A First-in-human Study to Learn How Safe the Study Treatment BAY2965501 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors
Study Details
Study Description
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 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:
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how safe different doses of BAY2965501 are,
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the degree to which medical problems caused by BAY2965501 can be tolerated (also called tolerability),
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what maximum amount can be given, and
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how it moves into, through and out of the body.
To answer this, the researchers will look at:
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the number and severity of medical problems participants have after taking BAY2965501 for each dose level. These medical problems are also referred to as adverse events.
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the (average) total level of BAY2965501 in the blood (also called AUC) after intake of single and multiple doses
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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, 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. Participants in both parts of the study, will take the study treatment until the tumor gets worse (also known as 'disease progression'), the participants have medical problems, until they leave the study, or until the study is terminated.
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. The following approximate numbers of visits to the study site are planned: two during the screening phase, six in the first treatment month, one to three per month in the following periods.
Participants in part 2 will be assigned to one of four groups depending on cancer characteristics.
Study procedures described below may vary between these groups.
During the study, the study team will:
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take blood and urine samples
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do physical examinations
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check vital signs such as blood pressure, heart rate, body temperature
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examine heart health using ECG (electrocardiogram)
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check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan
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take tumor samples (if required)
The treatment period ends with a visit no later than 7 days after the last BAY2965501 dose. 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. In addition, the study doctors and their team will contact the participant every 12 weeks to learn about the participant's survival. This ends no later than 12 months after the last participant started treatment or by the end of the study, whichever comes first.
If the study participant benefits from treatment, continuation of treatment with BAY2965501 beyond the duration of this study might be possible.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| 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 expansion of BAY2965501 For expansion part, specific tumor types are recruited (non-small cell lung cancer (NSCLC) and gastric/gastroesophageal junction (GEJ) adenocarcinoma). |
Drug: BAY2965501
Daily oral application
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs) and their severity [Up to 90 days after the last administration of study treatment]
- 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)]
- Recommended Phase 2 dose (RP2D) of BAY2965501 [Up to 90 days after the last administration of study treatment]
- Maximum concentration (Cmax) of the respective dosing interval of BAY2965501 after single 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)] for once daily (QD) dosing of BAY2965501 after single dose in Cycle 1 [From pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days)]
If AUC(0-24) and AUC(0-12) cannot be calculated reliably, it might become necessary to appoint the additional parameter AUC(0-tlast) as primary variable.
- Area under the curve [AUC(0-12)] for 2 times daily (BID) dosing after single dose in Cycle 1 (if applicable)) [From pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days)]
If AUC(0-24) and AUC(0-12) cannot be calculated reliably, it might become necessary to appoint the additional parameter AUC(0-tlast) as primary variable.
- Maximum concentration (Cmax,md) of the respective dosing interval of BAY2965501 after multiple dose [From pre-dose up to 24 hours after administration on Cycle 1 Day 15 (each cycle is 21 days)]
- Area under the curve [AUC(0-24)md] for QD dosing of BAY2965501 after multiple dose [From pre-dose up to 24 hours after administration on Cycle 1 Day 15 (each cycle is 21 days)]
If AUC(0-24)md, AUC(0-12)md cannot be calculated reliably, it might become necessary to appoint the additional parameter AUC(0-tlast)md as primary variable.
- Area under the curve [AUC(0-12)md] for BID dosing of BAY2965501 after multiple dose (if applicable) [From pre-dose up to 24 hours after administration on Cycle 1 Day 15 (each cycle is 21 days)]
If AUC(0-24)md, AUC(0-12)md cannot be calculated reliably, it might become necessary to appoint the additional parameter AUC(0-tlast)md as primary variable.
Secondary Outcome Measures
- Objective response rate (ORR) [Approximately 6 months]
Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)
- Disease control rate (DCR) [Approximately 6 months]
Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)
- Duration of response (DOR) [Approximately 6 months]
Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)
- Progression-free survival (PFS) rate [At 6 months]
Investigator assessment using Response Evaluation Criteria in Solid Tumours version (RECIST 1.1)
- Overall survival (OS) rate [At 12 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)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Be 18 years of age on day of signing informed consent.
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Have measurable disease per Response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) as assessed by the local site investigator.
Lesions situated in a previously irradiated area or in an area subjected to locoregional therapy are considered measurable if progression has been demonstrated in such lesions.
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Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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Participants with histologically confirmed diagnosis of a solid tumor will be enrolled onto this study. For expansion part, specific tumor types are recruited (non-small cell lung cancer (NSCLC) and gastric/gastroesophageal junction (GEJ) adenocarcinoma).
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Provision of archival tumor sample at baseline is mandatory for all participants.
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Have adequate organ function.
Exclusion Criteria:
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A woman of child-bearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study treatment. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
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Previous therapy with a diacylglycerol kinase (DGK) inhibitor.
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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 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).
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Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives, whatever is shorter, prior to treatment. Growth factor treatments such as G-CSF must have been discontinued 4 weeks prior to entering the study.
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Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
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Use of moderate and strong CYP1A1 inhibitors and inducers from 14 days prior to first administration of study drug. Moderate and strong CYP1A1 inhibitors and inducers are prohibited during the study and until Safety Follow Up visit.
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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.
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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).
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Has a history of short bowel syndrome, bowel obstruction or tumor bowel involvement.
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Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. Steroid inhalers are allowed.
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Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
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A marked prolongation of QT/QTc interval at screening (e.g., repeated demonstration of a QTc interval >470 ms).
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A history of risk factors for torsades de pointes (TdP) (e.g., heart failure, family history of Long QT Syndrome).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sarah Cannon Research Institute at HealthONE | Denver | Colorado | United States | 80218 |
| 2 | South Texas Accelerated Research Therapeutics, LLC | San Antonio | Texas | United States | 78229-3307 |
| 3 | National Cancer Center Hospital East | Kashiwa | Chiba | Japan | 277-8577 |
| 4 | Churchill Hospital | Oxford | Oxfordshire | United Kingdom | OX3 7LJ |
| 5 | Royal Marsden NHS Trust (Surrey) | Sutton | Surrey | United Kingdom | SM2 5PT |
| 6 | Freeman Hospital | Newcastle Upon Tyne | Tyne And Wear | United Kingdom | NE7 7DN |
Sponsors and Collaborators
- Bayer
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 21948
- 2022-002016-23