REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors)
- Conditions
- Advanced or Metastatic NSCLS With Exon 20 Insertion Mutation
- Interventions
- Registration Number
- NCT05973773
- Lead Sponsor
- Taiho Oncology, Inc.
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of zipalertinib in combination with standard first-line platinum-based chemotherapy compared to chemotherapy alone, in patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations.
- Detailed Description
This study will evaluate the efficacy and safety of zipalertinib in combination with standard chemotherapy with pemetrexed and a platinum agent (either carboplatin or cisplatin) in patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC harboring EGFR ex20ins mutations.
The study will be conducted in two parts:
* Part A: Safety lead-in to determine the recommended dose of zipalertinib in combination with standard chemotherapy pemetrexed and a platinum agent (either carboplatin or cisplatin) to be studied in Part B of the study.
* Part B: Randomized, controlled, open-label, multinational Phase 3 study to assess the efficacy and safety of zipalertinib in combination with standard chemotherapy with pemetrexed and a platinum agent (either carboplatin or cisplatin) compared to standard chemotherapy alone. Patients randomized to the chemotherapy-only treatment arm in Part B may receive treatment with zipalertinib as monotherapy after BICR-assessed progressive disease (PD) is documented (optional "crossover arm").
An independent data monitoring committee (IDMC) will be established to monitor interim safety Data.
A treatment cycle is defined as 21 days for both parts of the study.
Part A: Safety Lead-In The primary objective of Part A is to determine the recommended dose of zipalertinib administered in combination with pemetrexed and a platinum agent (either carboplatin or cisplatin) to be studied in the Phase 3 portion of this study.
Approximately 6-12 patients will receive zipalertinib administered at an initial dose of zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or cisplatin on a 21-day cycle. Patients may continue to receive study treatment until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first. Patients will be enrolled using a rolling-6 design,35 and the determination of the dose of zipalertinib to be used in Part B of the study will be informed by the incidence of dose-limiting toxicities (DLTs) observed during Cycle 1.
Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following completion of Part A.
Approximately 260 patients will be randomized on a 1:1 basis to receive pemetrexed and a platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day cycle.
Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of PD or until other withdrawal criteria are met, whichever comes first.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 272
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A (Safety Lead in) TAS6417 Part A: Safety Lead-In Approximately 6-12 patients will receive zipalertinib administered at an initial dose of zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or cisplatin on a 21-day cycle. Patients may continue to receive study treatment until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first. Part B TAS6417 Enrollment into the Phase 3 portion of the study will begin following completion of Part A. Approximately 260 patients will be randomized on a 1:1 basis to receive pemetrexed and a platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day cycle. Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of PD or until other withdrawal criteria are met, whichever comes first.
- Primary Outcome Measures
Name Time Method Part A and Part B: Progression-free survival (PFS) by blinded independent central review (BICR) approximately 5 years Part A and B: The rate and severity of treatment emergent AEs approximately 5 years Part A: The rate and severity of DLTs according to the NCI-Common Terminology Criteria of Adverse Events (CTCAE) v5.0 during Cycle 1 approximately 5 years
- Secondary Outcome Measures
Name Time Method Part A and Part B: Intracranial duration of complete response (iDCR) approximately 5 years Part A and Part B: Objective response rate (ORR) approximately 5 years Part A and Part B: Duration of response (DoR) approximately 5 years Part A and Part B: Intracranial (i) Overall Response Rate (iORR) approximately 5 years Part A and Part B: Intracranial duration of Response (iDoR) approximately 5 years Part B: Overall survival (OS) approximately 5 years Part A and Part B: Disease control rate (DCR) approximately 5 years European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 approximately 5 years The EORTC QLQ-C30 is a "core questionnaire" which incorporates a range of physical, emotional and social health developed to assess the quality of life of cancer patients. This scale is numbered from 30 to 130. The higher the score equates to better functioning.
Non-small Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ ) approximately 5 years The NSCLC- SAQ was developed to incorporate the patient's perspective into evaluation of clinical benefit in advanced non-small cell lung cancer trials.. Qualitative evidence supports 7 items covering 5 symptom concepts with the total score measuring overall severity of the following NSCLC symptoms: cough, pain, dyspnea, fatigue, and appetite. Lower scores indicate lower symptom severity.
