Merus has found favourable safety profile and early signs of anti-tumour activity in patients with advanced solid tumours during the ongoing phase 1/2 clinical trial of the bispecific antibody productcandidate, MCLA-128.
MCLA-128 is a novel full-length Immunoglobulin G (IgG) bispecific antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC), which is designed to bind to human epidermal growth factor receptors, HER2 and HER3, present on several solid tumour cells.
Merus expects to present interim clinical data for MCLA-128 from a first-in-human Phase 1/2 clinical trial at the American Association for Cancer Research (AACR) 2016 annual meeting currently being held in New Orleans, US.
The company will present on the open-label dose escalation phase (part 1) of the Phase 1/2 clinical trial.
The primary objectives in part 1 of the clinical trial are to determine a maximum tolerated dose and to establish the recommended dose for a phase 2 clinical trial of MCLA-128; the secondary objectives include assessing its safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumour activity.
Merus chief medical officer Setareh Shamsili said: "We believe the interim data we are presenting from part one of this first clinical trial of MCLA-128 demonstrates a favourable safety profile and early signs of anti-tumour activity.
"In part two of this clinical trial, we will continue to evaluate MCLA-128 for safety and efficacy in patients with selected tumour types and patients with HER2 amplification in other tumour types.
"We expect to report top-line data from both parts of this trial in the first half of 2017."
In part one, known as the dose escalation phase of MCLA-128’s Phase 1/2 clinical trial, patients with advanced solid tumours that are relapsed or refractory to at least one prior regiment of available standard treatment or for whom no curative therapy is available were enrolled.
MCLA-128 was administered every three weeks (q3w) as an intravenous infusion over 60-120 minutes and toxicities were assessed at escalating dose levels.
In all, 28 patients received MCLA-128 in nine dose escalation cohorts, in a range of 40mg to 900mg flat dose.
However, a maximum tolerated dose was not reached at the dose level of 900mg.
The cumulative safety and available PK data, along with the aid of a PK simulation study, were used to support a recommended dose for a Phase 2 clinical trial of 750mg q3w, administered over 120 minutes and encouraging signs of anti-tumour activity were observed.
Three patients remain in the trial to date, with one metastatic non-small cell lung cancer patient who is experiencing an ongoing partial response after more than nine months, one metastatic gastroesophageal junction cancer patient with stable disease after over five months, and one metastatic colorectal cancer patient with stable disease after over six months.
In addition, one metastatic breast cancer patient with stable disease received five months of MCLA-128 treatment before disease progression.
MCLA-128 was well-tolerated with a favourable safety profile in patients with advanced tumours treated at doses up to 900mg q3w.
The expansion phase, part two, of the clinical trial is ongoing at the recommended Phase 2 dose of 750mg q3w, enrolling patients with selected tumour types with HER2 amplification.