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

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

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 first part, called dose escalation, is done to find the most appropriate dose that can be given in the second part. For this, participants will be assigned to receive one of the planned doses and schedules of BAY2965501 as single drug or participants will be assigned to one of the increasing doses of BAY2965501 in combination with 200mg pembrolizumab. Additionally, platinum based chemotherapy as decided by the treating investigator will be given within the first months (at minimum 2 cycles and up to 6 cycles maximum). Here participants will receive BAY 2965501 in combination with pembrolizumab and platinum based chemotherapy.

All participants will take BAY2965501 by mouth. Additionally, in combination group 1, pembrozilumab will be given as infusion using a small tube that goes into your vein. In combination group 2, pembrolizumab and platinum based chemotherapy will be given as infusion using a small tube that goes into your vein.

In the second part, called dose expansion, all participants in the single drug group will receive up to 2 of the most appropriate doses of BAY2965501 from the 1st part as tablet by mouth. The participants in the combination groups (group 1: + pembrozilumab; group 2: + pembrolizumab and platinum based chemotherapy) will receive the most appropriate dose of BAY2965501 from the first part. Participants in both parts of the study, will take the study treatment until the tumor gets worse (also known as 'disease progression'), or until the participants have medical problems. In general, the study treatment is planned for a maximum of 35 cycles. Each participant will be in the study for several months, including a screening phase of up to 28 days, few months of treatment depending on the participant's benefit, and a follow up phase after the end of treatment. Participants in part two will be assigned to one of 3 groups depending on cancer characteristics.During the study, the study team will: • take blood and urine samples • do physical examinations • check vital signs such as blood pressure, heart rate, body temperature • examine heart health using ECG (electrocardiogram) • check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan • take tumor samples (if required) The treatment period ends with a visit no later than 7 days after the last BAY2965501 dose in the single drug and combination group. About 30 and 90 days after the last dose and every 12 weeks thereafter, the study team will check the participants' health and any changes in cancer. This follow-up period ends with worsening of the cancer, start of new anti-cancer therapy, or until the participant leaves the study.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: BAY2965501; Drug: Pembrolizumab; Drug: Platinum-based Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 284
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2650
    • Antwerp University Hospital | Oncology Department
  • Ghent, Belgium, 9000
    • Ghent University Hospital | Drug Research Unit Department
• China
  • Beijing, China, 100000
    • Cancer hospital, Chinese Academy of Medical Sciences
  • Shenzhen, China, 518172
    • Cancer Hospital Chinese Academy of Medical Sciences, ShenZhen center
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
• South Korea
  • Seoul, South Korea, 135-710
    • Samsung Medical Center - Oncology Department
  • Gyeonggido
    • Seongnam-si, Gyeonggido, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03722
      • Severance Hospital, Yonsei University Health System - Oncology Department
• Spain
  • Barcelona, Spain, 08023
    • Hospital Hm Nou Delfos | Oncologia
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall D Hebron | Oncologia
  • Madrid, Spain, 28050
    • Hospital Universitario Hm Sanchinarro | Oncologia
  • Madrid, Spain, 28027
    • Clinica Universidad De Navarra | Madrid | Oncologia
  • Madrid
    • Pamplona, Madrid, Spain, 31008
      • Clinica Universidad De Navarra | Pamplona | Oncologia
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE1 9RT
      • Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Oxford University Hospitals NHS Foundation Trust | Churchill Hospital - Oncology
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden NHS Trust (Surrey)
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
      • Freeman Hospital
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • START | San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation of BAY2965501; For escalation part, different dose levels of BAY2965501 are planned.	Drug: BAY2965501; Daily oral application
Experimental: Dose escalation of BAY2965501+pembrolizumab; For escalation part different dose levels of BAY2965501 are planned in combination with 200mg pembrolizumab. BAY2965501 will be taken in combination with 200mg pembrolizumab every 3 weeks.	Drug: Pembrolizumab; In combination group 200mg as infusion every 3 weeks
Experimental: Dose expansion of BAY2965501 +pembrolizumab; For expansion part, specific tumor types are recruited (non-small cell lung cancer (NSCLC) and gastric/gastroesophageal junction (GEJ) adenocarcinoma). BAY2965501 will be taken in combination with 200mg pembrolizumab every 3 weeks.	Drug: Pembrolizumab; In combination group 200mg as infusion every 3 weeks
Experimental: Dose escalation of BAY 2965501 + pembrolizumab + platinum-based regimen; The starting dose of BAY 2965501 with pembrolizumab for this combination will be no higher than one dose level below that shown to be safe in BAY 2965501 and pembrolizumab dose escalation. The doses of platinum-based regimen will be as per standard of care and given for a maximum of 6 cycles, in line with the current labeled dose. The dose of pembrolizumab will be 200 mg every 3 weeks, in line with the current labeled dose.	Drug: Platinum-based Chemotherapy; Standard of care doses per tumor type will be administered.
Experimental: Dose expansion of BAY 2965501 + pembrolizumab + platinum-based regimen; Participants with selected (to be decided by the sponsor) advanced solid tumors will be recruited in a dose expansion cohort of BAY 2965501 with pembrolizumab and platinum-based regimen.	Drug: Platinum-based Chemotherapy; Standard of care doses per tumor type will be administered.
Experimental: Dose expansion of BAY2965501; For expansion part, specific tumor types are recruited: NSCLC (non-small cell lung cancer).	Drug: BAY2965501; Daily oral application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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	If AUC(0-24) cannot be calculated reliably, it might become necessary to appoint the additional parameter AUC(0-tlast) as primary variable.	From pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days)
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)	Approximately 6 months
Disease control rate (DCR)	Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)	Approximately 6 months
Duration of response (DOR)	Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)	Approximately 6 months
Change from baseline in peripheral activation of effector T memory cells as assessed by flow cytometry		From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Change from baseline in interleukin 2 and interferon-gamma levels after ex-vivo stimulation		Screening, Cycle 1: Day 1, Day 8 (each cycle is 21 days)
Progression-free survival (PFS) rate at 6 months	Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)	At 6 months
Overall survival (OS) rate at 12 months		At 12 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2022
• Primary Completion (Estimated): May 21, 2026
• Study Completion (Estimated): April 14, 2027

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: November 10, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Solid tumors; Non-small cell lung cancer; Melanoma; Renal cell carcinoma; Gastroesophageal junction adenocarcinoma; RCC; GEJ adenocarcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Melanoma; Inorganic Chemicals; Platinum Compounds; pembrolizumab
• Other Study ID Numbers: 21948; 2022-002016-23 (EudraCT Number); 2023-507905-33-00 (Other Identifier: EU-CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No