A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer (OrigAMI-4)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Squamous Cell Carcinoma of Head and Neck

Treatments: Biological: Amivantamab; Drug: Carboplatin; Drug: Paclitaxel; Biological: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06385080

2023-508418-40-00 (Registry Identifier)

61186372HNC2002

Details and patient eligibility

About

The purpose of this study is to determine safety and preliminary efficacy of amivantamab monotherapy, amivantamab in addition to pembrolizumab, amivantamab in addition to paclitaxel and amivantamab in addition to pembrolizumab and carboplatin in participants with recurrent/metastatic head and neck cancer. The study will also confirm the recommended Phase 2 combination dose (RP2CD) for amivantamab in addition to paclitaxel. The safety and preliminary efficacy of amivantamab in addition to pembrolizumab will also be determined in perioperative (before and after surgery) setting in participants with resectable locally advanced head and neck squamous cell carcinoma (HNSCC).

Enrollment: 287 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cohorts 1 to 5: Have histologically or cytologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that is considered incurable by local therapies or for Cohort 6: have histologically or cytologically confirmed locally advanced (L/A) HNSCC that is considered curable by surgery Acceptable prior lines of therapy will be determined according to specific cohort 1, 2, 3A and 3B: (a) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (b) 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); (c) Participants must provide local testing results of programmed cell death ligand 1 (PD-L1) status, if available; Cohort 4: (d) Patients must have primary tumor location in oropharynx. Unknown primary tumors are not included (e) 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) (f) Participants must provide local testing results of PD-L1 status, if available; Cohort 5 (g) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (h) HPV status must be known (either positive or negative) for patients with primary tumor location in oropharynx with p16 test or high-risk HPV ISH in tissue; (i) Participants must provide local testing results of PD-L1 status; Cohort 6: (j) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (k) 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 Participants must provide local testing results of PD-L1 status (l) Participants must have Stage III or IVa disease (American Joint Committee on Cancer Staging Manual, 8th edition). Participants must have resectable disease
• Participants in Cohorts 1, 2, 3B, 4 and 5 must have measurable disease according to RECIST version 1.1. Participants in Cohort 3A and Cohort 6 must have evaluable disease (defined as having at least 1 non-target lesion according to RECIST version 1.1.
• Cohorts 1, 2, 3A, 3B, 4, and 5 only: 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)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 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 within 7 days prior to the date of the laboratory test.

Participants should have: a) Hemoglobin >=9 grams per deciliter (g/dL); b) Neutrophils >=1.5 x 10^3/mcg; c) Platelets >=100 x 10^3/mcg

Exclusion criteria

• 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
• Participant with untreated brain metastases leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation
• Participant with a history of clinically significant cardiovascular disease
• 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
• Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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287 participants in 7 patient groups

Cohort 1: Amivantamab Monotherapy (Dose Expansion)

Experimental group

Description:

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.

Treatment:

Biological: Amivantamab

Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in)

Experimental group

Description:

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 (IV) injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle).

Treatment:

Biological: Pembrolizumab

Biological: Amivantamab

Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Biological: Amivantamab

Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Biological: Amivantamab

Cohort 4: Amivantamab Monotherapy

Experimental group

Description:

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.

Treatment:

Biological: Amivantamab

Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion)

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab

Drug: Carboplatin

Biological: Amivantamab

Cohort 6: Amivantamab + Pembrolizumab

Experimental group

Description:

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, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle) (Neoadjuvant Phase). In the adjuvant phase, pembrolizumab IV (200 mg) will be administered q3w from Adjuvant Cycle 1 Day 1 to Adjuvant Cycle 15 Day 1 and amivantamab SC 2,400 mg (3,360 mg for \>80 kg) will be administered q3w from Adjuvant Cycle 4 Day 1 to Adjuvant Cycle 15 Day 1.

Treatment:

Biological: Pembrolizumab

Biological: Amivantamab