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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05379595

Collaborator

(none)

225

Enrollment

Locations

Arms

51.1

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study 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).

Condition or Disease	Intervention/Treatment	Phase
Advanced or Metastatic Colorectal Cancer	Drug: Amivantamab Biological: Fluorouracil Biological: Leucovorin Biological: Oxaliplatin Biological: Irinotecan	Phase 1/Phase 2

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 1 month.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

225 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 29, 2022

Anticipated Primary Completion Date :

Oct 30, 2026

Anticipated Study Completion Date :

Oct 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohorts A, B, and C: Amivantamab Monotherapy Participants with left-sided colorectal cancer (CRC) in Cohort A (no prior anti-epidermal growth factor receptor [EGFR] therapy) and in Cohort B (post anti-EGFR therapy), and right-sided CRC in Cohort C (with or without anti-EGFR therapy), will be administered intravenous (IV) infusion of amivantamab 1050 milligrams (mg) if body weight (BW) is less than (<) 80 kilograms (kg) or 1400 mg if BW is greater than or equal to (>=) 80 kg, as monotherapy on Days 1 and 15 of Cycle 2 (28-days cycle).	Drug: Amivantamab Amivantamab will be administered as intravenous infusion. Other Names: RYBREVANT JNJ-61186372
Active Comparator: Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Participants who are anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab 1050 or 700 mg (dose level 0 [DL0]) if BW is <80 kg, or 1400 or 1050 mg (dose de-escalation [DL-1]) if BW is >= 80 kg, on Days -1, -2, 8 and 22 of Cycle 1 and along with mFOLFOX6 SOC chemotherapy on Days 1 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 (each cycle of 28 days) in Phase 1b dose confirmation Cohort (Cohort Ph1b-D). Participant in Phase 2 Cohort (Cohort D) will receive recommended Phase 2 combination dose (RP2CD) of amivantamab along with mFOLFOX6 SOC chemotherapy determined in Cohort Ph1b-D.	Drug: Amivantamab Amivantamab will be administered as intravenous infusion. Other Names: RYBREVANT JNJ-61186372 Biological: Fluorouracil Fluorouracil will be administered as intravenous infusion. Biological: Leucovorin Leucovorin will be administered as intravenous infusion. Biological: Oxaliplatin Oxaliplatin will be administered as intravenous infusion.
Active Comparator: Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Participants who are anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab along with FOLFIRI SOC chemotherapy on Days -1, -2, and 8 of Cycle 1 and Days 1 and 15 of Cycle 2 in Ph1b-E. For Cohort E, RP2CD determined in Ph1b-E will be administered.	Drug: Amivantamab Amivantamab will be administered as intravenous infusion. Other Names: RYBREVANT JNJ-61186372 Biological: Fluorouracil Fluorouracil will be administered as intravenous infusion. Biological: Leucovorin Leucovorin will be administered as intravenous infusion. Biological: Irinotecan Irinotecan will be administered as intravenous infusion.

Arm

Intervention/Treatment

Experimental: Cohorts A, B, and C: Amivantamab Monotherapy

Participants with left-sided colorectal cancer (CRC) in Cohort A (no prior anti-epidermal growth factor receptor [EGFR] therapy) and in Cohort B (post anti-EGFR therapy), and right-sided CRC in Cohort C (with or without anti-EGFR therapy), will be administered intravenous (IV) infusion of amivantamab 1050 milligrams (mg) if body weight (BW) is less than (<) 80 kilograms (kg) or 1400 mg if BW is greater than or equal to (>=) 80 kg, as monotherapy on Days 1 and 15 of Cycle 2 (28-days cycle).

Drug: Amivantamab

Amivantamab will be administered as intravenous infusion.

Other Names:

RYBREVANT

JNJ-61186372

Active Comparator: Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6)

Participants who are anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab 1050 or 700 mg (dose level 0 [DL0]) if BW is <80 kg, or 1400 or 1050 mg (dose de-escalation [DL-1]) if BW is >= 80 kg, on Days -1, -2, 8 and 22 of Cycle 1 and along with mFOLFOX6 SOC chemotherapy on Days 1 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 (each cycle of 28 days) in Phase 1b dose confirmation Cohort (Cohort Ph1b-D). Participant in Phase 2 Cohort (Cohort D) will receive recommended Phase 2 combination dose (RP2CD) of amivantamab along with mFOLFOX6 SOC chemotherapy determined in Cohort Ph1b-D.

