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

Plain English Summary

A First-in-human Study to Learn How Safe the Study Drug BAY2965501 is, Find the Best Dose (Single Drug & Combination), How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, How it Acts on Different Tumors in Participants With Advanced Solid Tumors is a Phase 1 clinical trial sponsored by Bayer studying Advanced Solid Tumors. This study tests a new drug called BAY2965501, alone or with other cancer treatments, in adults with advanced solid tumors. It is for patients with certain types of advanced solid tumors, including some skin, kidney, stomach, and lung cancers. Participation involves taking the study drug orally or as an infusion, with regular check-ups and tests to monitor safety and response. Alternative treatments may include standard chemotherapy, immunotherapy, or targeted therapies, depending on the specific cancer type and prior treatments. The trial aims to enroll 284 participants.

Official Summary

Researchers are looking for a better way to treat people who have advanced solid tumors. Advanced solid tumors are types of cancer that may have spread to nearby tissue, lymph nodes, and/or to distant parts of the body and that are unlikely to be cured or controlled with currently available treatments. This study focuses on certain types of skin cancer, kidney cancer, stomach cancer, and lung cancer. The study treatment BAY2965501 is currently under development as monotherapy or in combination for the treatment of people with advanced solid tumors. BAY2965501 blocks an enzyme in T-cells to activate them. T-cells are a type of immune cell that are known to have an anti-cancer effect and BAY2965501 is a potential new immunotherapy. The main purpose of this first-in-human study is to learn: • how safe different doses of BAY2965501 are when given as a single drug or in combination, • the degree to which medical problems caused by BAY2965501 when given as a single drug or in combination, can be tolerated (also called tolerability), • what maximum amount can be given as a single drug or in combination, and • how it moves into, through and out of the body as a single drug or in combination. To answer this, researchers will look at: • the number and severity of medical problems participants have after taking BAY2965501 as a single drug or in combination for each dose level. These medical problems are also referred to as adverse events. • the (average) total level of BAY2965501 in the blood (also called AUC) after intake of single and multiple doses • the (average) highest level of BAY2965501 in the blood (also called Cmax) after intake of single and multiple doses Doctors keep track of all medical problems that participants have during the study, even if they do not think the medical problem might be related to the study treatment. In addition, the researchers want to know if and how the participants' tumors change after taking BAY2965501. The study will have two parts. The

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with advanced solid tumors that have spread and are not responding to current treatments. Patients must have measurable disease and a good general health status (ECOG 0-1). Specific tumor types are eligible for different parts of the study, including certain lung, stomach, and other solid cancers. Individuals who have had certain prior cancer therapies or have active brain metastases may not be eligible. This trial is studying Advanced Solid Tumors, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measure how safe the study drug is, the highest dose that can be given without causing unacceptable side effects, and how the drug is processed by the body, which helps doctors un The specific primary outcome measures are: The frequency and severity of treatment-emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs) (Up to 90 days after the last administration of study treatment); Maximum Tolerated Dose (MTD): Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level in the dose escalation part of the study (From first dose of study treatment to the end of Cycle 1 (each cycle is 21 days)); Maximum Administered Dose (MAD): Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level in the dose escalation part of the study (From first dose of study treatment to the end of Cycle 1 (each cycle is 21 days)); Maximum concentration (Cmax) of the respective dosing interval of BAY2965501 after single dose and multiple-dose (From pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days)); Area under the curve [AUC (0 - 24)] of the respective dosing interval of BAY 2965501 after single-dose and multiple-dose (From pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial is important because it explores a new immunotherapy drug, BAY2965501, which targets T-cells to fight cancer, potentially filling a gap for patients with advanced solid tumors who have limi This research targets Advanced Solid Tumors, where improved treatment options are needed.

Investor Insight

This Phase 1 trial represents an early-stage investment signal for Bayer's novel immunotherapy, BAY2965501, targeting a potentially large market of advanced solid tumors, with approval probability dep Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of BAY2965501, how it will be administered, and what to expect during the study. Participation involves regular visits for drug administration, blood tests, imaging scans, and monitoring for side effects. You will need to take the study drug as prescribed and report any new or worsening symptoms to the study team immediately. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 284 participants

Interventions

• DRUG: BAY2965501 — Daily oral application
• DRUG: Pembrolizumab — In combination group 200mg as infusion every 3 weeks
• DRUG: Platinum-based Chemotherapy — Standard of care doses per tumor type will be administered.

Primary Outcomes

• The frequency and severity of treatment-emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs) (Up to 90 days after the last administration of study treatment)
• Maximum Tolerated Dose (MTD): Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level in the dose escalation part of the study (From first dose of study treatment to the end of Cycle 1 (each cycle is 21 days))
• Maximum Administered Dose (MAD): Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level in the dose escalation part of the study (From first dose of study treatment to the end of Cycle 1 (each cycle is 21 days))
• Maximum concentration (Cmax) of the respective dosing interval of BAY2965501 after single dose and multiple-dose (From pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days))
• Area under the curve [AUC (0 - 24)] of the respective dosing interval of BAY 2965501 after single-dose and multiple-dose (From pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days))

Secondary Outcomes

• Objective response rate (ORR) (Approximately 6 months)
• Disease control rate (DCR) (Approximately 6 months)
• Duration of response (DOR) (Approximately 6 months)
• Progression-free survival (PFS) rate at 6 months (At 6 months)
• Overall survival (OS) rate at 12 months (At 12 months)

Full Eligibility Criteria

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

Exclusion Criteria:

* 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.

Trial Locations

• Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's, Denver, Colorado, United States
• UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, United States
• START | San Antonio, San Antonio, Texas, United States
• Antwerp University Hospital | Oncology Department, Antwerp, Belgium
• Ghent University Hospital | Drug Research Unit Department, Ghent, Belgium
• Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department, Hangzhou, Zhejiang, China
• Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China
• National Cancer Center Hospital East, Kashiwa, Chiba, Japan
• Seoul National University Bundang Hospital, Seongnam-si, Gyeonggido, South Korea
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Advanced Solid Tumors
• Non-small cell lung cancer (NSCLC)
• Skin Cancer
• Kidney Cancer
• Stomach Cancer
• Head and Neck Squamous Cell Cancer (HNSCC)
• Cervical Cancer
• Endometrial Cancer
• Triple Negative Breast Cancer
• Gastrointestinal Adenocarcinoma

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