Fireside Chat: Eliav Barr

Session Focus

Gerberry opened from the commercial reality that every success story has an expiry, including Keytruda, and that Merck is investing heavily behind antibody-drug conjugates. The conversation covered what differentiates one ADC from another, why Merck runs so much clinical work in China, the personalized cancer vaccine program with Moderna, and the trial design problem created by moving into curative settings.

Not Every ADC Is the Same

Barr’s opening point was that ADCs have become prominent, and the field has learned that category membership tells you little. Even within a single target class such as TROP2, there are profound differences in the antibody, the linker and the payload, and all three require attention.

For sacituzumab tirumotecan specifically, Merck had two sources of insight: extensive data from its partner Kelun and their work in China, and an understanding of the strengths and weaknesses of other TROP2-targeted ADCs.

The design differences he named were where the linker connects, the fact that payload release happens in the lysosome, the internalization behavior and the nature of the antibody.

But he was clear about what actually convinced him as a clinician: the phase one results. The molecule showed extraordinary activity across a broad range of tumor types with a tolerability profile that could make it a cornerstone ADC across many regimens. The mechanistic design mattered, and it was the connection to the data that made the case.

What China Offers and What American Centers Miss

Ryan asked directly what Merck gets from Chinese sites that it does not get in America, and how American academic medical centers could better meet the company’s needs.

Barr set the regulatory advantages aside to answer the question asked. The difference he identified is mindset.

Chinese sites, including the most academically excellent among them, enroll large numbers of patients. Their orientation is toward understanding the drug itself rather than toward a local investigator’s own line of research, where the pattern is taking 20 patients for a specific mechanistic question.

The benefits follow. Their view is that running phase three trials is how drugs reach Chinese patients, which is what matters for their mission. They come to know the drug very well and can make observations that genuinely shape its development. And authorship rights follow.

His message for American cancer centers was pointed. The mission is improving cancer care not in 20 years but in five and in three. Doing that requires choosing your drugs and then participating in a big way, which is how a center makes a significant contribution to developing a drug for the American patient in the American context. Merck spends so much time in China, he said, because the sites are genuinely oriented that way and have organized, pre-identified patient populations.

Whether Chinese Data Generalizes

Gerberry pressed on whether data from Chinese studies will replicate globally, including whether adverse events are reported comparably and whether patients enroll partly out of concern about access to medicine.

Barr’s answer defended the data quality directly. Chinese sites are bound by good clinical practice, the government mandates GCP certification, and the national regulator fields considerably more inspectors than the FDA does in the United States. The quality of the data is good.

The limitations he identified are population rather than conduct. These are Chinese patients, predominantly of Han Chinese background, within a relatively standardized medical system. The global setting is noisier, with different cultures and different background therapies before and after treatment.

His practical conclusion: seeing data in China has consistently been strongly indicative of what follows in the United States, and roughly 15 percent of the patient population in a global trial comes from China in any event.

Combination Strategy

Asked how the team prioritizes combinations and moves toward first-line and adjuvant settings, Barr said it depends on unmet medical need, focusing where standard of care is not good or can be improved.

He used Keytruda’s development as the reference. It was developed as immunotherapy plus standard chemotherapy, which succeeded enormously. That leaves two questions: can the immunotherapy be improved, and can the chemotherapy be improved.

Merck wants both. That is the reasoning behind its PD-1 VEGF program, which the company likely will not develop in combination with chemotherapy but rather with a partner agent that is equally active. Pointing to the Chinese data on sacituzumab tirumotecan as evidence of an active drug, his ambition is novelty in every component of the regimen.

The Personalized Cancer Vaccine

The Moderna collaboration is now more than ten years old. The original design logic was to focus on tumors with high tumor mutational burden that respond to immune stimulation, which is why melanoma was chosen, and on early-stage disease rather than late, to work with as intact an immune system and as healthy a patient population as possible.

Phase two data presented over the years showed high efficacy and durability for recurrence-free survival and distant metastasis-free survival.

The question now is whether both high neoantigen load and immune responsiveness are required, or whether immune responsiveness alone suffices. Studies in renal cell cancer, which carries relatively less tumor mutational burden but is highly immune responsive, will test that. Other tumors with differing sensitivity to pembrolizumab but high mutational burden are also being examined.

Barr was candid that he does not know how it all resolves, calling it genuinely new therapy, and urged attendees to look closely at the upcoming ESMO data.

His framing of why the result matters: the algorithm worked. If high mutational burden is not required, the approach opens to tumors long considered immunologically cold. Manufacturing remains demanding, though he expects it to prove easier than CAR-T.

Designing Trials in the Curative Setting

Moving earlier into curative settings pushes endpoints years away, which Gerberry raised as a design problem.

Barr agreed the central question is whether the therapy represents a cure, and noted that cure means several things in cancer care. The time coordinate matters enormously, since it requires waiting to see whether patients remain cancer-free.

His answer is twofold: the patience to wait that long, and correlates of protection to read in the interim. Practically, it means starting long-term studies very early.

A Closing Request

Barr closed with a plug for American cancer centers to enroll more patients in phase three trials, on the grounds that Americans want evidence a drug works in Americans.

Key Takeaways

1. Category does not determine ADC behavior. Antibody, linker and payload differences are profound within a single target class.

2. Chinese sites differ by mindset, not just regulation. Large enrollment and drug-focused inquiry rather than investigator-specific questions.

3. Data quality concerns were addressed directly. GCP certification is mandated and the national regulator fields more inspectors than the FDA.

4. Merck wants to improve both halves of the regimen, pursuing novelty in the immunotherapy and the partner agent.

5. The vaccine result’s significance is that the algorithm worked, which would open immunologically cold tumors if high mutational burden proves unnecessary.

6. Curative-setting trials require patience and correlates. Endpoints years away mean starting long-term studies very early.