Pfizer, AstraZeneca, Merck bet on chemo replacement

Chemotherapy has long been a cornerstone of cancer treatment, saving millions of lives.

But the pharmaceutical industry says a popular class of targeted cancer therapies could one day replace chemotherapy and its potential for harsh side effects. Antibody-drug conjugates (ADCs) have taken major strides in recent years, as companies including AstraZeneca, Daiichi Sankyo, Pfizer and Merck are developing drugs in the space that could ease the trials of cancer treatment and make them big money in the process.

Drugmakers have poured billions of dollars into developing ADCs. The medicines are designed to deliver potent chemotherapy directly to cancer cells while sparing surrounding healthy cells. That’s unlike traditional chemotherapy, which can affect both types of cells.

But it will likely take years before ADCs can replace chemo, and some outside cancer experts say the pharmaceutical industry still has more work to do to refine the treatments.

“I think we’ve had some successes in the space, but I think the early hopes that they would sweep away the need for chemotherapy have mostly been unfulfilled so far,” Dr. John Heymach, chair of thoracic/head and neck medical oncology at MD Anderson Cancer Center, told CNBC. “There’s clearly room for improvement.”

Still, some companies say ADCs have shown the ability to replace chemotherapy in certain settings. Other drugmakers say they are inching closer to developing ADCs that can be used before chemo — or at the very least, learning from previous missteps.

“We are leading the way towards establishing ADCs as a precision-based approach to replace classic chemotherapy,” David Fredrickson, executive vice president of AstraZeneca‘s oncology business, told CNBC. 

He was in part referring to AstraZeneca’s promising data shared at the 2025 American Society of Clinical Oncology annual meeting in Chicago, where several other companies also delivered positive results on existing and experimental ADCs – or even data that could lead to new standards in cancer care.

Since the first ADC hit the market in 2000, the field has made major progress. More than a dozen ADCs are now approved in the U.S., and some have become a preferred or commonly used treatment option for specific tumors. Hundreds more ADCs are in development. Large pharmaceutical companies have scooped up many of the approved and experimental ADCs in massive deals, such as Pfizer‘s $43 billion acquisition of Seagen in 2023.

A range of drugmakers want in on the hype, and for good reason. ADCs could account for $31 billion of the $375 billion worldwide cancer market in 2028, according to estimates from the drug market research firm Evaluate.

ADCs still pose major challenges. Among them, some treatments can release the toxic chemotherapy “payload” into the bloodstream too soon, affecting healthy cells and causing a range of side effects. Some health experts say drugmakers also need to identify the right cancer-causing proteins to target and new payloads for these drugs.

The pharmaceutical industry is working to overcome these issues by developing next-generation ADCs and combination regimens. Some ADCs, such as a newly approved therapy from AbbVie, target new proteins, while others use new so-called linker platforms that better control when and where the toxic payload is released.

“It’s been hard. We haven’t optimized everything perfectly yet. But I think that the field is still growing fast, and it’s making improvements every year,” said Dr. Jeffrey Infante, global head of early clinical development, translational research and oncology at Johnson & Johnson, which has several experimental ADCs.

Most ADCs consist of three components: an antibody that targets a protein found in high amounts on the surface of cancer cells, a chemotherapy payload and a linker that connects them. The antibody guides the ADC to the cancer cell, and once inside, the linker releases the chemotherapy to kill the cancer from within.

Newer ADCs leading the space, such as Enhertu from AstraZeneca and Daiichi Sankyo, improve on that design and are moving closer to becoming standard treatments for certain cancers.

Enhertu delivers more chemotherapy per dose than older ADCs and uses a smart linker designed to release the drug only inside tumors. It can also kill nearby cancer cells with lower levels of HER-2, the protein it targets – a major milestone in oncology. 

Enhertu is approved in the U.S. to treat certain breast, lung and gastric cancers, with 2024 sales from both companies topping $3.7 billion. New data presented at ASCO could expand Enhertu’s use and shift how breast cancer is treated for the first time in a decade. 

Enhertu stalled the growth of a common type of breast cancer by over a year in a late-stage trial when used as an initial treatment, and compared to a standard regimen containing chemotherapy. The study combined Enhertu with a medicine called pertuzumab as a first option for patients with HER-2-positive metastatic breast cancer. AstraZeneca and Daiichi Sankyo are seeking approval for that use. 

“We’re moving this drug earlier and earlier, and the magnitude of benefit gets bigger and bigger,” said Ken Keller, Daiichi Sankyo’s CEO and head of oncology business. “The hope is that we can move it into earlier-stage settings where curing is the goal.”

Keller said the results and previous Enhertu data show “you can replace and knock the chemotherapy out.” The companies also plan to release data on a subset of patients in the study who took Enhertu alone.

