Evaluation of Amivantamab Monotherapy and Combination with Standard Chemotherapy in Advanced or Metastatic Colorectal Cancer
- Trial ID
- 2023-506517-22-00
- Protocol
- 61186372GIC2002
- Sponsor
- Janssen Cilag International
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **anti-tumor activity** of amivantamab as a monotherapy and to characterize the safety profile of amivantamab when combined with standard-of-care (SoC) chemotherapy in participants with advanced or metastatic colorectal cancer (mCRC). Additionally, the study aims to determine the recommended phase 2 combination dose (RP2CD) of amivantamab when added to SoC chemotherapy. This is clinically relevant as it seeks to establish the efficacy and safety of amivantamab, potentially offering a new therapeutic option for patients with mCRC.
Participants
The clinical trial involves a total of **95 participants** diagnosed with **Advanced or Metastatic Colorectal Cancer**. The study population includes both male and female subjects, aged 18 years and older, encompassing a vulnerable population. Participants were selected based on specific criteria, including a confirmed diagnosis of unresectable or metastatic adenocarcinoma of the colon or rectum, with tumors characterized as having wildtype KRAS, NRAS, BRAF, and without evidence of ERBB2/HER2 amplification. The trial requires participants to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must also have adequate organ and bone marrow function and agree to adhere to specified lifestyle restrictions. The trial does not specify particular lifestyle considerations such as diet or physical activity beyond these requirements. Key inclusion criteria include the ability to provide informed consent and adherence to contraceptive measures for both male and female participants of childbearing potential. The trial aims to assess the anti-tumor activity and safety of amivantamab in combination with standard-of-care chemotherapy.
Plans and Procedures
The clinical trial is designed to evaluate the **anti-tumor activity** and safety of **amivantamab** as a monotherapy and in combination with standard-of-care chemotherapy in participants with advanced or metastatic colorectal cancer. This study is structured as a Phase 1b/2, open-label trial. The trial will assess the recommended phase 2 combination dose of amivantamab when added to standard chemotherapy. The trial is expected to commence recruitment on July 1, 2022, and conclude by March 23, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, previous diagnosis of unresectable or metastatic adenocarcinoma of the colon or rectum, and adequate organ function. The trial will include follow-up visits to monitor the **objective response rate** and safety of the treatment. The end-of-study visit will evaluate the overall outcomes and any adverse effects experienced by the participants.
The expected duration of participant involvement will vary depending on individual response to treatment and the specific phase of the trial they are enrolled in. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with study protocols, or if the investigator deems it necessary for their safety. The trial will ensure that all participants adhere to specified lifestyle restrictions and contraceptive measures to mitigate any potential risks associated with the study treatments.
Treatment
The clinical trial involves the administration of several experimental and non-experimental treatments. **Amivantamab**, marketed under the product name JNJ-61186372, is a **solution for infusion** used as the primary investigational drug. It is administered intravenously. The active substance, amivantamab, is a protein-based compound provided by Janssen-Cilag International N.V. This investigational drug is utilized to assess its anti-tumor activity as a monotherapy and in combination with standard-of-care chemotherapy in participants with advanced or metastatic colorectal cancer.
**Oxaliplatin**, marketed as Oxaliplatin Hikma 5 mg/ml, is a **solution for infusion**. It is administered intravenously and is used as part of the standard-of-care chemotherapy regimen. The active substance, oxaliplatin, is a chemical compound provided by Hikma Farmacêutica (Portugal), S.A. This drug is repackaged and labeled specifically for clinical trial use.
**Folinic Acid**, available under the product names BENDAFOLIN 10 mg/ml and Ribofolin® 10 mg/ml, is a **solution for injection**. It is administered intravenously and serves as an auxiliary treatment in the chemotherapy regimen. The active substance, folinic acid, is a chemical compound provided by Bendalis GmbH and Hikma Farmacêutica (Portugal), S.A., respectively. The vials are labeled and repackaged for clinical trial purposes.
**Irinotecan Hydrochloride Trihydrate**, marketed as Irinotecan Hikma 20 mg/ml, is a **solution for infusion**. It is administered intravenously as part of the chemotherapy regimen. The active substance, irinotecan hydrochloride trihydrate, is a chemical compound provided by Hikma Farmacêutica (Portugal), S.A. The product is prepared and labeled for clinical trial use.
