A phase 1b/2, open-label study of amivantamab monotherapy and amivantamab in addition to standard of care therapeutic agents in participants with recurrent/metastatic head and neck squamous cell carcinoma
| ISRCTN | ISRCTN98745687 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN98745687 |
| ClinicalTrials.gov (NCT) | NCT05379595 |
| Clinical Trials Information System (CTIS) | 2023-508418-40 |
| Integrated Research Application System (IRAS) | 1009340 |
| Protocol serial number | 61186372HNC2002, IRAS 1009340, CPMS 58135 |
| Sponsor | Janssen-Cilag International NV |
| Funder | Janssen-Cliag International NV |
- Submission date
- 05/01/2024
- Registration date
- 12/03/2024
- Last edited
- 30/12/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Head and neck squamous cell cancer (HNSCC) develops from the mucosal epithelium of the mouth, nose, and throat. HNSCC represents a significant global health concern and despite recent advances in its treatment, the overall survival rates have not substantially improved in the past few decades. While many patients initially present with localized disease, approximately 50% of patients will experience local recurrence or distant metastasis within 5 years.
Amivantamab (JNJ-61186372) is a human immunoglobulin G1 (IgG1)-based antibody (a protein that helps protect the body against a foreign trigger) that simultaneously inhibits the activity of two proteins, epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET), which are known to play crucial roles in the development and progression of HNSCC, promote tumor growth, and impact development of resistance to available therapies.
The Sponsor aims to evaluate if amivantamab as monotherapy and in addition to pembrolizumab, or paclitaxel, or pembrolizumab plus carboplatin demonstrates anti-tumor activity with a tolerable safety profile.
Who can participate?
Patients >=18 years of age with head and neck squamous cell carcinoma.
What does the study involve?
The study will be conducted as below:
1. Screening (28 days)
2. Treatment Phase: Participants will receive 1 of the below study treatment(s) on Day 1 of each 21-day cycle:
• Amivantamab subcutaneous (SC)
• Amivantamab SC + pembrolizumab intravenous infusion
• Amivantamab SC + paclitaxel intravenous infusion
• Amivantamab SC + pembrolizumab and carboplatin intravenous infusion
• Amivantamab SC + pembrolizumab intravenous infusion before and after the surgery.
3. Post-treatment Follow-up Phase: Participants will be followed-up for safety until last study-related procedure or until 30 days after last dose of amivantamab SC or paclitaxel or carboplatin, or 100 days after the last dose of pembrolizumab (whichever is longer).
During the study, some tests will be performed such as blood tests, physical examinations, vital signs, and electrocardiograms. Blood samples will be taken at multiple timepoints to see how the body responds to treatment. Disease status will be checked based on solid tumor response evaluation criteria (RECIST version 1.1).
What are the possible benefits and risks of participating?
Based upon the pathophysiology of HNSCC, the mechanisms of action of amivantamab, and prior clinical experience, there is potential benefit to participants of this study in regards to improved outcomes of R/M HNSCC.
Participants may experience some benefit from participation in the study that is not due to receiving study drug, but due to regular visits and assessments monitoring overall health. Participation may help other people with HNSCC in the future.
Participants may have side effects from the study treatments or procedures required in this study that may be mild to severe and even life-threatening, and they can vary from person to person. The potential risks include allergic and anaphylactic-like reactions and hypersensitivity, lung and skin related issues, colitis, liver toxicity, myelosuppression (condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets), renal toxicity and neurologic toxicity after getting the study drug. There are other, less frequent risks. The participant information sheet and informed consent form, which must be signed by all participants, includes a detailed section outlining the potential risks associated with study participation.
Not all possible side effects and risks related to amivantamab may be known at this moment. During the study, the Sponsor may learn new information about amivantamab. The study doctor will inform participants as soon as possible about any new information that such as unforeseen risks.
