Genmab’s acquisition spree starts to pay off with new ovarian and colorectal cancer data

Why it matters: The results provide the first randomized Phase 3 evidence for Rina-S, the lead asset in Genmab’s $1.8 billion (€1.7 billion at the time) acquisition of ProfoundBio in 2024. They also suggest that a drug targeting folate receptor alpha (FRα) could benefit a broader population than the one eligible for AbbVie’s approved FRα-targeting treatment, Elahere.

• Ovarian cancer accounted for an estimated 70,300 new cases and 44,800 deaths in Europe in 2024. Around 70–90% of women with advanced disease experience a recurrence after initial treatment.
• Patients whose cancer returns or grows within six months of platinum chemotherapy have limited options. “Platinum-resistant ovarian cancer remains one of the greatest challenges in gynecologic oncology,” said Angeles Alvarez Secord, the trial’s lead investigator at Duke Cancer Institute, in a press release. “The 71% reduction in the risk of disease progression and 57% reduction in the risk of death underscore the potential of Rina-S to change clinical practice if approved by offering a therapeutic option for a broad patient population.”

By the numbers: The randomized RAINFOL-02 trial compared Rina-S, which delivers the chemotherapy drug exatecan to FRα-expressing cells, against four conventional chemotherapies: paclitaxel, topotecan, pegylated liposomal doxorubicin or gemcitabine.

• In all 584 patients, Rina-S reduced the hazard of progression or death by 71% (HR 0.29) and the hazard of death by 57% (HR 0.43).
• In a predefined 492-patient primary analysis excluding patients with high FRα expression who had not previously received Elahere where available, the corresponding reductions were 67% (HR 0.33) and 56% (HR 0.44). All four results were statistically significant.

Backstory: The outcome follows Phase 2 data presented earlier this month, showing a 45.9% confirmed response rate among 109 patients, median progression-free survival of 9.5 months and median response duration of 12.1 months. About one-third had previously received Elahere.

As European Biotechnology reported, Genmab has discontinued or deprioritized several other ADC programmes acquired from ProfoundBio. That left Rina-S carrying much of the burden of justifying the takeover.

Reality check: Genmab has disclosed the relative survival benefit but not median survival times, detailed Phase 3 safety results or outcomes by FRα expression level. The open-label trial also relied on investigator-assessed progression-free survival; results from blinded independent review have not been released.

• In Phase 1/2, anemia and neutropenia, a shortage of infection-fighting white blood cells, each affected 57.8% of patients. Serious adverse events occurred in about one-third, although only 5.5% discontinued treatment because of adverse events.

• Rina-S was tested against conventional chemotherapy, not Elahere or newer options, including Keytruda plus paclitaxel, approved in the EU for certain PD-L1-positive patients, and relacorilant plus nab-paclitaxel, which received a positive EMA opinion in September.
• Competition among FRα-targeting ADCs is growing. AstraZeneca’s Phase 3 trial compares AZD5335 against Elahere in high-FRα tumors and chemotherapy in low-FRα tumors. Canada’s Zymeworks reported at ESMO a 55% response rate with ZW191 in evaluable high-grade serous ovarian cancer patients with low or negative FRα expression, versus 69.2% in those with high expression. These early response rates cannot be directly compared with Genmab’s randomized survival results.

Elsewhere in Genmab’s pipeline: The company also reported fresh Phase 2 results for petosemtamab, the EGFR/LGR5-targeting bispecific antibody acquired through its $8 billion (€7 billion) takeover of Dutch biotech Merus in 2025.

• Petosemtamab plus chemotherapy produced confirmed and unconfirmed response rates of 75% and 67% among evaluable first- and second-line metastatic colorectal cancer patients, respectively. The updated single-arm analysis included 79 treated patients, with median follow-up of 5.9 and 7.1 months.
• On 24 October, Genmab and Incyte announced a collaboration to test petosemtamab with Incyte’s KRAS G12D inhibitor and chemotherapy, potentially extending the programme beyond the RAS/BRAF wild-type population studied so far.

What’s next: Genmab plans to discuss Rina-S with regulators and present detailed data at a future medical meeting. It hosts an investor update on 28 October and lists four additional Phase 3 studies in ovarian and endometrial cancer.

Bottom line: Genmab’s two major oncology acquisitions are beginning to deliver: ProfoundBio’s Rina-S has demonstrated a survival benefit in Phase 3, while Merus’s petosemtamab has shown promising early activity in colorectal cancer. The former still needs detailed survival and safety data; the latter must prove itself in randomized trials.