ESMO26: Evidence for GSK's mo-rez builds in ovarian cancer

New data from GSK's BEHOLD-1 study of B7-H4-targeted antibody-drug conjugate mocertatug rezetecan (mo-rez) reinforce earlier results for a key candidate in the company’s oncology pipeline.

At last count, the ADC was associated with an objective response rate (ORR) of 62% in the phase 1b trial involving patients with platinum-resistant ovarian cancer (PROC), in line with an earlier readout reported in April, at the dose selected for a phase 3 programme (5.8 mg/kg).

Meanwhile, the durability of the benefit was backed up by a 12.2-month median duration of response and median progression-free survival of 11.1 months, while safety results were consistent with previous studies.

Severe (Grade 3 or higher) treatment-related adverse events (TRAE) were quite frequent, observed in 71% of patients, but only 2% discontinued therapy because of side effects and the same proportion developed interstitial lung disease or pneumonitis, recognised side effects of some ADCs.

"Despite advances in ovarian cancer, platinum-resistant disease is one of the hardest to treat, and many patients still experience limited benefit from available treatment options," commented BEHOLD-1 study investigator Vanda Salutari of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome, Italy.

"The duration of response and progression-free survival observed in BEHOLD-1 are particularly encouraging relative to what is typically seen in this setting where prolonged disease control remains difficult to achieve," she added.

Mo-rez is one of two ADCs that GSK has licensed from Chinese biopharma company Hansoh alongside B7-H3-targeted risvutatug rezetecan (ris-rez), in a pair of deals that could be worth up to $3.28 billion, including upfront fees of $270 million. Results from the phase 1b EMBOLD PanTumour-101 of ris-rez in small cell lung cancer (SCLC) are due to be presented later at ESMO.

Hesham Abdullah, GSK's global head of oncology, said the company is accelerating the development of mo-rez on the back of the encouraging results, with five pivotal trials now ongoing "across gynaecological cancers."

Those include BEHOLD-Ovarian01 and BEHOLD-Ovarian02 in platinum-sensitive ovarian cancer, and BEHOLD-Ovarian03 looking at mo-rez in the first-line maintenance setting for ovarian cancer without homologous recombination deficiency.

GSK is also developing the drug as a second-line treatment for advanced and recurrent endometrial cancer in BEHOLD-Endometrial01, and first-line maintenance for mismatch repair proficient endometrial cancer in BEHOLD-Endometrial02.