Drug: Amivantamab

Amivantamab will be administered as intravenous infusion.

Other Names:

RYBREVANT

JNJ-61186372

Biological: Fluorouracil

Fluorouracil will be administered as intravenous infusion.

Biological: Leucovorin

Leucovorin will be administered as intravenous infusion.

Biological: Oxaliplatin

Oxaliplatin will be administered as intravenous infusion.

Active Comparator: Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)

Participants who are anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab along with FOLFIRI SOC chemotherapy on Days -1, -2, and 8 of Cycle 1 and Days 1 and 15 of Cycle 2 in Ph1b-E. For Cohort E, RP2CD determined in Ph1b-E will be administered.

Drug: Amivantamab

Amivantamab will be administered as intravenous infusion.

Other Names:

RYBREVANT

JNJ-61186372

Biological: Fluorouracil

Fluorouracil will be administered as intravenous infusion.

Biological: Leucovorin

Leucovorin will be administered as intravenous infusion.

Biological: Irinotecan

Irinotecan will be administered as intravenous infusion.

Outcome Measures

Primary Outcome Measures

Cohorts A, B, and C: Objective Response Rate (ORR) [Up to 4 years 1 month]
ORR is defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), as defined by investigator assessment using Response Criteria in Solid Tumors (RECIST) version 1.1.
Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT) [Up to 4 years 1 month]
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity [Up to 4 years 1 month]
Number of participants with DLT by severity will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death related to adverse event.
Cohorts D and E: Number of Participants with Adverse Events (AE) [Up to 4 years 1 month]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Cohorts D and E: Number of Participants with Laboratory Values Abnormalities [Up to 4 years 1 month]
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Cohorts D and E: Number of Participants with Vital Signs Abnormalities [Up to 4 years 1 month]
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.

Secondary Outcome Measures

Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs [Up to 4 years 1 month]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities [Up to 4 years 1 month]
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities [Up to 4 years 1 month]
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.
Cohorts Ph1b-D, Ph1b-E, D, and E: ORR [Up to 4 years 1 month]
ORR is defined as the percentage of participants who achieve either a PR or CR, as defined by investigator assessment using RECIST version 1.1.
Cohorts Ph1b-D, Ph1b-E, D, and E: Duration of Response (DoR) [Up to 4 years 1 month]
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR, as defined by investigator assessment using RECIST version 1.1.
Cohorts Ph1b-D, Ph1b-E, D, and E: Clinical Benefit Rate (CBR) [Up to 4 years 1 month]
CBR is defined as the percentage of participants achieving complete or partial response, as well as durable stable disease (defined as a duration of at least 11 weeks) as defined by RECIST version 1.1.
Cohorts D and E: Progression Free Survival (PFS) [Up to 4 years 1 month]
PFS is defined as the time from the first administration of study treatment until the date of objective disease progression or death, whichever comes first, based on investigator assessment using RECIST version 1.1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion 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 Tumors (RECIST) Version 1.1. 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

Exclusion Criteria:

