Merck touts new data for Keytruda combos in NSCLC at North American conference
Merck marched out new data from two studies on Friday to back king Keytruda — the drug that made the Big Pharma $11.1 billion last year — in advanced non-small cell lung cancer (NSCLC).
At the IASLC 2020 North America Conference on Lung Cancer, Merck read out long-term data from Cohort G of its Keynote-021 study, which assessed Keytruda in combination with chemotherapy. It also touted results from a Phase I/II study testing Keytruda and quavonlimab, its anti-CTLA-4 therapy, as a first-line therapy.
The company plans on diving right into a Phase III study with the Keytruda and quavonlimab combo, it announced.
In the Keynote-021 study, patients were given either Keytruda with Eli Lilly’s chemotherapy pemetrexed and platinum chemotherapy, or chemotherapy alone. This particular Keytruda combination was approved by the FDA in 2018 as a first-line treatment in non-squamous NSCLC patients with no EGFR or ALK genomic tumor aberrations.
At a three-year follow-up mark, about half of patients in the Keynote-021 treatment arm were still alive, as opposed to 37% of patients on just chemo, according to Merck. Compared to chemo, the Keytruda cocktail reduced risk of death by 29%, with a mean overall survival of 34.5 months versus 21.1 months, Merck said.
Merck reported a 58% objective response rate for the Keytruda arm, and a 33% rate for the chemo arm. Median progression-free survival was 24.5 months for those on Keytruda versus 9.9 months for those on chemotherapy alone. The Keytruda arm’s median duration of response was more than a year longer than the chemotherapy arm. And 11 of 12 patients —92% — who completed two years of treatment with Keytruda were still alive at year three.
No new safety signals were noted in the follow-up, according to Merck.
As for the Phase I/II study with quavonlimab, Merck reported that results showed an “acceptable safety profile with no unexpected toxicities.” The trial tested various doses of the combination as a first-line therapy, with safety and tolerability as the primary endpoints. Secondary endpoints included objective response rate, progression-free survival, overall survival and duration of response.
Quavonlimab was administered in 25 mg or 75 mg doses every three or six weeks along with Keytruda. About 98% of patients experienced any-grade adverse events, according to Merck. Treatment-related adverse events (TRAEs) occurred in 85% of patients, 36% of which were Grade 3 or higher. The most common TRAEs were increased alanine aminotransferase, pneumonitis, and increased aspartate aminotransferase, Merck said.
Participants who received 25 mg of quavonlimab every six weeks had a median progression-free survival of 7.8 months and a median overall survival of 18.1 months, according to the data. Upon reviewing the data, Merck recommends this dosing for a Phase II study.
Keytruda is approved to treat a variety of cancers aside from NSCLC, including small cell lung cancer, melanoma, head and neck squamous cell cancer, and Hodgkin lymphoma, to name a few. At this year’s ESMO, Merck announced positive Phase III results for Keytruda as a first-line esophageal cancer treatment in combination with chemotherapy.
“Over the last five years, Keytruda has become foundational in the treatment of metastatic lung cancer. The long-term data from Keynote-021 (Cohort G) reinforce the use of Keytruda in combination with chemotherapy in certain advanced lung cancer patients, while data from our oncology pipeline reflect our commitment to exploring a number of new combinations with Keytruda that we believe could have a meaningful impact for more lung cancer patients,” Merck Research Laboratories VP of oncology clinical research Vicki Goodman said in a statement.
Cowen analysts predict Keytruda sales will reach $14.1 billion in 2020, and $21.5 billion in 2025.”However, MRK’s increasing reliance on this product, possibility of significant M&A to diversify revenue, and limited pipeline are risks,” they wrote in a report.
Back in May, Roche’s Tecentriq got the FDA green light to treat newly diagnosed, metastatic NSCLC patients without EGFR or ALK mutations whose tumors have high PD-L1 expression.
“By virtue of being late to market, Tecentriq monotherapy (IMPOWER110) has little chance of gaining significant share in 1L NSCLC despite posting OS similar to Keytruda in PD-L1 high patients,” Cowen analyst Steve Scala wrote in a note that month. “However, that comparable OS benefit may give confidence that any additional efficacy provided by (anti-TIGIT drug) tiragolumab in Phase II will translate to superior performance of the combination in Phase III.”