#ASCO21: Merck tacks on armor in early-line cancer fight with 2 Keytruda wins setting the tone
With more and more PD-(L)1 checkpoint inhibitors flooding the market, there has been a long-running war over which of those drugs can secure a lead in early-line patients. With Keytruda on top of the world, Merck is well-positioned to take the lead — and it’s rolling out a pair of studies targeted directly at that front.
As part of a broad plan of attack to bring I-O wonder drug Keytruda into earlier lines of metastatic cancer, Merck will unveil winning results at this year’s ASCO from Phase II and Phase III tests as part of combination therapies topping standard of care in non-small cell lung and gastric cancers.
First, a combination therapy of Keytruda and standard-of-care Herceptin plus chemotherapy posted a confirmed overall response rate of 74% compared with 52% for placebo+SOC in first-line patients with HER2-positive gastric or gastroesophageal cancer, according to data from the Phase III KEYNOTE-811 study.
It’s the first conference presentation for KEYNOTE-811, worth pointing out as the FDA already granted the combination an accelerated approval earlier this month. The complete response rate for the combo was 11.3% compared with 3.1% with a median duration of response of 10.3 months compared with 9.6 months, respectively. Meanwhile, the combo’s safety results were comparable with standard of care with no new safety flags.
The data are a bit after the fact with the approval in hand, but Merck Research Labs CMO Roy Baynes told Endpoints News the results are part of an escalating battle among drugmakers to bring I-O medicines into earlier and earlier lines of therapy. For Merck, that strategy hinges around the use of combination therapies for Keytruda, which have shown a lot more promise than substituting monotherapy for established standard of care in terms of tumor response.
“What you’re seeing is oftentimes in the combinatorial setting, the biomarker becomes less important, response rates are oftentimes quite a lot higher, and we’re often able to address populations that generally were not necessarily benefiting maximally from monotherapy,” he said.
At ASCO, Merck will also present data from KEYNOTE-799, a Phase II study of Keytruda plus platinum-based chemotherapy and radiotherapy in first-line, locally advanced stage III non-small cell lung cancer patients whose tumors can’t be surgically removed.
The current standard of care in that setting is chemoradiation followed by a “consolidation regimen” of AstraZeneca’s Imfinzi. Up to 30% of those patients cannot complete the Imfinzi regimen, offering a big unmet clinical need.
According to early results, the Keytruda combo posted a overall response rate around 70% across two cohorts of patients with either squamous or non-squamous NSCLC receiving two separate chemoradiation regimen plus Keytruda or Keytruda alone. The combined complete and partial responses in Cohort A were 79 and 72 in Cohort B. The duration of response rate after 12 months was 80% and 76%, respectively.
Most importantly on the safety front, the combination of chemoradiation and Keytruda didn’t spur a high rate of pneumonitis — or lung inflammation — in the patient population, Baynes said. Both therapies taken alone have been tied to pneumonitis, and investigators closely monitored patients to see how that safety flag would progress.
With proof-of-concept secured, Merck is also chasing a Phase III study for Keytruda on top of chemoradiation followed by either Keytruda alone or in combination with PARP inhibitor Lynparza as part of the KEYLYNK-012 study.