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

Официальное название

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

Обзор

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).

Вмешательства

• Биопрепарат Amivantamab
  Amivantamab will be administered subcutaneously.
• Биопрепарат Pembrolizumab
  Pembrolizumab will be administered intravenously.
• Препарат Paclitaxel
  Paclitaxel will be administered intravenously.
• Препарат Carboplatin
  Carboplatin will be administered intravenously.

Первичные конечные точки

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

Вторичные конечные точки (12)

• Cohorts 1, 2, 3B, 4 and 5: Duration of Response (DoR) [Срок оценки: 2 years and 2 months]
• Cohorts 1, 2, 3B, 4 and 5: Clinical Benefit Rate (CBR) [Срок оценки: 2 years and 2 months]
• Cohorts 1, 2, 3B, 4 and 5: Progression-free Survival (PFS) [Срок оценки: 2 years and 2 months]
• Cohorts 1, 2, 3B, 4, 5 and 6: Overall Survival (OS) [Срок оценки: 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 [Срок оценки: 2 years and 1 month]
• Cohort 1 and 4: Maximum Observed Serum Concentration (Cmax) of Amivantamab [Срок оценки: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Time to Maximum Observed Serum Concentration (Tmax) of Amivantamab [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Trough Serum Concentration (Ctrough) of Amivantamab [Срок оценки: Predose up to 168 hours post dose on Day 1]
• Cohort 1 and 4: Accumulation Ratio (R) of Amivantamab [Срок оценки: Predose up to 168 hours post dose on Day 1]
• Cohort 6: Event-Free Survival (EFS) [Срок оценки: 2 years and 2 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 15 центров

• 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
• … и ещё 7 центров

Великобритания · 7 центров

• 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

Китай · 6 центров

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

Франция · 5 центров

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

Тайвань · 5 центров

• 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 центра

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

Испания · 4 центра

• 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

Германия · 3 центра

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

Польша · 3 центра

• 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

Япония · 2 центра

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

Малайзия · 2 центра

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

Публикации

• 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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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