Genmab Halts Cancer Drug to Bet Big on Late-Stage Winners

COPENHAGEN, Denmark – December 29, 2025

Danish biotechnology giant Genmab announced today it is discontinuing all clinical development for its investigational cancer therapy, acasunlimab. The move, described as a strategic portfolio prioritization, halts a drug that had recently entered Phase 3 trials for non-small cell lung cancer and had shown what the company called an "encouraging" clinical profile.

The decision redirects substantial resources toward what Genmab identifies as its highest-impact late-stage programs: the already-approved EPKINLY® (epcoritamab), petosemtamab, and the antibody-drug conjugate rinatabart sesutecan (Rina-S®). The pivot underscores the brutal realities of modern drug development, where even promising candidates can be cut in the face of intense competition and the high cost of late-stage trials.

“After careful consideration, we have decided to discontinue the acasunlimab program,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab, in a company statement. “Although the data have been encouraging, the compelling opportunities we see in our late‑stage pipeline led us to focus our investments where we believe we can deliver the greatest benefit for patients and shareholders.”

A Promising Candidate with Hidden Risks

Acasunlimab, also known as GEN1046, was a novel bispecific antibody designed to simultaneously block the PD-L1 pathway—a well-known target for cancer immunotherapy—while activating a powerful immune co-stimulatory receptor called 4-1BB. This dual mechanism aimed to deliver a potent, targeted anti-tumor attack, a next-generation approach to immunotherapy.

The drug's primary focus was non-small cell lung cancer (NSCLC), specifically for patients whose disease had progressed after standard immunotherapy and chemotherapy. This is a patient population with a significant unmet need. Just last month, in November 2024, Genmab initiated a global Phase 3 trial, "ABBIL1TY NSCLC-06," to test acasunlimab in this setting. The candidate was also being explored in Phase 2 trials for advanced melanoma and in earlier studies for a range of other solid tumors.

The "encouraging" data mentioned by Genmab likely refers to results from a Phase 2 study presented in mid-2024. In that trial, acasunlimab combined with pembrolizumab (KEYTRUDA®) demonstrated a median overall survival of 17.5 months and a 12-month survival rate of 69% in its target NSCLC population. On the surface, these figures appeared promising.

However, a deeper look at the data revealed potential vulnerabilities. Some analysts had previously noted a concerning trend where the overall survival curve appeared to deteriorate with longer patient follow-up. Furthermore, safety signals raised questions about the drug's long-term viability. Reports indicated an 18% incidence of liver-related adverse events and a high discontinuation rate of 25% in the most effective dosing arm, suggesting that the therapy's toxicity might outweigh its benefits for a significant portion of patients. These underlying risks, combined with the immense cost of running a Phase 3 program, likely factored heavily into Genmab’s calculus. The decision was also preceded by the 2024 opt-out of Genmab's original development partner, BioNTech, which chose not to proceed with the asset based on its own portfolio strategy, leaving Genmab to carry the program forward alone.

The Competitive Gauntlet of Oncology

Genmab's decision was explicitly linked to "the evolving competitive landscape." The field of oncology, and particularly NSCLC, is one of the most crowded and fiercely competitive areas in pharmaceuticals. Dozens of companies, from global pharma giants to nimble biotechs, are vying to develop the next standard of care.

For a new drug to succeed in the post-PD-1/PD-L1 inhibitor setting, it must demonstrate not just efficacy, but a clear and substantial improvement over existing or emerging competitors. This includes a superior safety profile, a significant survival benefit, or a novel mechanism that can overcome treatment resistance.

With mixed signals on its long-term efficacy and notable safety concerns, acasunlimab faced a difficult path to becoming a best-in-class or even a competitive agent. The strategic decision to terminate the program reflects a disciplined assessment that the resources required to prove its value—hundreds of millions of dollars for Phase 3 trials and commercial launch preparations—could be better deployed elsewhere. This type of pipeline pruning, while difficult, is a hallmark of mature biotechnology companies focused on maximizing their return on research and development investment.

Doubling Down on a Trio of High-Potential Assets

By stepping away from acasunlimab, Genmab is sharpening its focus and concentrating its financial firepower on three key late-stage programs it believes have a clearer path to success and greater market potential.

First is EPKINLY® (epcoritamab), a bispecific antibody co-developed with AbbVie. Already approved for certain types of large B-cell lymphoma, EPKINLY is a commercial-stage asset with proven success, and its development continues in other blood cancers and solid tumors. Its established profile makes it a more predictable and powerful growth driver for the company.

Next is petosemtamab, another of Genmab’s wholly-owned bispecific antibodies. It is in late-stage development for head and neck cancer and has shown promising data, positioning it as a potential cornerstone of the company's future oncology portfolio.

Finally, there is rinatabart sesutecan (Rina-S®), an antibody-drug conjugate (ADC) being developed for ovarian cancer and other solid tumors. ADCs are a highly promising class of "smart bomb" cancer drugs that deliver potent chemotherapy directly to tumor cells, and Rina-S represents Genmab's significant investment in this cutting-edge technology.

By prioritizing these three diverse but advanced assets, Genmab is betting on programs with either established market validation, strong late-stage data in areas of high need, or leadership in a next-generation therapeutic class. This move is designed to accelerate their development and maximize their chances of reaching patients and achieving commercial success.

A Sign of Strategic Maturity

While the termination of a Phase 3 drug can often spook investors, Genmab was quick to state that the decision does not impact its full-year 2025 financial guidance. This message is intended to signal that the move is a proactive, strategic reallocation rather than a reaction to a sudden financial crisis or catastrophic trial failure. For a company that has been transforming science into medicine for over 25 years, this decision is being framed as a sign of strategic maturity.

“We are highly energized by the momentum of EPKINLY, petosemtamab and Rina‑S, and we remain committed to executing these programs with speed and rigor,” van de Winkel added, reinforcing the company's forward-looking focus.

The pivot away from acasunlimab, a drug with a complex risk-reward profile, in favor of a trio of more clearly defined late-stage assets, illustrates the disciplined approach required to thrive in the high-stakes world of biotechnology. It highlights a company making tough choices to streamline its pipeline, manage risk, and concentrate its efforts on therapies it believes are most likely to become transformative medicines for patients and create significant value for the company and its shareholders in the years to come.