Adagene has signed a clinical trial collaboration and supply agreement with Merck (MSD) to assess its drug candidates, ADG116 and ADG126, in combination with the latter’s Keytruda (pembrolizumab) for the treatment of solid tumours.
ADG116 and ADG126 are monoclonal antibodies that target CTLA-4 while Keytruda is an anti-programmed cell death protein 1 (anti-PD-1) drug.
The deal covers two open-label, dose-escalation and expansion Phase I clinical trials of the combination treatments in advanced or metastatic solid tumour patients.
One trial, named ADG 116-P001, will test the safety, tolerability and recommended Phase II dose of ADG116 plus Keytruda at multiple centres across Asia and the US. Adagene planned for dose escalation of up to 10mg/kg during the trial.
The trial is based on favourable pharmacodynamic (PD) markers and pharmacokinetic (PK) profile data, early results from the ADG116-1003 trial, preclinical and safety tolerability data and positive outcomes from meetings with Safety Review Committee.
Results from ADG116-1003 showed that ADG116 was well tolerated in 17 patients, without dose-limiting toxicities, unpredicted safety signals or drug-linked grade 2, grade 3 or grade 4 toxicities.
The second trial under the latest agreement will evaluate ADG126 plus Keytruda in Asia and the US.
Referred to as ADG 126-P001, this trial is based on favourable preclinical data, where ADG126 was well tolerated at doses up to 200mg/kg.
The drug candidate also had an encouraging dose-dependent antitumor response in several immune-competent mouse tumour models as a monotherapy and combination with anti-PD-1 and various other drugs.
Adagene interim chief medical officer Steven Fischkoff said: “ADG116 programme is at the 3mg/kg dose level now which is where the commercial CTLA-4 therapy had been approved previously in mono and combination for specific indications.
“We expect to see differentiation going forward of our programmes.”
Last week, Merck reported that the Phase III KEYNOTE-522 trial of Keytruda plus chemotherapy showed a statistically significant event-free survival in high-risk early-stage triple-negative breast cancer patients.