This study is open to adults with advanced cancer (solid tumors) and people with advanced head and neck cancer. The study has 2 parts. The purpose of Part 1 of this study is to find the highest dose of a medicine called BI 765179 that people with solid tumors can tolerate when taken alone or together with a medicine called ezabenlimab. The goal of Part 2 is to find out whether BI 765179 in combination with a medicine called pembrolizumab helps people with advanced head and neck cancer. In Part 1, each participant is put into 1 of 2 groups. Participants get BI 765179 alone or in combination with ezabenlimab as infusion into a vein every 3 weeks. In Part 2, participants are also divided into 2 groups. 1 group gets a low dose of BI 765179 in combination with pembrolizumab and the other group gets a high dose of BI 765179 in combination with pembrolizumab. Participants receive the study treatment as infusions into a vein. BI 765179, ezabenlimab, and pembrolizumab are antibodies that may help the immune system fight cancer. In this study, BI 765179 is given to people for the first time. Participants can stay in the study up to 2 years if they benefit from treatment and can tolerate it. The doctors regularly check the participants' health and note any health problems that could have been caused by the study treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
151
University of Arizona
Tucson, Arizona, United States
Beverly Hills Cancer Center
Beverly Hills, California, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Avera Cancer Institute
Sioux Falls, South Dakota, United States
NEXT Oncology-San Antonio-65273
San Antonio, Texas, United States
Phase 1a: Maximum Tolerated Dose (MTD)
MTD 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. The MTD will be assessed based on the number of patients experiencing DLTs, graded according to Common terminology criteria for adverse events (CTCAE) version 5.0, during the MTD evaluation period.
Time frame: Up to Day 21 (end of Cycle 1)
Phase 1a: Occurrence of Dose Limiting Toxicities (DLTs) in the MTD evaluation period
Time frame: Up to Day 21 (end of Cycle 1)
Phase 1b: Objective response (OR)
OR is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response evaluation criteria in solid tumors (RECIST) version (v) 1.1 by Investigator assessment from the date of treatment start until the earliest date 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: Up to 2 years.
Phase 1a: Occurrence of DLTs during the on-treatment period (per arm)
Time frame: up to 36 months
Phase 1a: Maximum measured concentration of BI 765179 in plasma (Cmax)
Time frame: Up to Day 21 (end of Cycle 1)
Phase 1a: Area under the concentration-time curve of BI 765179 in plasma over a uniform dosing interval from zero to 504h (AUC0-504)
Time frame: Up to Day 21 (end of Cycle 1)
Phase Ib: Occurrence of adverse events (AEs) using the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5
Time frame: Up to 2 years.
Phase 1b: Occurrence of serious AEs (SAEs) during the on-treatment period
Time frame: Up to 2 years.
Phase 1b: OR assessed by the Investigator according to immune-related RECIST (iRECIST)
OR assessed by the Investigator according to immuno-related RECIST (iRECIST) is defined as best overall response of immune-related complete response (iCR) and immune related partial response (iPR), where the best overall response is the best time point response recorded from the first administration of study medication until the end of treatment.
Time frame: Up to 2 years.
Phase Ib: Duration of response (DoR) assessed by RECIST v1.1
DoR assessed by RECIST v1.1 is defined as the time from first documented CR or PR until the earliest of PD or death among patients with an OR.
Time frame: Up to 2 years.
Phase 1b: DoR assessed by iRECIST
DoR assessed by iRECIST is defined as the time from first documented iCR or iPR until the earliest of unconfirmed progression of disease (iUPD) or death among patients with an OR (iCR, iPR).
Time frame: Up to 2 years.
Phase 1b: Progression-free survival (PFS) in all patients assessed by the Investigator according to RECIST v1.1
PFS in all patients assessed by the Investigator according to RECIST v1.1 is defined as the time from first treatment administration until tumor progression or death from any cause, whichever occurs earlier.
Time frame: Up to 2 years.
Phase 1b: PFS in all patients assessed by the Investigator according to iRECIST
PFS in all patients assessed by the Investigator according to iRECIST is defined as the time from first administration of study medication until the first date of iUPD (provided that confirmed progressive disease (iCPD) is the next time point response, i.e., progression is confirmed at the next tumor assessment) or death from any cause, whichever occurs earlier.
Time frame: Up to 2 years.
Phase 1b: PFS rate at 14 weeks
PFS rate at 14 weeks is defined as the proportion of patients who survive and are progression free at least 14 weeks after the date of first treatment.
Time frame: Up to 2 years.
Phase 1b: Overall survival (OS)
OS is defined as the time from first treatment administration until death from any cause.
Time frame: Up to 2 years.
Phase 1b: OS rate at 12 months
OS rate at 12 months is defined as the proportion of patients with OS ≥12 months after the date of first treatment.
Time frame: Up to 2 years.
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