GSK’s cancer R&D chief has suggested the latest slice of early-stage data on its B7-H4-directed antibody-drug conjugate (ADC) has “reinforce[d] our belief in the asset,” as the therapy races through a clutch of phase 3 studies.
The British Big Pharma has been evaluating various doses of mocertatug rezetecan (mo-rez) in the ongoing Behold-1 trial in patients with platinum-resistant ovarian cancer (PROC) or advanced/recurrent endometrial cancer. Fresh data unveiled at the European Society for Medical Oncology conference in Madrid covered 45 PROC patients at around a 13-month follow-up who received the selected dose for the phase 3 studies of 5.8 mg/kg.
Among these patients, mo-rez achieved a confirmed objective response rate (cORR) of 62%, with a median duration of response (DoR) of 12.2 months and median progression-free survival (PFS) of 11.1 months.
The ORR matches an earlier readout from the study back in April. GSK's global head of oncology R&D, Hesham Abdullah, M.D., told journalists on a call that the additional data on DoR and PFS is “quite encouraging for this patient population.”
These patients “typically tend to have shorter duration of response,” with PFS “in the six-to-eight-month timeframe,” Abdullah pointed out.
A total of 71% of the patients experienced a treatment-related adverse event (TRAE) at graded 3 or higher, most of which were hematologic, according to GSK. One of the 45 patients receiving the phase 3 dose discontinued treatment due to a TRAE, while there was one case of interstitial lung disease.
When asked by Fierce whether GSK was concerned by the rate of TRAEs, Abdullah pointed out that the safety profile of mo-rez is driven by the ADC’s topoisomerase I inhibitor payload. As a result, the “majority” of TRAEs will be related to heme toxicity or myelosuppression, he suggested.
Unlike phase 1 studies of some of mo-rez’s competitors, this trial’s investigators had been allowed to decide whether to provide growth factors or other prophylactic medications to manage some of these side effects, according to Abdullah. But this will be amended for the later studies.
“In the phase 3 program, we’ve actually changed that and made it much more prescriptive,” he told Fierce. “So my anticipation is you'll probably see that [TRAE profile] will be quite different in the late-stage studies.”
B7-H4 is an immune checkpoint that is widely expressed in gynecological cancers and is low in normal tissues. GSK is already running five phase 3 studies of mo-rez, consisting of three in ovarian cancer of varying resistance to treatment, as well as a pair of studies in endometrial cancer.
“We actually took this program in about maybe 18 months from phase 1b to phase 3,” Abdullah explained to journalists. “That's just one example of what we've done with acceleration and execution, and continuing to generate data from our own global development program for the asset.”
Mo-rez is one of two ADCs that GSK licensed from Hansoh Pharma. The other ADC, B7-H3-directed ris-rez, proved its worth in a phase 3 study in China last month for patients with small cell lung cancer. That readout raised expectations that ris-rez could ultimately prove a threat to the likes of Amgen and Merck & Co. in the lung cancer field.
This month, GSK unveiled the first global data for ris-rez, which demonstrated a 61% overall response rate in its own phase 1b trial. Hansoh has arrived at ESMO with more phase 3 data from a Chinese trial of ris-rez, which the company will present on Monday.
GSK isn’t the only Big Pharma that has turned to Hansoh to fuel its ADC ambitions. This month also saw Roche expand its own relationship with the Chinese drug developer by penning a mammoth $15 billion biobucks pact spanning a “broad portfolio of ADC programs.”
When asked by Fierce whether GSK would consider heading back to Hansoh to stock up on fresh ADC tech, Abdullah pointed out that last year the British Big Pharma penned a 12-drug deal with another Chinese R&D powerhouse, Hengrui Pharma.
“So we already have kind of a broader collaboration with another large biopharma company in Hengrui, and that actually spans across a number of different modalities that may include ADCs, may include small molecules, may include immune cell engagers,” he said.
“I can't necessarily disclose which targets or modalities, but I can tell you that … at least for oncology, we have actually up to about maybe six or seven targets that are part of that collaboration,” Abdullah continued.
“I’m not saying that we wouldn't necessarily go back and look for additional opportunities to collaborate with different partners,” he added. “That's always something that's on our mind.”
ESMO was only one stopover in an eventful period for Abdullah and his oncology team. The meet-up came just days after GSK’s immunotherapy Jemperli earned a first-in-class FDA approval in a specific type of rectal cancer, and ahead of an imminently expected green light from the regulator for the ALK inhibitor neladalkib, which was acquired in the summer’s $10.6 billion buyout of Nuvalent.