A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer

Titre officiel

A Phase 1b/2, Open-Label Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer

Sommaire:

The purpose of this study is to assess the anti-tumour activity of amivantamab as a monotherapy (Cohorts A, B, and C), to characterize the safety of amivantamab when added to standard-of care (SoC) chemotherapy in participants with metastatic colorectal cancer (mCRC) (Ph2 cohorts), and to assess the recommended phase 2 combination dose (RP2CD) of amivantamab when added to SoC chemotherapy (Ph1b cohorts).

Description de l'essai

Primary Outcome:

• Cohorts A, B, and C: Objective Response Rate (ORR)
• Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT)
• Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity
• Cohorts D and E: Number of Participants with Adverse Events (AE)
• Cohorts D and E: Number of Participants with Laboratory Values Abnormalities
• Cohorts D and E: Number of Participants with Vital Signs Abnormalities

Secondary Outcome:

• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs
• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities
• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities
• Cohorts Ph1b-D, Ph1b-E, D, and E: ORR
• Cohorts Ph1b-D, Ph1b-E, D, and E: Duration of Response (DoR)
• Cohorts Ph1b-D, Ph1b-E, D, and E: Clinical Benefit Rate (CBR)
• Cohorts D and E: Progression Free Survival (PFS)

Colorectal cancer (CRC) is a major global health concern and the third most common cancer worldwide. Amivantamab (also known as RYBREVANT or JNJ-61186372) is a fully human immunoglobulin (Ig) G1-based bispecific antibody (Ab) directed against the epidermal growth factor (EGF) and mesenchymal epithelial transition (MET) receptors, with evidence of preclinical activity against non-small cell lung cancer (NSCLC) tumors with activating EGF receptor (EGFR) mutations, the T790M and C797S second-site resistance EGFR mutations, overexpressed wild-type EGFR, as well as with activation of the MET pathway. Amivantamab has demonstrated activity in both EGFR- and MET-driven NSCLC, with preclinical evidence demonstrating its ability to recruit immune effector cells. While two anti-EGFR antibodies are incorporated as part of the SoC for CRC patients, MET is highly expressed or amplified in subsets of CRC and additionally plays a role in mediating resistance to anti-EGFR treatments. The study consists of up to 28 days screening period, treatment period will begin on Cycle 1 Day 1 (C1D1) (for Cohorts A, B, and C) or C1D -2 (for Ph1b-D, Ph1b-E, Cohorts D and E) with the administration of the study treatment and continue as 28-day cycles until the end of treatment visit, up to 30 days after discontinuation of study treatment. The safety of amivantamab as a monotherapy or in addition to SoC chemotherapy will be assessed by physical examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status (PS), laboratory tests, vital signs, monitoring of adverse events, and concomitant medication usage. The total duration of this study will be up to 4 years 3 months.

Voir cet essai sur ClinicalTrials.gov