MD Anderson’s Heymach said the data “is the type of clear, major advance that we’d like to see more often, where this ADC could become the first option for patients.”

Other ADCs are advancing, too.

Pfizer’s Adcetris, which it acquired from Seagen, is approved as an initial treatment with chemotherapy for certain lymphomas. It raked in almost $1.1 billion in sales in 2024.

Padcev from Pfizer and Astellas Pharma is approved with Merck’s Keytruda as a first-line bladder cancer therapy, and booked $1.69 billion in sales last year. Keytruda is a blockbuster immune checkpoint inhibitor that blocks a protein called PD-1, helping immune cells more effectively recognize and kill cancer cells. 

Gilead‘s Trodelvy, an ADC that took in $1.3 billion in revenue in 2024, also turned heads at ASCO. 

As a first-line treatment, Trodelvy combined with Keytruda lowered the risk of disease progression by 35% in patients with an aggressive type of breast cancer in a late-stage trial. The study examined patients with advanced triple-negative breast cancer whose tumors express PD-L1.

“What these studies demonstrate is that if you replace the chemotherapy with the antibody drug conjugate, then you do get improved efficacy and improved safety,” said Dr. Dietmar Berger, Gilead’s chief medical officer. 

Berger said there are early signs that the combination may also help patients live longer, but the data is still new. Gilead is also studying Trodelvy as a first-line treatment in another type of breast cancer and non-small cell lung cancer. 

The ASCO data was a win for Gilead after recent setbacks for Trodelvy. 

In October, Gilead pulled Trodelvy from the bladder cancer market in the U.S. after disappointing results in a trial meant to confirm its benefit. In January 2024, Trodelvy failed a phase three trial in non-small cell lung cancer. 

Berger said that’s one challenge of developing ADCs: effectiveness can vary by cancer type, so some patients may benefit from a drug more than others. 

“You need to learn from the different studies and see the exact populations that might benefit,” Berger said, adding that developing across cancers isn’t “linear.”

British drugmaker GSK is learning from its missteps, too. The company pulled its blood cancer ADC, Blenrep, from markets worldwide in 2022 after it failed a study meant to verify its benefit.

But Blenrep is now reapproved in the U.K., with a U.S. decision due on July 23. 

GSK’s Chief Commercial Officer Luke Miels said the company had to “go back to the drawing board” to revive Blenrep, which involved building a team with deeper ADC expertise and reevaluating dosing.

Blenrep, when combined with other therapies, has since succeeded in two key studies in previously treated blood cancer patients. Under its original approval, it was used on its own. GSK also presented data at ASCO showing Blenrep’s main side effect – blurred vision in about 1 in 3 patients – is reversible and manageable with lower or spaced-out dosing. 

The company expects up to £3 billion ($3.97 billion) in peak annual Blenrep sales. It is also studying the drug as a first-line treatment, which could add to that revenue forecast, Miels said.

Meanwhile, Merck and Daiichi Sankyo face a new hurdle for a drug they are developing.

In May, they withdrew their U.S. application for an ADC targeting HER-3 after it failed to extend overall survival in a late-stage lung cancer trial.

They scrapped the application even though the ADC met the study’s main goal last year: delaying tumor progression compared to chemotherapy in patients previously treated for a certain non-small cell lung cancer.

The drug is one of three ADCs that Merck is co-developing with Daiichi Sankyo as it prepares for Keytruda’s upcoming patent expiration. 

Marjorie Green, Merck’s head of oncology global clinical development, said the companies are learning from “what worked and what didn’t” and still fully investing in refining the drug, with plans to test it in late-stage breast cancer trials.

Other companies are trying to make waves in the ADC space with new approaches to the drugs.

AbbVie, for example, is successfully developing ADCs with new cancer-causing protein targets. The company in May scored U.S. approval for the first-ever ADC targeting a protein called c-Met, which can be found in high levels in non-small cell lung cancer and is associated with a low likelihood of recovery or improvement. 

But the company also released several trial results on a next-generation product that could become a best-in-class c-Met ADC, said Pedro Valencia, the company’s vice president of solid tumor pipeline strategy and execution. He called it the result of years of fine-tuning the company’s ADC platform to “get to that sweet spot.”

AbbVie also released data on its ADC targeting SEZ6, a unique protein that is overexpressed in neuroendocrine tumors such as small-cell lung cancer but not in normal tissue, Valencia said. That ADC has demonstrated response rates that are two to three times more than chemotherapy in those tumors, he said.

Meanwhile, Bristol Myers Squibb is developing a bispecific ADC, said the company’s Chief Medical Officer Samit Hirawat. Those are designed to target two different proteins, or parts of a protein, on cancer cells to make the drug more precise and effective. 