**Fluorouracil**, available under the product names 5-FU medac 50 mg/ml and Fluorouracil Hikma 50 mg/ml, is a **solution for injection**. It is administered intravenously as part of the chemotherapy regimen. The active substance, fluorouracil, is a chemical compound provided by Medac Gesellschaft für klinische Spezialpräparate mbH (Wedel) and Hikma Farmacêutica (Portugal), S.A. The vials are labeled and repackaged for clinical trial purposes.
**Anhydrous Calcium Folinate**, marketed as Calcium Folinate, is used as an auxiliary treatment in the chemotherapy regimen. It is administered intravenously. The active substance, anhydrous calcium folinate, is a chemical compound. The product is prepared and labeled for clinical trial use.
All treatments are administered intravenously, and compliance with dosing schedules is monitored throughout the trial. The investigational and auxiliary drugs are labeled with clinical label booklets and repackaged in cartons for use in the clinical trial. The trial aims to evaluate the safety and efficacy of amivantamab in combination with standard-of-care chemotherapy in participants with metastatic colorectal cancer.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**. This endpoint will evaluate the proportion of participants with a predefined reduction in tumor size, as determined by imaging studies, following treatment with amivantamab, both as a monotherapy and in combination with standard-of-care chemotherapy. The trial aims to assess the anti-tumor activity of amivantamab in participants with advanced or metastatic colorectal cancer.
Data collection for efficacy assessment will be conducted at specified intervals throughout the trial, with imaging studies performed to measure tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The trial will also determine the recommended phase 2 combination dose (RP2CD) of amivantamab when added to standard-of-care chemotherapy. The analysis of efficacy data will be performed using validated statistical methods to ensure the reliability and accuracy of the results.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place).
- Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum.
- 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.
- 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.
- Participant must have ECOG PS 0 or 1.
- 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.
- Participant must have a tumor lesion amenable for biopsy and agree to mandatory protocol-defined screening biopsies.
- Human immunodeficiency virus (HIV)-positive participants are eligible if they meet the criteria
- 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.
- A female participant must be either not of childbearing potential, or of childbearing potential and practicing at least 1 highly effective method of contraception.
- 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.
- 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.
- 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.
- 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.
- Participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
- 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
- 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.
- Participant with known dMMR/MSI-H status who has not received immunotherapy treatments per local SoC guidelines.
- Participant has an uncontrolled illness
- Participant with symptomatic or untreated brain metastasis
- History or known presence of leptomeningeal disease
- 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.
- Participant has a history of clinically significant cardiovascular disease.
- 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)
- 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
- 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.
- 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.
- 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).
- 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
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 01 Jul 2022 | 8 |
 Germany | Recruiting | 01 Jul 2022 | 2 |
 Italy | Recruiting | 01 Jul 2022 | 9 |
 Spain | Recruiting | 01 Jul 2022 | 18 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Irinotecan Hikma 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Other | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | — | — | PRD6796264 |
Oxaliplatin Hikma 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Other | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | — | — | PRD9467155 |
FLUOROURACIL | Other | PHF00230MIG | INTRAVENOUS USE | — | — | SCP7587892 |
IRINOTECAN | Other | PHF00230MIG | INTRAVENOUS USE | — | — | SCP204065 |
Fluorouracil Hikma 50 mg/ml Injektionslösung | Other | INJEKTIONSLÖSUNG | INTRAVENOUS USE | — | — | PRD7117395 |
Ribofolin® 10 mg/ml Injektionslösung | Other | INJEKTIONSLÖSUNG | INTRAVENOUS USE | — | — | PRD10286539 |
JNJ-61186372 | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | — | — | PRD9813175 |
OXALIPLATIN | Other | PHF00230MIG | INTRAVENOUS USE | — | — | SCP1891954 |
CALCIUM FOLINATE | Other | PHF00169MIG | INTRAVENOUS USE | — | — | SCP26549405 |
JNJ-61186372 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | — | — | PRD11078981 |