A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumours Harboring an NRG1 Fusion

Titre officiel

A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumours

Sommaire:

Il s’agit d’une étude d’augmentation de la dose de phase I/II, ouverte, multicentrique, multinationale, et à agent unique, visant à évaluer l’innocuité, la tolérabilité, la pharmacocinétique, la pharmacodynamique, l’immunogénicité et l’activité antitumorale du zénocutuzumab (MCLA-128) chez des patients présentant des tumeurs solides porteuses d’une fusion du gène NRG1.

Description de l'essai

Primary Outcome:

• Characterize the safety and tolerability of zenocutuzumab (MCLA-128)
• Objective overall response rate (ORR)
• Duration of response (DOR)
• Correlation of anti-tumour activity and biomarkers
• Correlation of anti-tumour activity and biomarkers
• Correlation of anti-tumour activity and biomarkers
• Correlation of anti-tumour activity and biomarkers

Secondary Outcome:

• Incidence of AE [safety and tolerability]
• Maximum plasma concentration [Cmax]
• Volume of distribution [V]
• Volume of distribution at steady state [Vss]
• half-life [t1/2]
• Area under the concentration versus time curve from time zero to time t [AUC0-t]
• area under the concentration versus time curve [AUC0-∞]
• time to reach maximum concentration [tmax]
• Incidence of anti-drug antibodies against zenocutuzumab (MCLA-128)
• serum titers of anti-drug antibodies
• Anti-tumour response of zenocutuzumab (MCLA-128) by RECIST v1.1
• Clinical Benefit Rate (CBR) of zenocutuzumab (MCLA-128)
• Progression Free Survival (PFS) and survival

Study Design : This open label (all participants know the identity of the study drug), multicentre (more than one study site), first-in-human study consisting of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed. Part 2 new patient populations examined:

• Group F: Patients with NSCLC with documented NRG1 fusion

• Group G: Patients with pancreatic cancer with documented NRG1 fusion

• Group H: Patients with any other solid tumour with documented NRG1 fusion For these new patient populations, Part 2 will further characterize the safety and tolerability of the selected dose level of zenocutuzumab (MCLA-128), as well as assessment of CBR, defined as the proportion of patients with a CR, PR or durable SD (SD for at least 12 weeks in duration). For the new patient populations, overall response rate (ORR) and duration of response (DOR) will be described. The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period (treatment cycles of 28 days); and Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 2 years). Participants' safety will be monitored throughout the study. Number of Sites: Up to 40 sites are estimated to be involved during Parts 1 and 2 of the study. Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.

Voir cet essai sur ClinicalTrials.gov