To minimise the risk associated with taking part in the study, participants will be frequently assessed for any side effects and other medical events. Participants are educated to report any such events to the study doctor, who will provide appropriate medical care. Any serious side effects that are reported to the sponsor are thoroughly reviewed by a specialist drug safety team.
There are no costs to participants to be in the study. The sponsor will pay for the study drug and tests that are part of the study. The participant will receive reasonable reimbursement for study-related costs (for example, travel/parking costs).
Where is the study run from?
Janssen-Cliag International NV (Netherlands)
When is the study starting and how long is it expected to run for?
January 2024 to June 2027
Who is funding the study?
Janssen-Cliag International NV (Netherlands)
Who is the main contact?
Participate-In-This-Study@its.jnj.com
Contact information
Scientific
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
Principal investigator
Downs Road
London
SM52 5PT
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional non randomized |
| Secondary study design | Non randomised study |
| Scientific title | A phase 1b/2, open-label study of amivantamab monotherapy and amivantamab in addition to standard of care therapeutic agents in participants with recurrent/metastatic head and neck squamous cell carcinoma |
| Study acronym | OrigAMI-4 |
| Study objectives | Current study objectives: Main objectives: In participants with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), to assess anti-tumor activity of: • Amivantamab alone in participants who have received prior platinum-based chemotherapy and programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) therapy. • Amivantamab in addition to paclitaxel for participants who received prior programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) based therapy. • Amivantamab in addition to pembrolizumab or in addition to pembrolizumab and carboplatin who are treatment-naïve in the R/M setting. • To assess the recommended phase 2 combination dose (RP2CD) as well as safety and tolerability of amivantamab in addition to paclitaxel in participants who received prior PD- 1/PD-L1 therapy. In participants with resectable locally advanced (L/A) HNSCC, to assess anti-tumor activity of: • Amivantamab in addition to pembrolizumab before and after the surgery (perioperative). Secondary objectives: In participants with R/M HNSCC, to assess the safety, tolerability, and additional measures of efficacy of: • Amivantamab alone in participants who have received prior platinum-based chemotherapy and programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) therapy. Measures of pharmacokinetics (what the body does to the drug) will also be assessed for amivantamab alone. • Amivantamab in addition to paclitaxel for participants who have received prior programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) therapy. • Amivantamab in addition to pembrolizumab or in addition to pembrolizumab and carboplatin who are treatment-naïve in the R/M setting. In participants with resectable L/A HNSCC, to assess anti-tumor activity, safety and tolerability of: • Amivantamab in addition to pembrolizumab before and after the surgery. Previous study objectives: Main objectives: In participants with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), to assess anti-tumor activity of: •Amivantamab alone in participants who have received prior platinum-based chemotherapy and programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) therapy •Amivantamab in addition to paclitaxel for participants who received prior programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) based therapy • Amivantamab in addition to pembrolizumab or in addition to pembrolizumab and carboplatin who are treatment-naïve in the R/M setting. •To assess the recommended phase 2 combination dose (RP2CD) as well as safety and tolerability of amivantamab in addition to paclitaxel in participants who received prior PD- 1/PD-L1 therapy. Secondary objectives: In participants with R/M HNSCC, to assess the safety, tolerability, and additional measures of efficacy of •Amivantamab alone in participants who have received prior platinum-based chemotherapy and programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) therapy. Measures of pharmacokinetics (what the body does to the drug) will also be assessed for amivantamab alone. •Amivantamab in addition to paclitaxel for participants who have received prior programmed death receptor-1 (PD-1)/ligand 1 (PD-L1) therapy • Amivantamab in addition to pembrolizumab or in addition to pembrolizumab and carboplatin who are treatment-naive in the R/M setting. Original study objectives: The primary objectives of each cohort are: Cohort 1: To assess anti-tumour