Pharmacokinetic (PK) parameter approximately 5 years Minimum observed concentration (Cmin)
European Quality of Life 5 Dimensions, 3 Level Version (EQ-5D-3L) approximately 5 years The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. This scale is numbered from 0 to 100. The higher the score the better the outcome
Trial Locations
- Locations (114)
Clínica Neoplasias Litoral
🇧🇷Itajaí, Santa Catatina, Brazil
Trakya Üniversitesi Sa?l?k Ara?t?rma ve Uygulama Merkezi
🇹🇷Edirne, Turkey
Ankara Il Saglik Mudurlugu SBU Gulhane Egitim Ve Arastirma Hastanesi
🇹🇷Etlik, Turkey
Bagcilar Medipol Mega Universite Hastanesi
🇹🇷Istanbul, Turkey
Gustave Roussy
🇫🇷Villejuif, Val-de-Marne, France
Clinica SIGMedical
🇷🇴Suceava, Romania
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
Clínica Integral Internacional de Oncología S de RL de CV
🇲🇽Mirador, Puebla, Mexico
Centrul de Oncologie Sf Nectarie
🇷🇴Craiova, Dolj, Romania
Oncocare Cancer Centre
🇸🇬Singapore, Singapore
FAICIC Clínical Research
🇲🇽Veracruz, Mexico
Comprehensive Cancer Centers of Nevada - Southwest
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley - Twain
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
Gabrail Cancer and Research Center
🇺🇸Canton, Ohio, United States
Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Ceará, Brazil
Asian Hospital and Medical Center
🇵🇭Muntinlupa, Philippines
Medisprof
🇷🇴Cluj-Napoca, Cluj, Romania
Oncocenter - Oncologie Clinica
🇷🇴Timişoara, Timis, Romania
Icon Cancer Centre Mount Elizabeth
🇸🇬Singapore, Singapore
Comprehensive Cancer Centers of Nevada - Horizon Ridge Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Southeast Henderson - Stephanie
🇺🇸Henderson, Nevada, United States
Algemeen Ziekenhuis Maria Middelares
🇧🇪Gent, Oost-Vlaaderen, Belgium
Algemeen Ziekenhuis Delta - Campus Menen
🇧🇪Menen, West Flanders, Belgium
Algemeen Ziekenhuis Delta - Campus Rumbeke
🇧🇪Rosières, West-Vlaanderen, Belgium
Icon Cancer Centre - Mount Alvernia
🇸🇬Singapore, Singapore
Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II
🇺🇸Las Vegas, Nevada, United States
The Toledo Clinic Cancer Center
🇺🇸Toledo, Ohio, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
🇧🇪Leuven, Flemish Brabant, Belgium
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Amaral Carvalho
🇧🇷Jaú, São Paulo, Brazil
Multi-profile Hospital for Active Treatment Uni Hospital
🇧🇬Panagyurishte, Pazardzhik, Bulgaria
University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna-ISUL
🇧🇬Sofia, Bulgaria
William Osler Health System - Brampton Civic Hospital
🇨🇦Brampton, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Les Hôpitaux Universitaires de Strasbourg
🇫🇷Strasbourg cedex, Alsace, France
Hôpital Côte De Nacre
🇫🇷Caen cedex 9, Basse-Normandie, France
Institut Curie
🇫🇷Paris cedex, Ile-de-France, France
Centre Hospitalier Universitaire Limoges
🇫🇷Limoges, Limousin, France
Hôpital Haut-Lévêque
🇫🇷Pessac, Nouvelle-Aquitaine, France
Centre Hospitalier Le Mans
🇫🇷Le Mans cedex 9, Pays De La Loire, France
Hôpital Ambroise-Paré
🇫🇷Boulogne-Billancourt, Île-de-France, France
Asklepios Klinik Altona
🇩🇪Hamburg, Hamburg (Hansestadt), Germany
Universitätsklinikum Gießen und Marburg - Gießen
🇩🇪Gießen, Hessen, Germany
LMU Klinikum - Campus Innenstadt
🇩🇪München, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
General Hospital for Thoracic Diseases Sotiria
🇬🇷Athens, Attica, Greece
Metropolitan General
🇬🇷Piraeus, Attica, Greece
University General Hospital of Patras
🇬🇷Patra, Peloponnese, Greece
Metropolitan Hospital
🇬🇷Peiraias, Pireas, Greece
University General Hospital of Larissa
