For many cancers now, the standard treatment is chemotherapy plus an immunotherapy such as Merck's Keytruda, the best-selling drug in the world. But many patients eventually relapse and Keytruda patents start peeling off in 2028.

What's the next standard treatment?

Many think it will pair two innovations: precisely-targeted chemo drugs known as antibody-drug conjugates, or ADCs, and augmented immunotherapies in the form of bispecific antibodies.

There's hardly a cancer drug company that isn't working on one of these next-generation products. Bispecific antibodies are being tested by Bristol Myers Squibb (with its partner BioNTech), AstraZeneca, and the biotech firm Summit Therapeutics. ADCs have already rung up big sales for Astra, Pfizer, Gilead Sciences, and Roche Holding, but Merck has a strong contender in development.

Immunotherapies, such as Merck's Keytruda and Bristol's Opdivo, are antibodies that foil a ruse used by cancer cells to disarm the immune system. Cancer cells display a "stand-down" signal called PD-1 that tells immune cells to leave them alone. By blocking PD-1 signaling, immunotherapy drugs reopen the cancer to immune attack.

The PD-1 immunotherapies have been wildly successful products. Sales of Keytruda last year were $32 billion, while Opdivo's sales were $10 billion. They have prolonged survival across the landscape of cancer; Keytruda is approved for 45 indicated uses.

While the PD-1 drugs prolong patients' survival, many eventually relapse. Bispecific antibodies are one strategy to improve on the PD-1 achievement, since they can combine an immunotherapy with another cancer-fighting mechanism.

Bispecifics with multiple cancer-targeting prongs are already on the market for treating blood cancers, from the likes of Amgen, Johnson & Johnson, Roche, AbbVie, and Regeneron Pharmaceuticals. Now, several firms are testing whether immunotherapy bispecifics can improve survival with more common solid tumors, such as lung cancer, breast cancer, colorectal cancer, and melanoma skin cancer.

AstraZeneca is conducting Phase 3 trials of bispecifics against several solid tumor cancers, as is the Bristol-BioNTech team. But one of the most closely-watched trials is being run by Summit Therapeutics.

Later this year, Summit will report results from a global Phase 3 trial of the bispecific antibody ivonescimab in patients with lung cancer. Licensed from the Hong Kong-listed Akeso, ivonescimab combines a PD-1 prong with a prong that works like the off-patent Roche drug Avastin to inhibit the VEGF protein that tumors use to form blood vessels. Combining PD-1 and VEGF in a single bispecific triggers fewer side-effects than using standalone PD-1 and VEGF drugs in combination.

Ivonescimab is already approved and treating patients in China, after Akeso studies showed that it prolonged survival when compared with standard PD-1 immunotherapy and chemo. The Summit results will be the first global test of a PD-1/VEGF bispecific -- with a number of other developers in hot pursuit.

"We're looking to replace the PD-1 component of the equation," says Summit's strategy chief Dave Gancarz. "ADCs are looking to replace the chemotherapy component."

Antibody-drug conjugates, or ADCs, link an antibody to a chemo drug. The antibody is designed to home in on cancer cells, where it deposits its toxic chemo payload. That can spare normal cells from the damage they suffer from when standard chemotherapy toxins course through the whole body.

"The concept is a guided missile," says Eliav Barr, the chief medical officer at Merck Research Laboratories. The antibody targets markers found on the surface of cancer cells, which then absorb the toxic payload.

A number of ADCs have been approved in recent years. Enhertu brought in $5 billion in sales last year for AstraZeneca and its partner Daiichi Sankyo, targeting breast and lung cancers that display a protein called HER2. Sales of Roche's Kadcyla and Pfizer's Padcev were each about $2 billion in 2025.

Some of the most promising ADCs target a protein called TROP2 that's found on many solid tumors. A TROP2-targeting ADC called Trodelvy used to treat breast cancer generated sales of more than $1 billion last year for Gilead.

Merck is running 18 clinical trials for a TROP2 ADC called sac-TMT, which it licensed from the Hong Kong-listed Kelun-Biotech. Many of the trials use the ADC with Merck's Keytruda. The studies will yield their data over the next few years, hopefully positioning sac-TMT for approval just as Keytruda loses its patent protections.

Merck does have bispecifics that Barr says are "Phase 3 ready." He says it will be important to see whether PD-1/VEGF bispecifics like the Summit product meaningfully extend patients' healthy survival in their Phase 3 trials.

Barr says these next-generation cancer regimens could offer longer survival with less toxicity, by combining bispecific "Sons of Keytruda" with ADC chemotherapies.

Write to Bill Alpert at william.alpert@barrons.com

This content was created by Barron's, which is operated by Dow Jones & Co. Barron's is published independently from Dow Jones Newswires and The Wall Street Journal.

(END) Dow Jones Newswires

July 20, 2026 02:00 ET (06:00 GMT)

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