A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer

Official title

A Phase 1b/2, Open-label Study of Amivantamab Monotherapy and Amivantamab in Addition to Other Therapeutic Agents in Participants With Head and Neck Squamous Cell Carcinoma

Overview

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).

Interventions

• Biological Amivantamab
  Amivantamab will be administered subcutaneously.
• Biological Pembrolizumab
  Pembrolizumab will be administered intravenously.
• Drug Paclitaxel
  Paclitaxel will be administered intravenously.
• Drug Carboplatin
  Carboplatin will be administered intravenously.

Primary outcome measures

• Cohorts 1, 2, 3B, 4 and 5: Objective Response Rate [Time frame: 2 years and 2 months]
• Cohort 3A: Number of Participants With Dose-limiting Toxicities (DLT) [Time frame: Up to 21 days]
• Cohort 3A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Severity [Time frame: 2 years and 1 month]
• Cohort 6: Major Pathologic Response (MPR) [Time frame: 2 years and 2 months]

Secondary outcome measures (12)

• Cohorts 1, 2, 3B, 4 and 5: Duration of Response (DoR) [Time frame: 2 years and 2 months]
• Cohorts 1, 2, 3B, 4 and 5: Clinical Benefit Rate (CBR) [Time frame: 2 years and 2 months]
• Cohorts 1, 2, 3B, 4 and 5: Progression-free Survival (PFS) [Time frame: 2 years and 2 months]
• Cohorts 1, 2, 3B, 4, 5 and 6: Overall Survival (OS) [Time frame: 2 years and 2 months]
• Cohorts 1, 2, 3B, 4, 5 and 6: Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Severity [Time frame: 2 years and 1 month]
• Cohort 1 and 4: Maximum Observed Serum Concentration (Cmax) of Amivantamab [Time frame: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Time to Maximum Observed Serum Concentration (Tmax) of Amivantamab [Time frame: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Area Under the Serum Concentration Curve Verses Time Curve From Time t1 to t2 (AUC[t1-t2]) of Amivantamab [Time frame: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Area Under the Curve From Time Zero to tau (AUC[0-tau]) of Amivantamab [Time frame: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Trough Serum Concentration (Ctrough) of Amivantamab [Time frame: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Accumulation Ratio (R) of Amivantamab [Time frame: Predose up to 168 hours post dose on Day 1]
• Cohort 6: Event-Free Survival (EFS) [Time frame: 2 years and 2 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• University of California at San Diego Moores Cancer Center — La Jolla
• University of Colorado Denver Anschultz Medical Campus — Aurora
• Yale Cancer Center — New Haven
• The University of Chicago Medical Center (UCMC) — Chicago
• University of Maryland School of Medicine — Baltimore
• Dana Farber Cancer Institute — Boston
• University of Michigan Rogel Cancer Center — Ann Arbor
• Karmanos Cancer Institute — Detroit
• … and 7 more centers

United Kingdom · 7 centers

• Addenbrooke's Hospital — Cambridge
• The Royal Surrey County Hospital NHS Foundation Trust — Guildford
• Royal Marsden Hospital (Sutton) — London
• Royal Marsden Hospital — London
• Imperial College London and Imperial College Healthcare NHS Trust — London
• University College London Hospitals — London
• The Christie Nhs Foundation Trust — Manchester

China · 6 centers

• Beijing Cancer Hospital of Peking University — Beijing
• West China School of Medicine/West China Hospital, Sichuan University — Cheng Du Shi
• Linyi Cancer Hospital — Linyi
• Fudan Cancer Hospital — Shanghai
• Shanghai East Hospital — Shanghai
• Union Hospital Tongji Medical College of Huazhong University of Science and Technology — Wuhan

France · 5 centers

• Institut Sainte Catherine — Avignon
• Centre Oscar Lambret — Lille
• CHU Nantes — Nantes
• Institut Curie — Paris
• Gustave Roussy — Villejuif

Taiwan · 5 centers

• Changhua Christian Hospital — Changhua
• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City
• National Taiwan University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei
• Linkou Chang Gung Memorial Hospital — Taoyuan

South Korea · 4 centers

• Seoul National University Hospital — Seoul
• Severance Hospital Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Spain · 4 centers

• Hosp Univ Vall D Hebron — Barcelona
• Inst. Cat. Doncologia-H Duran I Reynals — Barcelona
• Hosp. Univ. Ramon Y Cajal — Madrid
• Hosp. Univ. 12 de Octubre — Madrid

Germany · 3 centers

• Universitaetsklinikum Essen — Essen
• Universitaetsklinikum Leipzig — Leipzig
• Klinikum der Landeshauptstadt Stuttgart — Stuttgart

Poland · 3 centers

• Uniwersyteckie Centrum Kliniczne — Gdansk
• Centrum Onkologii Instytut im M Sklodowskiej Curie Oddzial w Gliwicach — Gliwice
• Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy — Warsaw

Japan · 2 centers

• Aichi Cancer Center — Nagoya
• Tokyo Medical University Hospital — Tokyo

Malaysia · 2 centers

• Pantai Hospital Kuala Lumpur — Kuala Lumpur
• University Malaya Medical Centre — Kuala Lumpur

Publications

• Burtness B, Rosenberg AJ, Calderon B, Lim SM, Yang MH, Li SH, Kadowaki S, Swiecicki PL, Geiger JL, Ince W, Hahn D, Guo Y, Adkins D, Metcalf R, Ahn MJ, Sukari A, Brana I, Keam B, Tanaka H, Sheth S, Oliva M, Lyu X, Curtin JC, Toyoizumi K, Xie J, Wade M, Diorio B, Kapoor A, Yilmaz E, Baig M, Kim P, Verheijen RB, Shah S, Harrington KJ; OrigAMI-4 Cohort 1 Investigators. Amivantamab in Recurrent/Metasta PMID 42218660

Identifiers

NCT: NCT06385080 · 61186372HNC2002 · 61186372HNC2002 · 2023-508418-40-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