An Open Label, Phase I Dose-finding and Expansion Study of BI 765179 as Monotherapy and in Combination With Ezabenlimab (BI 754091) in Patients With Advanced Solid Cancers, and BI 765179 in Combination With Pembrolizumab in First-line PD-L1-positive Metastatic or Incurable, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)
Overview
- Phase
- Phase 1
- Intervention
- BI 765179
- Conditions
- Not specified
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 151
- Locations
- 82
- Primary Endpoint
- Phase 1a: Maximum Tolerated Dose (MTD)
- Status
- Active, not recruiting
- Last Updated
- 4 days ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All cohorts:
- •Patients with locally advanced, unresectable or metastatic solid tumors who are either refractory after standard therapy for the disease or for whom standard therapy is not appropriate
- •Tumor with expected high expression of Fibroblast activation protein (FAP) of the following histologies:
- •Non-small cell lung carcinoma (NSCLC)
- •Gastric cancer
- •Esophageal adenocarcinoma or squamous cell carcinoma
- •Urothelial bladder carcinoma
- •Head and neck squamous cell carcinoma
- •Cutaneous malignant melanoma
- •Cutaneous squamous cell carcinoma
Exclusion Criteria
- •Currently enrolled in another investigational device or drug trial
- •Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except:
- •Effectively treated non-melanoma skin cancers
- •Effectively treated carcinoma in situ of the cervix
- •Effectively treated ductal carcinoma in situ
- •Other effectively treated malignancy that is considered cured by 'local treatment'
- •Previous treatment with agents targeting CD137
- •Known leptomeningeal disease or spinal cord compression due to disease
- •Anticoagulant treatment that cannot be safely interrupted if medically needed (e.g., biopsy) based on the opinion of the Investigator
- •Persistent toxicity from previous treatments that has not resolved to ≤ Common terminology criteria for adverse events (CTCAE) Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy)
Arms & Interventions
Phase 1 Arm A: BI 765179
Intervention: BI 765179
Phase 1a Arm B: BI 765179 + ezabenlimab
Intervention: BI 765179
Phase 1a Arm B: BI 765179 + ezabenlimab
Intervention: Ezabenlimab
Phase 1b Cohort 1: pembrolizumab + low dose of BI 765179
Intervention: Pembrolizumab
Phase 1b Cohort 2: pembrolizumab + high dose of BI 765179
Intervention: Pembrolizumab
Phase 1b Cohort 2: pembrolizumab + high dose of BI 765179
Intervention: BI 765179
Phase 1b Cohort 1: pembrolizumab + low dose of BI 765179
Intervention: BI 765179
Outcomes
Primary Outcomes
Phase 1a: Maximum Tolerated Dose (MTD)
Time Frame: Up to Day 21 (end of Cycle 1)
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.
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)
Time Frame: Up to 2 years.
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.
Secondary Outcomes
- Phase 1a: Occurrence of DLTs during the on-treatment period (per arm)(up to 36 months)
- Phase 1a: Maximum measured concentration of BI 765179 in plasma (Cmax)(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)(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(Up to 2 years.)
- Phase 1b: Occurrence of serious AEs (SAEs) during the on-treatment period(Up to 2 years.)
- Phase 1b: OR assessed by the Investigator according to immune-related RECIST (iRECIST)(Up to 2 years.)
- Phase Ib: Duration of response (DoR) assessed by RECIST v1.1(Up to 2 years.)
- Phase 1b: DoR assessed by iRECIST(Up to 2 years.)
- Phase 1b: Progression-free survival (PFS) in all patients assessed by the Investigator according to RECIST v1.1(Up to 2 years.)
- Phase 1b: PFS in all patients assessed by the Investigator according to iRECIST(Up to 2 years.)
- Phase 1b: PFS rate at 14 weeks(Up to 2 years.)
- Phase 1b: Overall survival (OS)(Up to 2 years.)
- Phase 1b: OS rate at 12 months(Up to 2 years.)