An Open-label, Phase I, 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 in Participants With Advanced Solid Tumors
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Study Summary
The main purpose of this first-in-human study is to learn:
how safe different doses of BAY2965501 are, the degree to which medical problems caused by BAY2965501 can be tolerated (also called tolerability),
what maximum amount can be given, and how it moves into, through and out of the body.
The study will have two parts.
The first part, called dose escalation, is done to find the most appropriate dose that can be given in the second part. For this, each participant will receive one of the increasing doses of BAY2965501. They will take BAY2965501 daily by mouth.
All participants in the second part, called dose expansion, will receive the most appropriate dose from the first part daily as tablet by mouth.
To evaluate the safety, tolerability, maximum tolerated or administered dose, pharmacokinetics, pharmacodynamics, and tumor response profile of BAY 2965501.
To evaluate the safety and resistance of the drug alone or in combination with anti-PD-1 monoclonal antibodies in the treatment of advanced solid tumors.
To evaluate the safety, tolerability, maximum tolerated dose or maximum administered dose, pharmacokinetics, pharmacodynamics, and tumor response of the diacylglycerol kinase zeta inhibitor (DGKzi) BAY 2965501 as monotherapy and in combination therapy in study participants with advanced solid tumors
- 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 (for monotherapy or BAY 2965501 and pembrolizumab combination cohorts): All solid cancers, except primary central nervous system cancers •Dose escalation (for BAY 2965501 with pembrolizumab and platinum-based regimen combination cohorts): All solid cancers, except primary central nervous system cancers, (including Non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), cervical, endometrial, triple negative breast cancer) that are eligible for standard of care platinum-based regimen and for whom this trial is a reasonable option for them.
- The following tumor types may be recruited to the monotherapy expansion cohorts:
- o Non-small cell lung cancer (NSCLC)
- The following tumor types may be recruited to the BAY 2965501 and pembrolizumab combination expansion cohorts:
- NSCLC: participants who are treatment-naïve in the incurable disease setting.
- NSCLC: Participants with metastatic NSCLC (confirmed histologically or cytologically)
- Gastric/GEJ adenocarcinoma
- other tumor types may be explored based on emerging data
- The following tumor types will be recruited to the BAY 2965501 and pembrolizumab with platinum-based regimen combination expansion cohorts:
- All solid cancers, except primary central nervous system cancers (including NSCLC, HNSCC, cervical, endometrial, triple negative breast cancer), that are eligible for standard of care platinum-based regimen
- Previous therapy with a DGK inhibitor other than BAY 2965501 or BAY 2862789 is prohibited. Participants previously treated with BAY 2965501 or BAY 2862789 must have progressed on that DGK inhibitor (given as monotherapy and not have discontinued for toxicity) to be eligible for the combination of BAY 2965501 and pembrolizumab cohorts only.
- 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 4 weeks earlier are also excluded. Participants with known previously treated brain metastases, which are radiologically stable compared to a CT/MRI scan at least 4 weeks earlier, clinically stable and without the requirement of steroid treatment for at least 14 days prior to the first dose of study treatment
- 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.
Clinical Study Information for Healthcare Providers
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