New data presented at the 2022 American Society of Clinical Oncology (ASCO) annual meeting reaffirm Keytruda’s potential against stage 2 skin cancer, an exec said. In an interview, he reflected on his first ASCO conference—long before the drug was a megablockbuster—and the clinical journey since then.
Scot Ebbinghaus, M.D., vice president of global clinical development for Merck Research Laboratories, was ecstatic to be back at the conference in person after a pandemic hiatus.
More than a decade ago, Merck's clinical program for the med focused on one tumor type, Ebbinghaus said. The research executive entered the scene about a year and a half later, and things have certainly changed for Keytruda since then.
At this year's ASCO meeting, investigators are presenting more than 130 Keytruda abstracts. The company is testing the drug in more than 30 tumor types, with more than 1,700 related clinical trials in the books.
“It's been a tremendous journey,” Ebbinghaus said. “I couldn't be prouder—collectively, it's such a large body of work.”
Approved by the FDA for patients with unresectable or metastatic melanoma, Keytruda also won an approval in December 2021 for the adjuvant treatment of adult and children older than 12 with stages 2B, 2C, or 3 melanoma following complete resection. The designation was based on relapse-free survival (RFS) results from the KEYNOTE-716 phase 3 trial.
Now, a late-breaking abstract data presented Sunday reaffirmed that the treatment cuts risk of melanoma recurrence in distant sites for the same patient population by about 35% compared with placebo.
“It's important to patients, prescribers, regulatory authorities and all stakeholders to show that you can prevent the cancer from coming back at distant sites and that's what we're showing at this ASCO,” Ebbinghaus explained.
The distant metastasis-free survival (DMFS) data followed up with KEYNOTE-716 patients after a median of 27.4 months. For the study, investigators showed that Keytruda delivered statistically significant improvement in DMFS versus placebo. Median DMFS was not reached in either arm.
According to Kaplan-Meier estimates, 81.2% of patients receiving Keytruda were recurrence-free at two years compared to 72.8% of patients on placebo. In the Keytruda arm, 12.9% of patients experienced a DMFS event—the first diagnosis of a distant metastasis—compared to 19.4% of patients receiving placebo.
The safety profile was consistent with previously reported studies. Treatment-related adverse events grade 3 or higher were observed in 17% of patients receiving Keytruda, compared with 5% for the placebo group. Immune-mediated events and infusion reactions were also higher with Keytruda, at 38% versus 9%, respectively.
Also at ASCO, investigators presented detailed subgroup analyses for KEYNOTE-091 in stages 1B to 3A non-small cell lung cancer. Previous analyses of the phase 3 trial offered “convergent validity” that patients can benefit from Keytruda as an adjuvant treatment after surgery, an exec previously said.
At this weekend's meeting, Ebbinghaus highlighted the consistency of the data across subgroups and noted that the trial has read out on its DFS endpoint. The KEYNOTE-716 and KEYNOTE-091 data readouts underscore the idea that there's an important role for Keytruda in early disease, Ebbinghaus said.
Meanwhile, four other trials evaluating Keytruda in patients with earlier stages of cancer have also met their primary endpoints, including KEYNOTE-054 in stage 3 melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; and KEYNOTE-057 in an early stage of bladder cancer.
And that’s not to mention about 20 early-stage trials—made up of 17,000 patients—still left to read out. From one patient participant in 2011 to more than 288,000 in 2022, it’s certainly not early days for Keytruda—but it doesn’t appear anywhere close to the end, either.