapy is a bispecific antibody targeting EGFR and c-MET, which are believed to be dysregulated in many tumors such as non-small cell lung cancer.
In one group, the med is paired with AstraZeneca’s Tagrisso in patients with NSCLC. Out of the 60 patients in the lung cancer group, 16 were treated in the first-line setting and were evaluated for a response. All of these patients saw their tumors shrink, according to results presented (PDF) Dec. 2 at the European Society for Medical Oncology's Asia Congress 2023.
There were nine partial responses and three unconfirmed partial responses. Eleven were still ongoing, including the three unconfirmed responses. Merus said the data showed a 94% disease control rate, and the median duration of exposure so far was 5.1 months with 81% continuing treatment.
In the second-line setting, 44 patients were treated and 34 were evaluated. All had previously received Tagrisso either in the first-line setting or the second-line setting, with half receiving it as their only prior therapy and 36% having chemotherapy as well.
Merus reported 11 confirmed partial responses and one unconfirmed partial response, with nine continuing as of the cutoff date including the unconfirmed response. There was a 74% disease control rate and 2.8 months was the median duration of response with 39% of patients continuing treatment.
But the safety data across both cohorts was the headline, with Merus reporting three cases of grade 5 treatment-related interstitial lung disease—meaning three patient deaths.
All patients experienced some sort of side effect deemed "treatment-related," with infusion reactions and nausea being the most common. Twenty-three patients experienced at least one grade 3 or higher adverse event, including the seven cases of interstitial lung disease, but other events included acne, flushing, rash and low blood pressure. There were 13 total cases of ILD across all grades. Merus also reported 14 cases of blood clots, with three considered treatment-related.
Merus said the safety data shows adverse events are associated with EGFR and c-MET inhibition. Fourteen patients discontinued due to treatment-emergent adverse events.
ILD has cropped up in a number of recent cancer trials, including Daiichi Sankyo and AstraZeneca’s latest antibody-drug conjugate effort datopotamab deruxtecan (Dato-DXd). ILD causes scarring of the lungs and can lead to irreversible tissue damage. Daiichi and AstraZeneca reported seven patient deaths earlier this year that were deemed to be drug-related by an independent committee.
At the ESMO Congress in Madrid in October, Daiichi Sankyo and AstraZeneca dug into the safety data and showed that more patients with lung cancer experienced the side effect than in a similar study with Dato-Dxd for breast cancer. The conclusion was that the nature of the damage to the lungs coming into the trial might put a person at greater risk of the adverse event.
Merus also reported data for MCLA-129 (PDF) in head and neck squamous cell carcinoma at the ESMO Asia Congress 2023, which showed no cases of ILD or deaths. Of 22 evaluable patients, infusion-related reactions occurred in 16 people, while skin toxicity was observed in 19. There were six total grade 3 or higher adverse events, with three cases of skin toxicity.
Merus CEO Bill Lundberg, M.D., pledged to be fiscally responsible with the program's next steps while still suggesting the MCLA-129 program would go ahead.
“MCLA-129 is a very active drug in EGFRm NSCLC and we’re planning a focused investment to evaluate MCLA-129 in combination with chemotherapy, which we expect to start early in 2024,” Lundberg said. “We are in a fortunate position to have a strong balance sheet. We also recognize the importance of being responsible with our resources to maintain financial strength, as we plan to initiate a phase 3 trial of petosemtamab in [second-line-plus] HNSCC by mid-2024.”
At ESMO's previous meeting in Madrid, Merus showcased the NRG-1 fusion tumor bispecific antibody zenocutuzumab (Zeno) in pancreatic cancer. Zeno led to a 42% response rate with one patient achieving a complete response and 13 notching a partial response. Merus also reported a 72% clinical benefit rate and 82% of the patients saw tumor reduction. The safety profile was dubbed “extremely well tolerated” but detailed information was not provided.
Merus’ shares fell to $22.67 around 11 am ET on Monday, before settling around $23.58, or down just over 6% around mid-day. The company opened at $25.10.