Lieu CH, et al. – Experts aspired to analyze safety, tolerability, and pharmacokinetics of cobimetinib and duligotuzumab in patients with previously treated locally advanced or metastatic cancers with mutant KRAS. As per observations, tolerability and efficacy of this combination were limited. In view of this outcome, the study did not proceed to expansion stage and closed for enrollment.

Methods

• For this phase Ib dose-escalation study with a planned expansion phase, patients with KRAS-mutant solid tumors were eligible.
• At 1,100 mg every 2 weeks (q2w), duligotuzumab was given intravenously (IV).
• On the other hand, cobimetinib was given orally in a standard 3+3 design to identify the recommended phase II dose (RP2D).
• Moreover, the primary objective was to evaluate the safety and tolerability of this combination.

Results

• This study incorporated twenty-three patients.
• Grade 4 hypokalemia and grade 3 mucosal inflammation, asthenia, and dermatitis acneiform were dose-limiting toxicities (DLTs).
• Results revealed grade 3 or worse adverse events (Aes) in seventy percent of patients.
• At least, 1 dose of duligotuzumab and cobimetinib had been missed by five (22%) and 12 (52%) patients.
• Moreover, 9 (39%) patients required a cobimetinib dose reduction.
• Because of AE, three (13%) patients discontinued.
• In addition, best response was limited to 9 patients with stable disease and 13 patients with progressive disease.