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
Description
Brief Summary
The purpose of this study is to assess the anti-tumor 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).
Detailed Description
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.
Phase
N/AInclusion and Exclusion Criteria
- - Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum - For Phase 1 dose confirmation cohorts (Cohorts Ph1b-D and Ph1b-E): Participant must have evaluable disease. For Phase 2 dose expansion cohorts (Cohorts D and E): Participant must have measurable disease according to Response Criteria in Solid
- If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed greater than or equal to (>=) 7 days after the biopsy - Participant must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 - Participant must have a tumor lesion amenable for biopsy and agree to mandatory protocol-defined screening biopsy - A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study. Note: Participant must not be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study
- Participant with identified mutation in Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), or epidermal growth factor receptor (EGFR) ectodomain, or ERBB2/HER2 amplification by central circulating tumor deoxyribonucleic acid (ctDNA) testing at screening
- Participant with symptomatic or untreated brain metastasis
- History or known presence of leptomeningeal disease
- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
Sites
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.
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