Participant with known Erb-B2 receptor tyrosine kinase 2 (ERBB2)/ human epidermal growth factor receptor 2 (HER-2) amplification based on the local testing results
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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham - The Kirklin Clinic	Birmingham	Alabama	United States	35294
2	City of Hope	Duarte	California	United States	91010
3	University of Southern California	Los Angeles	California	United States	90033
4	Los Angeles VA Health Care System	Los Angeles	California	United States	90073
5	University of California, Los Angeles UCLA	Los Angeles	California	United States	90404
6	University of Colorado - Anschutz Medical Campus	Aurora	Colorado	United States	80045
7	Georgetown University Hospital	Washington	District of Columbia	United States	20007
8	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
9	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
10	University of Michigan Health System	Ann Arbor	Michigan	United States	48103
11	Cancer & Hematology Centers of Western Michigan, PC	Grand Rapids	Michigan	United States	49503
12	NYU Langone Long Island Clinical Research Associates	New York	New York	United States	10016
13	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
14	Mayo Clinic Rochester	Rochester	New York	United States	55905
15	Duke Cancer Institute	Durham	North Carolina	United States	27710
16	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee	United States	37232
17	MD Anderson Cancer Center	Houston	Texas	United States	77030
18	McGuire Veterans Affairs Medical Center	Richmond	Virginia	United States	23059
19	University of Washington	Seattle	Washington	United States	98195
20	Institut Jules Bordet	Anderlecht		Belgium	1070
21	Cliniques Universitaires Saint-Luc	Brussel		Belgium	1200
22	UZ Antwerpen	Edegem		Belgium	2650
23	Universitair Ziekenhuis Gasthuisberg	Leuven		Belgium	3000
24	Jilin cancer hospital	Changchun		China	130103
25	Sichuan University West China Hospital Cancer Center	Chengdu		China	610041
26	The Second Hospital To Dalian Medical University	Da Lian Shi		China	116023
27	Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital	Guangzhou		China	510655
28	No.1 Affiliated Hospital, Medical College of Zhejiang University	Hangzhou		China	310003
29	The Second Affiliated Hospital of Zhejiang University College of Medicine	Hangzhou		China	310003
30	Fudan University Shanghai Cancer Center	Shanghai		China	201321
31	Hubei province tumor hospital	Wu Han Shi		China	430079
32	Centre Hospitalier Regional Universitaire Besancon	Besancon		France	25030
33	Centre Georges François Leclerc	Dijon		France	21000
34	Centre Jean Bernard - Clinique Victor Hugo	Le Mans		France	72000
35	Centre Leon Bérard	Lyon Cedex 8		France	69008
36	CHU De Poitiers	Poitiers		France	86000
37	Helios Kliniken Berlin Buch Gmbh	Berlin		Germany	13125
38	Katholisches Klinikum Bochum gGmbH	Bochum		Germany	44791
39	Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus	Frankfurt		Germany	60389
40	Asklepios Klinik Altona	Hamburg		Germany	22763
41	Ludwig-Maximilians-Universitaet Muenchen	Munich		Germany	81377
42	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
43	A.O. Ospedale Niguarda Ca' Granda	Milano		Italy	20162
44	Fondazione G. Pascale - Istituto Nazionale Tumori IRCCS	Napoli		Italy	80131
45	Istituto Oncologico Veneto - IRCCS	Padova		Italy	35128
46	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56126
47	Seoul National University Hospital	Seoul		Korea, Republic of	03080
48	Asan Medical Center	Seoul		Korea, Republic of	05505
49	Samsung Medical Center	Seoul		Korea, Republic of	06351
50	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
51	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	3722
52	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
53	Hospital Umum Sarawak	Kuching		Malaysia	93586
54	Beacon Hospital Sdn. Bhd.	Petaling Jaya		Malaysia	46050
55	Ad-Vance Medical Research	Ponce		Puerto Rico	00717
56	Pan American Center for Oncology Trials LLC	Rio Piedras		Puerto Rico	00935
57	Hosp. Univ. Vall D Hebron	Barcelona		Spain	08035
58	Hosp. Gral. Univ. Gregorio Marañon	Madrid		Spain	28007
59	Hosp. Univ. Ramon Y Cajal	Madrid		Spain	28034
60	Hosp. Univ. Fund. Jimenez Diaz	Madrid		Spain	28040
61	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
62	Hosp. Univ. Hm Sanchinarro	Madrid		Spain	28050
63	Hosp. Univ. Marques de Valdecilla	Santander		Spain	39008
64	Hosp. Clinico Univ. de Valencia	Valencia		Spain	46010
65	Changhua Christian Hospital	Changhua		Taiwan	500
66	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	83301
67	Chi Mei Medical Center - Liu Ying	Liou Ying Township		Taiwan	736
68	National Cheng Kung University Hospital	Tainan		Taiwan	704
69	National Taiwan University Hospital	Taipei		Taiwan	10002
70	Linkou Chang Gung Memorial Hospital	Taoyuan		Taiwan	33305
71	Bristol Haematology and Oncology Centre	Bristol		United Kingdom	BS2 8ED
72	Royal Marsden Hospital	London		United Kingdom	SW3 6JJ
73	Imperial College London and Imperial College Healthcare NHS Trust	London		United Kingdom	W12 0HS
74	Royal Marsden Hospital	Sutton		United Kingdom	SM2 5PT