Genmab’s Three Positive Phase III Readouts Set Stage for Potential 2027 Cancer Launches

Key Points

• Genmab reported three positive Phase III readouts for EPKINLY in first-line diffuse large B-cell lymphoma, Rina-S in platinum-resistant ovarian cancer, and petosemtamab in first-line head and neck cancer. The results could support multiple product launches beginning in 2027.
• EPKINLY plus R-CHOP reduced the risk of progression or death by 51% in previously untreated DLBCL, while Rina-S reduced that risk by 71% in its primary ovarian cancer analysis and also met its overall-survival endpoint. Genmab plans to file Rina-S for approval as soon as possible.
• Petosemtamab plus pembrolizumab met both primary endpoints in first-line PD-L1-positive recurrent or metastatic head and neck cancer, including a 50% reduction in the risk of death. Genmab estimates the petosemtamab program addresses roughly 315,000 patients and has multibillion-dollar peak-sales potential.

Genmab A/S NASDAQ: GMAB said three positive Phase III readouts across lymphoma, ovarian cancer and head and neck cancer could support multiple potential product launches beginning in 2027, as the company seeks to increase growth from medicines it owns or co-develops.

Chief Executive Officer Jan van de Winkel said the company reported positive late-stage results during the month for EPKINLY in first-line diffuse large B-cell lymphoma, Rina-S in platinum-resistant ovarian cancer, and petosemtamab in first-line head and neck cancer. He said the results have the potential to alter treatment standards in their respective indications, though full datasets have not yet been presented.

EPKINLY Shows Progression-Free Survival Benefit in DLBCL

Chief Medical Officer Tahi Ahmadi said the Phase III EPCORE DLBCL-2 study evaluated EPKINLY plus R-CHOP in previously untreated diffuse large B-cell lymphoma patients with an International Prognostic Index score of 2 to 5. The combination reduced the risk of progression or death by 51% versus R-CHOP, corresponding to a hazard ratio of 0.49 and a p-value below 0.0001, according to the company.

Ahmadi said the regimen used a fixed-duration subcutaneous treatment approach and had safety consistent with the known profiles of epcoritamab, the active ingredient in EPKINLY, and R-CHOP. Genmab and AbbVie plan to engage global health authorities and present the full results at a future medical meeting.

Genmab said EPKINLY’s current approved uses address about 27,000 patients across the U.S., EU5 and Japan. Potential launches in second-line and first-line DLBCL, along with first-line follicular lymphoma, could expand the addressable population to roughly 146,000 patients, including about 70,000 first-line DLBCL patients.

The company maintained its view that EPKINLY has peak sales potential above $3 billion and said it believes it is approximately one to 1.5 years ahead of competitors in the frontline DLBCL setting.

Rina-S Data Support Broad Ovarian Cancer Development

Genmab also reported that its wholly owned Rina-S treatment met the primary progression-free survival endpoint in the Phase III RAINFOL-02 trial in platinum-resistant ovarian cancer. In the intent-to-treat population, Rina-S reduced the risk of progression or death by 71%, with a hazard ratio of 0.29, the company said.

In the primary analysis population, where patients with folate receptor alpha expression above 75% PS2 positivity were required to have been treated with mirvetuximab, Rina-S reduced the risk of progression or death by 67%, with a hazard ratio of 0.33. The trial also met its key secondary overall-survival endpoint in both analyzed populations, according to Genmab.

Ahmadi said safety was consistent with prior results and that no new safety signals were identified. He said the company believes the treatment’s efficacy across folate receptor alpha expression levels and among patients previously treated with mirvetuximab could enable use in a broader patient population. Genmab plans to file “as soon as possible,” targeting a potential 2027 launch.

Separately, Phase II RAINFOL-01 data in heavily pretreated patients showed a confirmed response rate of 45.9% and median duration of response of 12.1 months, Genmab said. The company cited no ocular events, neuropathy or interstitial lung disease signal in that dataset, while 1.8% of patients discontinued because of treatment-related adverse events.

Genmab said six Phase III Rina-S trials have been announced or initiated across ovarian and endometrial cancers, targeting an estimated 79,000 patients. The company continues to see peak sales potential above $2 billion for the program.

Petosemtamab Meets Dual Primary Endpoints in Head and Neck Cancer

Petosemtamab plus pembrolizumab met both dual primary endpoints in the Phase III LiGeR-HN1 study in first-line PD-L1-positive recurrent or metastatic head and neck cancer, Genmab said. The study enrolled approximately 700 patients and compared the combination with pembrolizumab alone.

At the first interim analysis, the combination produced a statistically significant and clinically meaningful improvement in response rate regardless of HPV status, according to the company. It also reduced the risk of death by 50% and was generally well tolerated, with no new safety signals reported.

Ahmadi said updated Phase II data presented at ESMO showed a 63% confirmed response rate and median overall survival of 28.2 months in first-line head and neck cancer. He added that the pembrolizumab control arm in the Phase III study performed in line with historical experience, though Genmab deferred detailed subgroup and control-arm data until a future medical conference.

The company is also advancing petosemtamab in colorectal cancer. At ESMO, Genmab reported response rates of 81% in left-sided first-line colorectal tumors and 67% in second-line disease for petosemtamab plus chemotherapy, with disease-control rates above 90% in both settings. Two Phase III colorectal cancer studies are underway, while LiGeR-HN2 in previously treated head and neck cancer is expected to read out in the first quarter of 2027.

Genmab said petosemtamab’s development program addresses approximately 315,000 patients and represents a multibillion-dollar peak-sales opportunity. Chief Financial Officer Anthony Pagano said the company continues to stand behind its previously communicated peak-sales estimates and financial commitments, while declining to provide updated expense guidance during its quiet period ahead of third-quarter results.

About Genmab A/S (NASDAQ:GMAB)

Genmab A/S is a biotechnology company headquartered in Copenhagen, Denmark, focused on discovering and developing differentiated antibody-based medicines for the treatment of cancer and other serious diseases. The company uses proprietary antibody technologies, including DuoBody and HexaBody, to create therapies designed to engage the immune system or target specific disease-related proteins.

Genmab's marketed and partnered products include DARZALEX (daratumumab) for multiple myeloma, developed with Johnson & Johnson; EPKINLY (epcoritamab) for certain types of B-cell lymphoma, developed with AbbVie; and Tivdak (tisotumab vedotin) for cervical cancer, developed with Seagen.

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