Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer

Titre officiel

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer

Sommaire:

L’étude vise à évaluer l’innocuité, la pharmacocinétique et l’efficacité préliminaire de JNJ-61186372 en monothérapie et en association avec le lazertinib, et à déterminer la dose recommandée pour la phase II (RP2D) [monothérapie], la dose recommandée dans la combinaison pour la phase II (RP2CD) [polythérapie], et à déterminer la dose recommandée pour la phase II (RP2q3W) avec la chimiothérapie d’association (JNJ-61186372 en association avec le traitement standard de carboplatine et pemetrexed) dans un cycle de traitement de 21 jours pour les participants atteints d’un cancer du poumon non à petites cellules (CPNPC) avancé.

Description de l'essai

Primary Outcome:

• Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
• Part 2: Number of Participants With Adverse Events (AEs) and Serious AEs
• Part 2: Overall Response Rate (ORR)
• Part 2: Duration of Response (DOR)
• Part 2: Percentage of Participants With Clinical Benefit
• Trough Serum Concentration (Ctrough) of Amivantamab
• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab

Secondary Outcome:

• Maximum Serum Concentration (Cmax) of Amivantamab
• Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab
• Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of Amivantamab
• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab
• Trough Serum Concentration (Ctrough) of Amivantamab
• Maximum Serum Concentration (Cmax) of Lzertinib
• Time to Reach Maximum Observed Serum Concentration (Tmax) of Lazertinib
• Trough Serum Concentration (Ctrough) of Lazertinib
• Accumulation ratio (R) of Amivantamab
• Number of Participants With Anti-Drug Antibodies (ADA)
• Progression-Free Survival (PFS)
• Time to Treatment Failure (TTF)
• Overall Survival (OS)

This open label (all participants know the identity of the study drug), multicentre (more than one study site), first-in-human study consists of 2 parts. Part 1 is a Amivantamab Monotherapy and Combination Dose Escalations and Part 2 Amivantamab Monotherapy and Combination Dose Expansions. In Part 1, participants with evaluable NSCLC will be enrolled into cohorts at increasing dose levels of Amivantamab monotherapy, the RP2CD of the Amivantamab and lazertinib combination which will be administered in 28 day treatment cycles, and RP2q3W of Amivantamab in combination with standard of care carboplatin and pemetrexed (chemotherapy combination) which will be administered in 21 day treatment cycles. The dose will be escalated until the maximum tolerated dose (MTD, or maximum administered dose [MAD], if no MTD is found) is reached. Part 1 will follow a traditional 3+3 design. At each dose level, 3 participants will complete Cycle 1. If no dose limiting toxicity (DLT) occurs in these 3 participants, then escalation will continue in a new cohort of 3 participants. Data from Part 1 will be used to determine one or more RP2D regimen(s). In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed after previous treatment will be enrolled and receive Amivantamab at the RP2D determined in Part 1 as a monotherapy at the RP2D regimen(s), or in combination with lazertinib at the RP2CD regimen. For both parts, the study consists of following periods: an optional pre-Screening period; a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until 30(+7) days after the last dose of study drug or prior to starting any subsequent anti-cancer treatment, whichever comes first); and a Follow Up period (approximately 6 months). All participants will be followed for survival in the post-treatment follow-up period until the end of study and safety will be monitored throughout the study.

Voir cet essai sur ClinicalTrials.gov