Merck Expands Cancer Portfolio Beyond Keytruda with New Therapeutic Approaches

Merck & Co.'s presence in cancer has long rotated around its crown jewel checkpoint inhibitor Keytruda. But with the blockbuster approaching a series of patent cliffs, Merck is writing its next chapter in cancer R&D.

"In our prior era, everything was about Keytruda," said the company's senior vice president and head of translational medicine and discovery oncology. "And in some ways you could argue that Merck wrote the book about PD-1s."

Merck deepened its footprint in the blood cancer market in 2024, spending $700 million to snap up a bispecific candidate from Curon Biopharmaceutical. That same year, the company also invested in T cell engagers and picked up Harpoon Therapeutics, a specialist in the space, in a deal valued at $680 million.

The company has adopted a "one pipeline" approach, by which it considers both external and internal candidates to all be a part of the same pipeline. When hunting for new candidates, Merck has set its sights on a precision oncology strategy for targeted patient populations and candidates it can pair with its existing portfolio.

Keytruda is part of a vast network of clinical trials pairing the immune-targeting therapy with other technologies. Whether the trial involves Merck's own candidates or other companies' drugs, this combination approach is aimed at both improving efficacy and moving into earlier lines of care.

Merck's recent bladder cancer win for Keytruda paired with Pfizer and Astellas' antibody-drug conjugate Padcev demonstrated a 50% reduction in the risk of death. "What happened with Keytruda and Padcev was incredible in late-stage care," the senior vice president said. "But moving it into earlier stages of care could take it from incredible to saving people who would have died."

Merck has zeroed in on three therapeutic approaches that could help define its upcoming era in oncology.

While Keytruda remains Merck's stalwart immunotherapy, the company is developing other candidates that target the immune system, which include a T cell engager dubbed gocatamig. The candidate from Harpoon is being tested in mid-stage trials for lung cancer. Merck also struck a deal in 2024 to co-develop and commercialize gocatamig with Daiichi Sankyo, which will study it in combination with one of its own ADCs in multiple cancer types.

ADCs are front and center in Merck's pipeline of tissue-targeting therapies. One of the company's lead ADCs, sacituzumab tirumotecan (sac-TMT), is in 16 late-stage trials for multiple cancers. The company predicts sac-TMT will be a key growth driver by 2027 with blockbuster potential.

Merck licensed sac-TMT from China's Sichuan Kelun-Biotech Biopharmaceutical and the treatment has racked up multiple clinical wins, including positive late-stage readouts in breast and lung cancer.

Merck's attempted $30 billion buyout of Revolution Medicines, which specializes in RAS-targeting cancer treatments, generated significant buzz this year. Although the deal never went through, Merck already has its foot in the tumor intrinsic door with a therapy that targets KRAS — a mutation in the RAS bucket that's also one of the most frequently mutated oncogenes in cancer, according to Merck.

The company launched a phase 3 trial for its KRAS G12C inhibitor calderasib in non-small cell lung cancer earlier this year after prior trials revealed anti-tumor activity. Calderasib is also being tested in colorectal cancer and in combination with other drugs including Keytruda.

Getting the candidate across the finish line would mark another milestone for the rapidly evolving field of RAS treatments, which notched its first approval in 2021 for a drug targeting KRAS, a mutation once deemed undruggable.