activity of amivantamab monotherapy in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who have received prior treatment with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor. Cohort 2: To assess anti-tumour activity of amivantamab in addition to pembrolizumab in participants with R/M HNSCC who are treatment-naïve in the R/M setting. Cohort 3: To determine recommended Phase 2 (combination) dose(s) (RP2CDs) of amivantamab in addition to paclitaxel in participants with R/M HNSCC who have received PD-1/PD-L1 based therapy; and, to characterise safety and tolerability of amivantamab in addition to paclitaxel in participants with R/M HNSCC who have received PD-1/PD-L1 based therapy. Cohort 3B: To assess anti-tumour activity of amivantamab in addition to paclitaxel in participants with R/M HNSCC who have received PD-1/PD-L1 based therapy. The secondary objectives for each cohort include: Cohort 1: To further assess anti-tumour activity of amivantamab monotherapy in participants with R/M HNSCC who have received prior treatment with platinum-based chemotherapy (PBC) and a PD-1/PD-L1 inhibitor. Cohort 2: To further assess anti-tumour activity of amivantamab in addition to pembrolizumab in participants with R/M HNSCC who are treatment-naïve in the R/M setting. Cohort 3B: To further assess anti-tumour activity of amivantamab in addition to paclitaxel in participants with R/M HNSCC who have received PD-1/PD-L1 based therapy. |
| Ethics approval(s) |
Approved 11/03/2024, London - Westminster Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; westminster.rec@hra.nhs.uk), ref: 24/LO/0090 |
| Health condition(s) or problem(s) studied | Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma |
| Intervention | Current interventions, as of 31/03/2025: Experimental: Cohort 1 Amivantamab Monotherapy (Dose Expansion) Participants will receive subcutaneous injection of amivantamab monotherapy 1600 milligrams (mg) (2240 mg, if body weight >=80 kilograms [kg]) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) once every week (q1w) for the remainder of Cycle 1 (Days 8 and 15), and every 3 weeks (q3w) from Cycle 2 onwards. Experimental: Cohort 2 Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in) Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle). Experimental: Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) in dose confirmation Cohort 3A. The recommended Phase 2 combination dose (RP2CD) of amivantamab will be determined in conjunction with study evaluation team (SET) in this dose confirmation Cohort 3A. Experimental: Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel Participants will receive subcutaneous injection of amivantamab at the determined RP2CD in addition to intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) as confirmed by SET in Cohort 3A. Experimental: Cohort 4 Amivantamab Monotherapy: Participants will receive subcutaneous injection of amivantamab monotherapy 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards. Experimental: Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion). Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards in addition to intravenous injection of pembrolizumab 200 mg on Day 1 of each cycle, and carboplatin (area under the concentration-time curve [AUC] 5 milligram per milliliter [mg/ml]*min) q3w on Day 1 of Cycles 1-6. _____ Previous interventions as of 26/11/2024: Experimental: Cohort 1 Amivantamab Monotherapy (Dose Expansion) Participants will receive subcutaneous injection of amivantamab monotherapy 1600 milligrams (mg) (2240 mg, if body weight >=80 kilograms [kg]) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) once every week (q1w) for the remainder of Cycle 1 (Days 8 and 15), and every 3 weeks (q3w) from Cycle 2 onwards. Experimental: Cohort 2 Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in) Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle). Experimental: Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) in dose confirmation Cohort 3A. The recommended Phase 2 combination dose (RP2CD) of amivantamab will be determined in conjunction with study evaluation team (SET) in this dose confirmation Cohort 3A. Experimental: Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel Participants will receive subcutaneous injection of amivantamab at the determined RP2CD in addition to intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) as confirmed by SET in Cohort 3A. Experimental: Cohort 4 Amivantamab Monotherapy: Participants will receive subcutaneous injection of amivantamab monotherapy 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards. _____ Previous interventions: Experimental: Cohort 1 Amivantamab Monotherapy (Dose Expansion) Participants will receive subcutaneous injection of amivantamab monotherapy 1600 milligrams (mg) (2240 mg, if body weight >=80 kilograms [kg]) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) once every week (q1w) for the remainder of Cycle 1 (Days 8 and 15), and every 3 weeks (q3w) from Cycle 2 onwards. Experimental: Cohort 2 Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in) Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle). Experimental: Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) in dose confirmation Cohort 3A. The recommended Phase 2 combination dose (RP2CD) of amivantamab will be determined in conjunction with study evaluation team (SET) in this dose confirmation Cohort 3A. Experimental: Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel Participants will receive subcutaneous injection of amivantamab at the determined RP2CD in addition to intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) as confirmed by SET in Cohort 3A. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Cohort 1/2/3/4: Amivantamab co-formulated with recombinant human hyaluronidase (rHuPH20) [Amivantamab, Vorhyaluronidase alfa] Cohort 5: Amivantamab co-formulated with recombinant human hyaluronidase (rHuPH20) [Amivantamab, Vorhyaluronidase alfa] Biological: Pembrolizumab, Pembrolizumab will be administered intravenously. Other Names: • KEYTRUDA Drug: Carboplatin, Carboplatin will be administered intravenously. Other Names: • PARAPLATIN |
| Primary outcome measure(s) |
Current primary outcome measure as of 31/03/2025: |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 31/03/2025: |
| Completion date | 17/07/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 217 |
| Key inclusion criteria | Current inclusion criteria as of 31/03/2025: 1. Have histologically or cytologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that is considered incurable by local therapies 2. Acceptable prior lines of therapy will be determined according to specific cohort 1, 2, 3A, 3B, 4 and 5: 2.1. The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx 2.2. Any known p16 status of tumor must be negative (Note: All participants with an oropharyngeal tumor must have results of p16 status, per local testing) 2.3. Participants must provide local testing results of programmed cell death ligand 1 (PD-L1) status, if available 3. Cohort 4: 3.1. Patients must have primary tumor location in oropharynx. Unknown primary tumors are not included 3.2. Primary tumor must be HPV-positive, confirmed by positive p16 test or high-risk human papillomavirus (HPV) in-situ hybridization (ISH) in tissue (current or archival) 3.3. Participants must provide local testing results of PD-L1 status, if available 4. Participants in Cohorts 1, 2, 3B, 4 and 5 must have measurable disease according to RECIST version 1.1. 5. Participants in Cohort 3A must have evaluable disease (defined as having at least 1 non-target lesion according to RECIST version 1.1 6. 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 post-radiation skin changes [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy and Grade <= 2 hypothyroidism stable on hormone replacement) 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 8. 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 within 7 days prior to the date of the laboratory test. 8. Participants should have: 8.1. Hemoglobin >=9 grams per deciliter (g/dL) 8.2. Neutrophils >=1.5 x 10^3/mcg 8.3. Platelets >=100 x 10^3/mcg _____ Previous participant inclusion criteria as of 26/11/2024: 1. Have histologically or cytologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that is considered incurable by local therapies 2. Acceptable prior lines of therapy will be determined according to specific cohort 1, 2, 3A and 3B: 2.1. The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx 2.2. Any known p16 status of tumor must be negative (Note: All participants with an oropharyngeal tumor must have results of p16 status, per local testing) 2.3. Participants must provide local testing results of programmed cell death ligand 1 (PD-L1) status, if available 3. Cohort 4: 3.1. Patients must have primary tumor location in oropharynx. Unknown primary tumors are not included 3.2. Primary tumor must be HPV-positive, confirmed by positive p16 test or high-risk human papillomavirus (HPV) in-situ hybridization (ISH) in tissue (current or archival) 3.3. Participants must provide local testing results of PD-L1 status, if available 4. Participants in Cohorts 1, 2, and 3B and 4 must have measurable disease according to RECIST version 1.1. 5. Participants in Cohort 3A must have evaluable disease (defined as having at least 1 non-target lesion according to RECIST version 1.1 6. 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 post-radiation skin changes [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy and Grade <= 2 hypothyroidism stable on hormone replacement) 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 8. 