The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumours with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with non-small cell lung cancer with a specific mutation in the HER2 gene. The purpose of the first study part is to find the highest dose of a medicine called zongertinib the participants can tolerate. Once this dose is found, it will be used in the second study part to test whether zongertinib can make tumours shrink. In this study, zongertinib is given to people for the first time. Participants take zongertinib as tablets once a day or twice a day. The participants are in the study for as long as they benefit from and can tolerate treatment. Study doctors regularly check the participants' health and monitor the tumours. The doctors also take note of any unwanted effects that could have been caused by zongertinib.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
554
zongertinib
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGPrecision NextGen Oncology
Beverly Hills, California, United States
NOT_YET_RECRUITINGCity of Hope-Duarte-56419
Duarte, California, United States
RECRUITINGCity of Hope - Seacliff
Huntington Beach, California, United States
Phase Ia: Maximum Tolerated Dose (MTD)
Maximum tolerated dose is defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal to or above 33% during the MTD evaluation period in any studied regimen.
Time frame: At the end of Cycle 1 (each cycle is 21 days).
Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) in the MTD evaluation period
Time frame: At the end of Cycle 1 (each cycle is 21 days).
Phase Ib - Cohorts 1, 2 and 5 : Objective response (OR) as assessed by central independent review
OR is defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, from the first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 3, 6, 7, and 8: Objective response according to RECIST 1.1 by investigator assessment
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib: Cohort 4: Objective response according to Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM) by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ia: Number of patients experiencing DLTs during the entire treatment period
Time frame: From the start of the trial treatment until end of month 8, up to 8 months.
Phase Ia: Maximum measured concentration of zongertinib in plasma (Cmax)
Time frame: On day 1 and on day 15 of Cycle 1 (each cycle is 21 days).
Phase Ia: Area under the concentration-time curve of zongertinib in plasma (AUC0-t2)
Time frame: On day 1 and on day 15 of Cycle 1 (each cycle is 21 days).
Phase Ib - Cohorts 1, 2 and 5: Duration of objective response (DoR) according to RECIST 1.1
DoR is defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response as assessed by central independent review.
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Disease control (DC)
DC is defined as best overall response of complete response (CR) or partial response (PR) or stable disease (SD) where best overall response is defined according to RECIST version 1.1 as assessed central independent review, from first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent.
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Progression-free survival (PFS)
PFS is defined as the time from first treatment administration until tumor progression according to RECIST version 1.1 as assessed by central independent review, or death from any cause, whichever occurs earlier.
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Objective response according to response assessment in neuro-oncology for brain metastases (RANO-BM) criteria as assessed by central independent review for patients with central nervous system (CNS) lesions at baseline
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Disease control according to RANO-BM criteria as assessed by central independent review for patients with CNS lesions at baseline
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Objective response according to RECIST 1.1 criteria as assessed by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 1, 2 and 5: Disease control according to RECIST 1.1 criteria as assessed by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 3, 6, 7 and 8: Duration of objective response according to RECIST 1.1 by investigator assessment
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 3, 6, 7 and 8: Disease control according to RECIST 1.1 as assessed by the investigator
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 3, 6, 7 and 8: Progression-free survival according to RECIST 1.1 as assessed by the investigator
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 3, 6, 7 and 8: Objective response according to RANO-BM criteria as assessed by the investigator for patients with CNS lesions at baseline
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohorts 3, 6, 7 and 8: Disease control according to RANO-BM criteria as assessed by the investigator for patients with CNS lesions at baseline
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Duration of objective response (DoR) according to RANO-BM by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Disease control (DC) according to RANO-BM by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Progression-free survival (PFS) according to RANO-BM as assessed by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: DoR according to RECIST 1.1 by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: DC according to RECIST 1.1 by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: PFS according to RECIST 1.1 as assessed by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: OR according to RECIST 1.1 by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: Duration of OR according to RECIST 1.1 by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - Cohort 4: PFS according to RECIST 1.1 by central independent review
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - All cohorts: Overall survival (OS), defined as time from first treatment administration until death from any cause
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - All Cohorts: Number of patients experiencing DLTs during the entire treatment period
Time frame: From the start of the trial treatment until end of month 12, up to 12 months.
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) physical functioning domain score
Time frame: Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score
Time frame: Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
Phase Ib - All Cohorts: Change from baseline to Day 1 of Cycle 5 in EORTC item List 46 (IL46) score
Time frame: Baseline and on Day 1 of Cycle 5 (each cycle is 21 days).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
City of Hope-Irvine-69674
Irvine, California, United States
NOT_YET_RECRUITINGValkyrie Clinical Trials
Los Angeles, California, United States
RECRUITINGUniversity of California Irvine
Orange, California, United States
RECRUITINGUniversity of California Davis
Sacramento, California, United States
RECRUITINGGeorgetown University
Washington D.C., District of Columbia, United States
RECRUITINGHoly Cross Hospital-Fort Lauderdale-57892
Fort Lauderdale, Florida, United States
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