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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Aug 2022 → ongoing

Decision date (initial)

2024-01-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Research and Development

External identifiers

EU CT number

2023-506517-22-00

EudraCT number

2021-006629-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Efficacy, Pharmacodynamic, Pharmacokinetic, Safety

To assess the anti-tumor activity of amivantamab IV as a monotherapy in participants with mCRC (Ph2 Amivantamab IV Monotherapy), Confirm the RP2CD of amivantamab when added to the SoC chemotherapy (Ph1b Amivantamab IV+Chemotherapy Dose Confirmation), To characterize the safety of amivantamab IV when added to SoC chemotherapy in participants with right-sided mCRC (Ph2 Amivantamab IV+Chemotherapy), To characterize the safety of amivantamab SC when added to SoC chemotherapy in participants with mCRC (Ph2 Amivantamab SC+Chemotherapy)

Conditions and MedDRA coding

Advanced or Metastatic Colorectal Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. Participant must be ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place).
2. 2. Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum.
3. 3.Participant must have tumor previously characterized as having wildtype KRAS, NRAS, BRAF and without evidence of ERBB2/HER2 amplification. Evaluation of dMMR/MSI-H status is also required in accordance with local guidelines and SoC.
4. 4. For Ph1b-D and Ph1b-E: Participant must have evaluable disease. For Ph 2: Participant must have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed ≥7 days after the biopsy.
5. 5. Participant must have ECOG PS 0 or 1.
6. 6. Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony stimulating factor (G-CSF) within 7 days prior to the date of the laboratory test.
7. 7. Participant must have a tumor lesion amenable for biopsy and agree to mandatory protocol-defined screening biopsies.
8. 8. Human immunodeficiency virus (HIV)-positive participants are eligible if they meet the criteria
9. 9. 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.
10. 10. A female participant must be either not of childbearing potential, or of childbearing potential and practicing at least 1 highly effective method of contraception.
11. 11. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
12. 12. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. If partner is a female of childbearing potential, the male participant must use condoms, and the partner must also be practicing a highly effective method of contraception. A male participant who is vasectomized must still use a condom, but the partner is not required to use contraception.
13. 13. A male participant must agree not to donate sperm for the purposes of reproduction during the study and for 6 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility.
14. 14. Participant must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
15. 15. Participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
16. 16. Participant may have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). Must be reviewed and agreed to with medical monitor.

Exclusion criteria 14

1. 1. Cohorts A, B, C, Ph1b-D, D, Ph1b-E, and E; Participant with identified mutation in KRAS, NRAS, BRAF, or EGFR ectodomain, or ERBB2/HER2 amplification by central ctDNA testing at screening. Cohort F: Participant with identified mutation in KRAS, NRAS, BRAF V600, or PTEN, identified fusions in ALK, ROS-1, RET, and NTRK-1, ERBB2/HER2 amplification, or identified to have MSI-H status by central ctDNA testing at screening. Note: Central testing must be conducted with a validated test in a CAP/CLIA certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States) in accordance with site SoC. In the European Union, the central test ectodomain, or ERBB2/HER2 amplification by central ctDNA testing at screening must be CE Marked or an in-house test from health institutions in the European Union in accordance with Article 5(5) of the IVDR 2071/746, as amended.
2. 2. Participant with known dMMR/MSI-H status who has not received immunotherapy treatments per local SoC guidelines.
3. 3. Participant has an uncontrolled illness
4. 4. Participant with symptomatic or untreated brain metastasis
5. 5. History or known presence of leptomeningeal disease
6. 6. Participant has a history of (non-infectious) ILD/pneumonitis/pulmonary fibrosis, or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening.
7. 7. Participant has a history of clinically significant cardiovascular disease.
8. 8. Participant has known allergies, hypersensitivity, or intolerance to excipients of: a. amivantamab (refer to the IB, all participants) b. 5-FU or leucovorin (Participants in Ph1b-D, Ph1b-E, and Ph2 Cohorts D and E) c. Oxaliplatin (Participants in Ph1b-D and Ph2 Cohort D) d. Irinotecan (Participants in Ph1b-E and Ph2 Cohort E)
9. 9. Participant has at screening: a. Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) Exception: Participants with a prior history of HBV demonstrated by positive hepatitis B core antibody (HBcAb) are eligible if they have at screening 1) a negative HBsAg and 2) an HBV DNA (viral load) below the lower limit of quantification, per local testing. Participants with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing. b. Positive hepatitis C antibody (anti-HCV [hepatitis C virus]) c. Other clinically active infectious or non-infectious liver disease
10. 10. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
11. 11. Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives, whichever is longer, before the first administration of study drug. Participants must not have received any anti-EGFR treatment within 28 days of the first dose of study drug.
12. 12. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less prior to the first dose of study treatment (except for alopecia or postradiation skin changes [any grade], Grade ≤2 peripheral neuropathy, and Grade ≤2 hypothyroidism stable on hormone replacement).
13. 13. Participant has, or will have, any of the following: a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before the first administration of study treatment. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to the first administration of study treatment, as long as the participant has adequately recovered from the procedure prior to the first dose of study treatment in the clinical judgement of the investigator b. Significant traumatic injury within 3 weeks before the start of the first administration of study treatment (all wounds must be fully healed prior to Day 1) c. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study treatment
14. 14. Participant has received an investigational drug (including investigational vaccines, but not including anti-cancer therapy) or used an invasive investigational medical device within 6 weeks before the planned first dose of study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 17

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications