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

NCT05614102 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: 219482023-507905-33-002022-002016-23
• Study Type: interventional
• Target: 284
• Locations: 7 countries
• Sites: 21

Brief 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 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.

Conditions

Advanced Solid Tumors

Keywords

Solid tumors; Non-small cell lung cancer; NSCLC; Gastroesophageal junction adenocarcinoma; GEJ adenocarcinoma; Renal cell carcinoma; RCC; Melanoma

Outcome Measures

Primary Outcomes (5)

• 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

  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)

Secondary Outcomes (7)

• 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

Study Arms (6)

Dose escalation of BAY2965501

EXPERIMENTAL

For escalation part, different dose levels of BAY2965501 are planned.

Drug: BAY2965501

Dose expansion of BAY2965501

EXPERIMENTAL

For expansion part, specific tumor types are recruited: NSCLC (non-small cell lung cancer).

Drug: BAY2965501

Dose escalation of BAY2965501+pembrolizumab

EXPERIMENTAL

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

Dose expansion of BAY2965501 +pembrolizumab

EXPERIMENTAL

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

Dose escalation of BAY 2965501 + pembrolizumab + platinum-based regimen

EXPERIMENTAL

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

Dose expansion of BAY 2965501 + pembrolizumab + platinum-based regimen

EXPERIMENTAL

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

Interventions

BAY2965501 DRUG

Daily oral application

Dose escalation of BAY2965501; Dose expansion of BAY2965501

Pembrolizumab DRUG

In combination group 200mg as infusion every 3 weeks

Dose escalation of BAY2965501+pembrolizumab; Dose expansion of BAY2965501 +pembrolizumab

Platinum-based Chemotherapy DRUG

Standard of care doses per tumor type will be administered.

Dose escalation of BAY 2965501 + pembrolizumab + platinum-based regimen; Dose expansion of BAY 2965501 + pembrolizumab + platinum-based regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (21)

Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's

Denver, Colorado, 80218, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

START | San Antonio

San Antonio, Texas, 78229, United States

Location

Antwerp University Hospital | Oncology Department

Antwerp, 2650, Belgium

Location

Ghent University Hospital | Drug Research Unit Department

Ghent, 9000, Belgium

Location

Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department

Hangzhou, Zhejiang, 310016, China

Location

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, 100000, China

Location

Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center

Shenzhen, 518172, China

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, 13620, South Korea

Location

Severance Hospital, Yonsei University Health System - Oncology Department

Seoul, Seoul Teugbyeolsi, 03722, South Korea

Location

Samsung Medical Center - Oncology Department

Seoul, 135-710, South Korea

Location

Clinica Universidad De Navarra | Pamplona | Oncologia

Pamplona, Madrid, 31008, Spain

Location

Hospital Hm Nou Delfos | Oncologia

Barcelona, 08023, Spain

Location

Hospital Universitari Vall D Hebron | Oncologia

Barcelona, 08035, Spain

Location

Clinica Universidad De Navarra | Madrid | Oncologia

Madrid, 28027, Spain

Location

Hospital Universitario Hm Sanchinarro | Oncologia

Madrid, 28050, Spain

Location

Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital

London, Greater London, SE1 9RT, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust | Churchill Hospital - Oncology

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Royal Marsden NHS Trust (Surrey)

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Melanoma

Interventions

pembrolizumab; Platinum Compounds

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Inorganic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2022
• First Posted: November 14, 2022
• Study Start: November 4, 2022
• Primary Completion (Estimated): May 21, 2026
• Study Completion (Estimated): April 14, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); KR (3); JP (1); BE (2); CN (3); ES (5); GB (4)