An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics, and Tumor Response Profile of the Diacylglycerol Kinase Zeta Inhibitor (DGKzi) BAY 2965501 as Monotherapy, and in Combination, in Participants With Advanced Solid Tumors
Condition: Advanced Solid Tumors
Study Type: Interventional
Clinical Trials Identifier NCT 8-digits: NCT05614102
Sponsor: Bayer
Phase: Phase 1
Eligibility:
- Age: minimum 18 Years maximum N/A
- Gender: All
Inclusion Criteria:
- Have measurable disease per Response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) as assessed by the local site investigator.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Participants with histologically confirmed diagnosis of a solid tumor (specifications for the different parts of the study below) will be enrolled onto this study: • Dose escalation: All solid cancers, except primary central nervous system cancers
- The following tumor types will be recruited to the monotherapy expansion cohorts:
- Non-small cell lung cancer (NSCLC)
- Gastric/Gastroesophageal Junction (GEJ) adenocarcinoma
- The following tumor types will be recruited to the BAY 2965501 and pembrolizumab combination expansion cohorts:
- NSCLC: participants with tumors that are TPS score ≥50% PDL-1 high (based on local historical testing) and are eligible for standard of care anti-PD(L)-1 monotherapy in the first line incurable treatment setting.
- NSCLC
- Gastric/GEJ adenocarcinoma
Exclusion Criteria:
- Previous therapy with a DGK inhibitor is prohibited for monotherapy cohorts (participants previously treated with BAY 2965501 or BAY 2862789 must have progressed on that DGK inhibitor (and not discontinued for toxicity) to be eligible for combination).
- Has received a prior therapeutic regimen containing an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or an agent directed to another co-stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher infusion-related adverse event (irAE).
- Participants with new brain metastases on screening brain MRI/CT. Previously treated brain metastases that are progressive at screening compared to a brain MRI/CT at least 6 weeks earlier are also excluded. Participants with known previously treated brain metastases, which are radiologically stable compared to a CT/MRI scan at least 6 weeks earlier, clinically stable and without the requirement of steroid treatment for at least 14 days prior to the first dose of study treatment may be eligible.
- Primary central nervous system malignancy or presence of leptomeningeal disease (i.e., positive cerebrospinal fluid cytology or unequivocal radiological or clinical evidence of leptomeningeal involvement).
- Participants with gastrointestinal conditions that may compromise oral absorption such as short bowel syndrome or active tumor-related bowel obstruction with ongoing symptoms compromising absorption over last 6 months.
View trial on ClinicalTrials.gov