🇬🇷Larissa, Thessaly, Greece
BioClinic Thessaloniki
🇬🇷Thessaloniki, Greece
Emek Medical Center
🇮🇱Afula, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Hadassah University Hospital Ein Kerem
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Assuta Hospital - Ramat HaHayal
🇮🇱Tel aviv, Israel
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
🇮🇹Meldola, Forlì-Cesena, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
🇮🇹Milan, Italy
Azienda Ospedaliero - Universitaria di Modena
🇮🇹Modena, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Azienda Unità Sanitaria Locale della Romagna
🇮🇹Ravenna, Italy
Azienda Ospedaliera Universitaria Integrata Verona
🇮🇹Verona, Italy
Aichi Cancer Center
🇯🇵Nagoya, Aiti [Aichi], Japan
Hirosaki University Hospital
🇯🇵Hirosaki-Shi, Aomori, Japan
Kyushu Cancer Center
🇯🇵Fukuoka-shi, Hukuoka, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Kanagawa, Japan
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Yokohama, Kanagawa, Japan
Saiseikai Kumamoto Hospital
🇯🇵Kumamoto-Shi, Kumamoto, Japan
Sendai Kousei Hospital
🇯🇵Sendai, Miyagi, Japan
Okayama University Hospital
🇯🇵Okayamashi, Okayama, Japan
Kansai Medical University Hospital
🇯🇵Hirakata, Osaka, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
🇯🇵Sakai-Shi, Osaka, Japan
Cancer Institute Hospital of JFCR
🇯🇵Koto, Tokyo, Japan
Keio University Hospital
🇯🇵Shinjuku-Ku, Tokyo, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
Osaka City General Hospital
🇯🇵Osaka, Japan
Osaka Prefectural Hospital Organization - Osaka International Cancer Institute
🇯🇵Osaka, Japan
Catholic University of Korea Saint Vincent's Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Gyeongsang National University Hospital
🇰🇷Jinju, Gyeongsangnamdo [Kyongsangnam-do], Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Incheon Gwang'yeogsi [Inch'on-Kwangyokshi], Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Gelderland, Netherlands
Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Noord-Holland, Netherlands
St. Luke's Medical Center - Quezon City
🇵🇭Quezon City, Metropolitan Manila, Philippines
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
🇵🇱Lublin, Lubelskie, Poland
Instytut MSF
🇵🇱Łódź, Lódzkie, Poland
Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandów
🇵🇱Pozna?, Wielkopolskie, Poland
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, La Coruña, Spain
Clínica Mi Tres Torres
🇪🇸Barcelona, Spain
Hospital Quirónsalud Barcelona
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de Jaén
🇪🇸Jaén, Spain
MD Anderson Cancer Center Madrid
🇪🇸Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Regional Universitario de Málaga - Hospital General
🇪🇸Málaga, Spain
Faculty of Medicine Siriraj Hospital
🇹🇭Bang Phlat, Bangkok, Thailand
King Chulalongkorn Memorial Hospital
🇹🇭Pathum Wan, Bangkok, Thailand
Navamindradhiraj University - Faculty of Medicine Vajira Hospital
🇹🇭Krung Thep Maha Nakhon, Khet Dusit, Thailand
T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastanesi
🇹🇷Adana, Turkey
Medical Park Seyhan Hastanesi
🇹🇷Adana, Turkey
Hacettepe Üniversitesi Kanser Enstitüsü
🇹🇷Ankara, Turkey
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
T.C. Saglik Bakanligi - Istanbul Il Saglik Mudurlugu - Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
🇹🇷Istanbul, Turkey
Royal Free London NHS Foundation Trust
🇬🇧London, England, United Kingdom
T.C. Saglik Bakanligi Ankara Bilkent Sehi?r Hastanesi?
🇹🇷Çankaya, Turkey
Torbay and South Devon NHS Foundation Trust
🇬🇧Torquay, England, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, England, United Kingdom