Through a partnership with Chinese company SystImmune, Bristol Myers Squibb is developing a drug that hits EGFR and HER-3, both common in multiple cancers. 

Hirawat said the drug carries more chemotherapy per dose than older ADCs and uses a linker that appears to help avoid a common side effect of rival treatments called interstitial lung disease, a group of conditions that cause lung scarring. A phase three trial is underway in triple-negative breast cancer, with more late-stage studies planned.

Hirawat said the company is also exploring non-chemotherapy payloads to improve efficacy and safety. That includes protein degraders, which eliminate cancer-causing proteins instead of blocking them.

Eli Lilly is also developing ADCs with non-chemotherapy payloads, said Jake Van Naarden, president of Lilly Oncology. He said new types of payloads could help patients who relapse on existing ADCs, shrinking their “newly growing cancers” again in “a durable way.”

Dr. Jennifer Suga, co-chair of Kaiser Permanente’s National Lung Cancer Program, said developing alternative payloads will be crucial, as cancer cells may become “resistant” to those used in current ADCs.

Eli Lilly is also using linker technology from Mablink, acquired in 2023, to help its ADCs stay in the body longer and reach tumors more effectively. 

At ASCO, Eli Lilly released the first human data on an ADC that uses that linker and targets folate receptor alpha, a protein commonly found in ovarian cancer. AbbVie’s approved ADC, Elahere, already targets that protein. 

But Eli Lilly hopes its drug can have fewer side effects, Van Naarden said. In the early trial, the company did not observe any eye-related effects linked to other ADCs. 

J&J hopes to stand out by focusing on prostate cancer, where it has deep expertise.

The lead ADC J&J acquired from the Ambrx targets PSMA, a protein common in prostate tumors. There are currently no approved ADCs with that target. Infante said that ADC has a “very stable” linker platform and can be paired with an existing diagnostic test, allowing the company to easily identify eligible patients for the drug. 

Chemotherapy likely won’t disappear entirely and could still offer “major benefits” as a later treatment option in some cases, according to MD Anderson’s Heymach. But he and drugmakers expect more ADCs will be used to treat solid tumors – cancers that form as masses in organs like the lungs, breasts or ovaries – before chemotherapy over the next decade. 

Heymach said “more effective combinations” of ADCs and other drugs could help establish more ADCs as go-to treatment options across a wider range of cancers.

Pfizer believes immune checkpoint inhibitors such as Keytruda are a particularly promising match for its ADCs, said the company’s Chief Scientific Officer Chris Boshoff. 

Pfizer’s ADCs, built on its vedotin platform, do more than just kill tumor cells. Boshoff said they also trigger immunogenic cell death – a process that sends distress signals to alert the immune system and train it to recognize and attack similar cancer cells.

That sets the stage for checkpoint inhibitors to do their job even more effectively, which is to release the “brakes” on the body’s immune system and help it mount a stronger attack on cancer. Together, they create a one-two punch: ADCs kill the cancer and sound the alarm, while checkpoint inhibitors enable the immune system to fully attack. 

“When we combine them, we see increased response rates, increased progression-free survival, and in the cases where we have tested, an increase in overall survival,” Boshoff said, referring to measures of cancer treatment effectiveness. 

At ASCO, Pfizer shared early but encouraging data on two vedotin-based ADCs in combination with Keytruda. That includes one targeting a protein commonly found in lung cancers called integrin B6, and another targeting PD-L1. Boshoff said the results support starting late-stage trials this year on those combinations in certain cancers. 

Pfizer is also betting on a combination ADC approach with a drug it gained the rights for through a licensing agreement with Chinese company 3SBio: a bispecific antibody drug targeting PD-L1 and VEGF.

BioNTech is banking on a similar combination approach with its bispecific antibody drug that targets those same two proteins. Bristol Myers Squibb in June said it will pay $1.5 billion in upfront fees to co-develop that product. 

BioNTech in April released the first early data to back that combination approach, but will also have to prove each of its four ADCs as solo treatments in trials, said Chief Commercial Officer Annemarie Hanekamp. 

She said BioNTech believes ADCs could take the place of traditional chemotherapy. But the company also hopes its bispecific antibody drug could serve as an improved version of immunotherapies that only target PD-1, such as Keytruda and Bristol Myers Squibb’s Opdivo. 

“We can then combine these two powers together and that’s truly exciting,” Hanekamp said, noting that BioNTech has multiple trials on the combination approach ongoing.

At J&J, Infante said the company plans to be the first to test an ADC in combination with one of its T-cell engagers – a type of immunotherapy that directs immune cells to recognize and kill cancer cells. The company is preparing to start enrolling patients in trials on that combination regimen, he said.