Genmab may have arrived in Spain with updated data from a pair of phase 2 studies from the main prize of its Merus buyout, but the company had bigger news to share.
On Friday evening of the European Society for Medical Oncology (ESMO) conference, Genmab quietly published a press release revealing that rinatabart sesutecan (Rina-S) had aced its first phase 3 test.
Genmab had been evaluating the FRα-directed antibody-drug conjugate (ADC) in the trial of 582 patients with platinum-resistant ovarian cancer (PROC) regardless of FRα expression level or prior treatment with AbbVie’s Elahere.
The study hit its primary endpoint of progression-free survival (PFS), with Rina-S demonstrating a statistically significant and clinically meaningful 71% reduction in the risk of disease progression or death in all patients with PROC, regardless of FRα expression, when compared to investigator’s choice chemotherapy, Genmab explained in the October 23 release.
Among the 492 patients with FRα expression above 75% at PS2+, Rina-S demonstrated a 67% reduction in the risk of disease progression or death, according to Genmab.
The trial also hit its secondary endpoint of demonstrating an overall survival (OS) hazard ratio of 0.43 in the overall population and 0.44 in the high-FRα population. No new safety signals or unexpected safety concerns identified, Genmab noted.
The Friday readout is the first of a range of phase 3 studies for Rina-S in various ovarian cancer settings, as well as earlier-stage studies in non-small cell lung cancer and gastrointestinal cancers.
Responding to the readout, William Blair analysts noted that while only high-level data has been disclosed so far, “the PFS and OS results achieved with Rina-S appear to be highly competitive with Elahere and suggest efficacy across a broader patient population.”
Details in the press release are limited with only high-level data disclosed, but based on the topline results, the PFS and OS results achieved with Rina-S appear to be highly competitive with Elahere and suggest efficacy across a broader patient population.”
Genmab CEO Jan van de Winkel, Ph.D., said the phase 3 win “mark[s] a significant milestone for Genmab and strengthen our confidence in Rina-S’s potential for patients with platinum-resistant ovarian cancer.”
“We look forward to discussing these results and potential next steps with regulatory authorities worldwide,” the CEO added.
AbbVie has been defending its business in the courts. Last year, the U.S. Big Pharma accused Genmab of being “willfully blind” to the theft of trade secrets when buying Rina-S in its $1.8 billion ProfoundBio takeover. Genmab provided (PDF) an update on the allegations, which it refutes, in its second-quarter earnings.
Digging into the petosemtamab data
While the late-stage data for Rina-S are evidence of the wisdom of Genmab’s Profound Bio buyout, the Danish biopharma used the ESMO conference to back up the rationale for its $8 billion acquisition of Merus a year ago.
Acquiring the Netherlands-based biotech brought on board the late-stage bispecific antibody petosemtamab that works by binding EGFR and LGR5 on cancer cells. EGFR is a long established cancer drug target, while LGR5 is new.
By hitting both receptors, Merus had been hoping that the bispecific can inhibit EGFR signaling, drive EGFR degradation via LGR5 and engage the immune system. Before the biotech was picked up by Genmab, Merus had been assessing petosemtamab plus chemotherapy in patients with metastatic colorectal cancer (mCRC).
Genmab disclosed some updated data from this trial at ESMO, which tied petosemtamab to an 82% overall response rate (ORR) among the 17 patients who received this regimen in the first-line setting, and a 70% ORR in patients in the second-line setting.
Responding to an abstract of the data ahead of the conference, William Blair analysts said the readout “reinforce[s] our view that CRC represents significant upside to peto’s value, which is primarily based on the head and neck squamous cell carcinoma.”
The company also disclosed fresh data from a study looking at petosemtamab in the head and neck setting, a typically difficult to treat type of cancer. A total of 45 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) received petosemtamab and Merck & Co.’s megablockbuster Keytruda. Among the 43 evaluable patients, the ORR was 63%, with median PFS of nine months.
The most common treatment-emergent event was asthenia—a general feeling of physical or mental weakness—which affected just over half (51%) of patients, a skin condition called acneiform, which affected 49%, and rash, which affected 44% of participants.
Amaury Daste, M.D., an investigator on the study, described the data as “very interesting” with a “similar or higher objective response rates” than he’d expect to see with patients receiving chemotherapy and Keytruda alone.
It’s important for physicians to be on the lookout for infusion reactions from the drug, although these can be managed by starting patients on a very low dose of the drug, Daste explained in an interview on the sidelines of the conference to Fierce.
“In my unit, we are very careful,” explained Daste, who is a medical oncologist at Hospital Center University De Bordeaux in France. “We prepare [a] corticosteroid in case of reactions. So it’s manageable.”
The biggest benefit of the drug is that it offers similar efficacy to standard of care, while being “much more tolerated than chemotherapy,” he said.
HNSCC is regarded as a key opportunity for petosemtamab, with William Blair analysts modelling $4 billion in peak sales for this indication alone.
A phase 3 readout for petosemtamab in first-line HNSCC is expected this quarter, according to the analysts, with phase 3 results in second- and third-line HNSCC expected in the first quarter of 2027.