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 (130)
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Horizon Ridge Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Southeast Henderson - Stephanie
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II
🇺🇸Las Vegas, Nevada, United States
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
The Toledo Clinic Cancer Center
🇺🇸Toledo, Ohio, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Scroll for more (120 remaining)Comprehensive Cancer Centers of Nevada - Henderson🇺🇸Henderson, Nevada, United StatesRamalingam RatnasabapathyPrincipal Investigator