The checkpoint inhibitor improved patient outcomes in three cancer trials, according to results presented at the AACR meeting.
Pictured: Abstract keys. © Nicole Bean/ BioSpace, Inc.
Merck presented positive results for its anti-PD-1 therapy Keytruda (pembrolizumab) as a first-line treatment for advanced biliary tract cancers and metastatic desmoplastic melanoma, a rare type of skin cancer, at the American Association for Cancer Research (AACR) 2023 Annual Meeting. And in combination with a personalized mRNA-based cancer vaccine, Keytruda improved survival in patients with high-risk melanoma.
“We are pleased to share progress in these trials, with data demonstrating the impact and continued importance of Keytruda in both established areas and in potential new settings through combinations,” Eric Rubin, senior vice president of oncology early development for Merck Research Labs, told BioSpace in an e-mail.
Keytruda Reduces Risk of Death from Biliary Tract Cancer
In combination with chemotherapy drugs gemcitabine and cisplatin, Keytruda significantly improved overall survival (OS) compared to chemotherapy alone in patients with biliary tract cancer (BTC), according to the results of the Phase III KEYNOTE-966 clinical trial.
BTC is a rare type of cancer that develops in the bile ducts and gallbladder. The disease is often diagnosed at an advanced stage, and there are few good treatment options. As a result, the prognosis is typically poor: Just 10% of patients survive five years after diagnosis, according to the American Cancer Society.
“Advanced biliary tract cancers are cancers with rising incidence and very poor prognosis in need of new treatments,” Robin “Katie” Kelley, a professor of clinical medicine at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, who led the trial, told BioSpace.
In the 1,069-patient trial, individuals with metastatic or unresectable BTC were randomly assigned to receive gemcitabine and cisplatin alone or in combination with Keytruda. Patients receiving the checkpoint inhibitor showed a mean increase in OS of 1.8 months.
After a median follow-up of 25.6 months, patients treated with Keytruda had a 17% lower risk of death than patients who received chemotherapy alone.
“We hope that future studies on blood and tumor tissue samples from patients enrolled on KEYNOTE-966 will help us to identify features of tumors most likely to benefit as well as additional treatment strategies to further improve outcomes,” Kelley said.
Keytruda Improves Responses in Patients with Rare Skin Cancer
Keytruda improved clinical responses in patients with unresectable metastatic desmoplastic melanoma, a rare type of skin cancer, according to a prospective Phase II S1512 clinical trial.
The drug is approved for the first-line treatment of patients with unresectable metastatic melanoma, but its effectiveness in patients with the desmoplastic subtype had not been assessed.
Of 27 patients with unresectable metastatic desmoplastic melanoma who were given KEYTRUDA every three weeks for two years, 89% demonstrated a clinical response, including 33% complete responses.
The results demonstrate “an extraordinarily high response rate in a rare subtype of metastatic melanoma that often occurs in elderly patients in sun-exposed areas,” Justin Moyers, a medical oncologist at the Angeles Clinic and Research Institute who was not involved in the trial, told BioSpace.
“This represents a step forward in personalized immunotherapy that allows for de-escalation from dual-agent checkpoint in the first-line setting,” Moyers said.
Regarding safety, the company reported that 25% of patients experienced a serious adverse event.
The researchers plan to evaluate Keytruda’s long-term efficacy, including overall survival and progression-free survival.
Combining Keytruda with Cancer Vaccine Prolongs Survival of Melanoma Patients
Merck and Moderna’s mRNA-based cancer vaccine mRNA-4157/V940, in combination with Keytruda, demonstrated an increase in recurrence-free survival in patients with high-risk melanoma compared with Keytruda alone. The vaccine targets neoantigens, tumor-specific proteins generated by mutations in cancer cells.
“The revelation that clinically important immune responses depend on recognition of neoantigens has driven the idea that you should vaccinate people against neoantigens,” presenting author Jeffrey Weber, deputy director of the NYU Langone Perlmutter Cancer Center and Laura and Isaac Perlmutter Professor of Oncology at NYU Grossman School of Medicine, told BioSpace.
In the Phase IIb KEYNOTE-942 trial, 157 patients with stages IIB/IIIC/IIID and IV melanoma were randomly assigned to receive either Keytruda alone or in combination with mRNA-4157/V940. After 18 months of combined treatment, administered at three-week intervals, patients experienced a 44% reduced recurrence or death compared to Keytruda alone.
The vaccine was effective regardless of tumor mutational burden and did not increase the risk of adverse effects.
“It has applicability way beyond melanoma,” said Weber. “Theoretically, any tumor that has some sensitivity to PD1 blockade, such as renal cell carcinoma and triple-negative breast cancer, would be ripe for a vaccine strategy.”
Rubin said Merck and Moderna will initiate a Phase III study in patients with adjuvant melanoma in 2023 and “rapidly expand to additional tumor types, including non-small cell lung cancer.”
Holly Barker is a freelance writer based in London. She can be reached on her website.