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 within 7 days prior to the date of the laboratory test. 8. Participants should have: 8.1. Hemoglobin >=9 grams per deciliter (g/dL) 8.2. Neutrophils >=1.5 x 10^3/mcg 8.3. Platelets >=100 x 10^3/mcg _____ Previous participant inclusion criteria: 1. Be at least 18 years of age at the time of informed consent. 2. Have histologically or cytologically confirmed recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies. 3. Participants must meet the following cohort-specific requirements: Cohort 3A: Dose Confirmation Cohort: Have evaluable disease (defined as having at least 1 non-target lesion according to RECIST v1.1). If only 1 evaluable lesion exists, it may be used for the screening biopsy as long as baseline tumour assessment scans are performed 7 or more days after the biopsy. Tumour lesions situated in a previously irradiated area are considered evaluable if progression following radiation has been demonstrated in such lesions. Cohorts 1, 2, and 3B: Dose Expansion Cohorts: Have measurable disease according to RECIST v1.1. If only 1 measurable lesion exists, it may be used for the screening biopsy as long as baseline tumour assessment scans are performed 7 or more days after the biopsy. Tumour lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions. 4. If available, provide adequate tumour tissue for a baseline sample following the most recent systemic anticancer therapy. 5. Participant may have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). Prior or concurrent second malignancies must be reviewed and agreed to with the medical monitor. 6. 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 post-radiation skin changes [any grade], Grade lower than or equal to 2 peripheral neuropathy and Grade lower than or equal to 2 hypothyroidism stable on hormone replacement). 7. Must meet the protocol defined cohort-specific requirements (See protocol for full details). 8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 9. Have at least 1 of the following: a. Serum creatinine lower than or equal to 1.5 x upper limit of normal (ULN). b. Estimated glomerular filtration rate greater than or equal to 45 millilitre per minute, based on the Modified Diet in Renal Disease (MDRD) 4-variable formula. 10. Participants are eligible if they have the following lab values: a. Aspartate aminotransferase (AST) lower than or equal to 3 x ULN (lower than or equal to 5 x ULN if liver metastases are present) b. ALT lower than or equal to 3 x ULN (lower than or equal to 5 x ULN if liver metastases are present) c. Total bilirubin lower than or equal to 1.5 x ULN; participants with congenital nonhemolytic hyperbilirubinemia such as Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits. 11. Participant must have adequate organ and bone marrow function as per protocol criteria, without history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony-stimulating factor within 7 days prior to the date of the laboratory test. 12. Cohort 2: Thyroid function laboratory values within the normal range. 13. While on study treatment and for 10 months after the last dose of study treatment, a participant must: - Not breastfeed or be pregnant. - Not donate gametes (i.e., eggs or sperm) or freeze for future use for the purposes of assisted reproduction. Participants should consider preservation of gametes prior to study treatment as anticancer treatments may impair fertility. - Wear an external condom. - If of childbearing potential: have a negative highly sensitive serum pregnancy test at screening and within 72 hours of the first dose of study treatment and agree to further pregnancy tests; practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used. - If a participant’s partner is of childbearing potential the partner must practice a highly effective method of contraception unless the participant is vasectomised. 14. Must sign an Informed Consent Form (ICF; or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. 15. Be willing and able to adhere to the lifestyle restrictions specified in this protocol. |
| Key exclusion criteria | Current exclusion criteria as of 31/03/2025: 1. Uncontrolled illness including any medical history or current (non-infectious) interstitial lung disease (ILD)/ pneumonitis/ pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening 2. Participant with untreated brain metastases leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation 3. Participant with a history of clinically significant cardiovascular disease 4. Received 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 treatment. The maximum required washout is 28 days 5. Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment _____ Previous participant exclusion criteria as of 26/11/2024: 1. Uncontrolled illness including any medical history or current (non-infectious) interstitial lung disease (ILD)/ pneumonitis/ pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening 2. Participant with untreated brain metastases leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation 3. Participant with a history of clinically significant cardiovascular disease 4. Received 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 treatment. The maximum required washout is 28 days 5. Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment ______ Previous participant exclusion criteria: 1. Uncontrolled illness, including but not limited to all conditions specified in the protocol. 2. Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis/pulmonary fibrosis, or has current ILD/pneumonitis, or suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening. 3. Known allergies, hypersensitivity, or intolerance to excipients of amivantamab, recombinant human hyaluronidase (rHuPH20), or other study treatment. 4. Participant has a history of clinically significant cardiovascular disease, as specified in the study protocol. 5. 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. 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. 6. Participant with untreated brain metastases 7. Participant has a medical history or known presence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation. 8. HIV-positive participants are not eligible if they meet any of protocol specified criteria. 9. Active hepatitis of infectious origin. 10. Received 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 treatment. The maximum required washout is 28 days. 11. Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment. 12. Requires a prohibited medication that cannot be discontinued, substituted, or temporarily interrupted during the study. 13. Received an investigational treatment (including investigational vaccines, but not including anticancer therapy) or used an invasive investigational medical device within 6 weeks before the planned first dose of study treatment. 14. Cohort 2: Prohibited immunosuppressive medication use within 7 days prior to the first administration of study treatment. 15. Cohort 2: Participant has received a live or live attenuated vaccine within 30 days prior to the first dose of study drug. Vaccines approved or authorised for emergency use and non-live vaccines are allowed. 16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. |
| Date of first enrolment | 14/04/2024 |
| Date of final enrolment | 31/05/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
- France
- Germany
- Korea, South
- Malaysia
- Poland
- Spain
- Taiwan
Study participating centres
London
W12 0HS
England
Downs Road
Sutton
SM2 5PT
England
Hills Road
Cambridge
CB2 0QQ
England
Withington
Manchester
M20 4BX
England
Department of Womens Health
250 Euston Road
London
NW1 2PG
England
Guildford
GU2 7XX
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The data-sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at yoda.yale.edu |
Editorial Notes
30/12/2025: Contact details, study objectives and plain English summary updated.
04/04/2025: Contact details updated.
31/03/2025: The following changes were made to the trial record:
1. The study hypothesis was changed.
2. The interventions were changed.
3. The drug name was changed from "Amivantamab co-formulated with recombinant human hyaluronidase (rHuPH20) [Amivantamab, Vorhyaluronidase alfa]" to "Cohort 1/2/3/4: Amivantamab co-formulated with recombinant human hyaluronidase (rHuPH20) [Amivantamab, Vorhyaluronidase alfa] Cohort 5: Amivantamab co-formulated with recombinant human hyaluronidase (rHuPH20) [Amivantamab, Vorhyaluronidase alfa] Biological: Pembrolizumab, Pembrolizumab will be administered intravenously. Other Names: • KEYTRUDA Drug: Carboplatin, Carboplatin will be administered intravenously. Other Names: • PARAPLATIN".
4. The primary outcome measure was changed.
5. The secondary outcome measures were changed.
6. The inclusion criteria were changed.
7. The exclusion criteria were changed.
8. The recruitment end date was changed from 25/04/2025 to 31/05/2026.
9. The Countries of recruitment France, Germany, Korea, South, Poland, Spain were added.
10. The plain English summary was updated to reflect these changes.
26/11/2024: The following changes were made:
1. Changes were made to the interventions, primary and secondary outcome measures, participant inclusion and exclusion criteria, and the plain English summary.
2. The target number of participants was changed from 117 to 217.
13/05/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 13/05/2024 to 25/04/2025.
2. The overall study end date was changed from 16/11/2026 to 17/07/2026.
3. ClinicalTrials.gov number added.
09/04/2024: The following changes were made:
1. Ethics approval added.
2. The recruitment start date was changed from 18/04/2025 to 13/05/2024.
05/04/2024: Internal review.
05/01/2024: Trial's existence confirmed by NHS HRA.
