What side effects are associated with this type of intervention?

Common treatments for solid tumors, such as PD-1/PD-L1 inhibitors (e.g., pembrolizumab), often lead to immune-related adverse events (irAEs). These can include skin reactions (rash, pruritus), gastrointestinal issues (diarrhea, colitis), and endocrine disorders (thyroid dysfunction). When combined with a CCR8 antibody like BAY3375968, additional side effects may include a reduction in regulatory T cells, potentially leading to enhanced immune responses and associated toxicities. Monitoring for these side effects is crucial to manage and mitigate potential risks.

What prior FDA approvals exist?

Pembrolizumab (Keytruda) and Ipilimumab (Yervoy) are FDA-approved immunotherapies for the treatment of various solid tumors, including melanoma and non-small cell lung cancer. These drugs enhance the immune system's ability to target and destroy cancer cells by inhibiting immune checkpoints such as PD-1 and CTLA-4. This mechanism is similar to the investigational drug BAY3375968, which aims to reduce regulatory T cells by targeting CCR8, thereby strengthening the immune response against cancer.

What other types of research exist?

Promising alternatives to BAY3375968 for solid tumor patients include: 1) Pembrolizumab (PD-1 inhibitor) combined with chemotherapy, which has shown efficacy in various solid tumors. 2) Nivolumab (PD-1 inhibitor) combined with ipilimumab (CTLA-4 inhibitor), which has demonstrated benefits in melanoma and renal cell carcinoma. 3) Atezolizumab (PD-L1 inhibitor) combined with bevacizumab (VEGF inhibitor), which has shown promise in renal cell carcinoma. 4) Relatlimab (LAG-3 inhibitor) combined with nivolumab, which has shown efficacy in melanoma. These therapies leverage different mechanisms to enhance the immune response against cancer cells.

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Monoclonal Antibodies

BAY3375968 + Pembrolizumab for Advanced Cancer

Phase 1

Recruiting

Research Sponsored by Bayer

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 60 months

Awards & highlights

Study Summary

This trial is studying a new way to treat people with advanced solid tumors by using immunotherapy with PD-1/PD-L1 inhibitors and an antibody that binds to a protein called CCR8.

Who is the study for?

This trial is for adults with advanced solid tumors that have spread and are not curable with existing treatments. Participants must be physically capable of daily activities (ECOG PS 0 or 1), have functioning organs, agree to use contraception if applicable, and not be pregnant or breastfeeding. They should have tried all other effective treatments without success.Check my eligibility

What is being tested?

The study tests BAY3375968 alone and combined with Pembrolizumab in two parts: dose escalation to find the safest high dose, then dose expansion at this best dose focusing on lung, breast, head/neck cancer, and melanoma. It measures safety, tolerability, how the body processes the drug, optimal dosing levels, and anti-cancer effects.See study design

What are the potential side effects?

Potential side effects include typical reactions from immunotherapy such as fatigue; skin reactions; digestive issues like nausea or diarrhea; potential immune-related problems affecting lungs or liver; infusion-related symptoms; changes in blood counts leading to increased infection risk.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 60 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Area under the concentration-time curve (AUC) of BAY3375968

Maximum tolerated dose (MTD) or Maximum administered dose (MAD)

Number of participants experiencing dose-limiting toxicity (DLTs) at each dose level in the dose-escalation part of the study

+3 more

Secondary outcome measures

Fold change in intratumor CD8+ T cell/Treg ratio (as measured by IHC [Immunohistochemistry]) in on-treatment compared with baseline tumor biopsies

Fold change in serum IFN (Interferon)-γ (as measured by immune-based assay) in on-treatment compared with baseline serum samples

Objective response rate (ORR)

+1 more

Side effects data

From 2024 Phase 2 trial • 57 Patients • NCT03004183

21%

Fatigue

13%

Nausea

11%

Back pain

Shortness of Breath

Anemia

Abdominal pain

Diarrhea

Pneumonia

Kidney Injury and/or Infection

Dyspnea

Weight Loss

Pneumothorax

Malnutrition, Hypercalcemia and Weakness

Intractable pain, back pain, hip pain

Activated partial thromboplastin time prolonged

Pleural effusion

Atrial fibrillation with rapid ventricular response

Thrombocytopenia

Respiratory failure

Skin rash

colitis

100%

80%

60%

40%

20%

Study treatment Arm

Single Arm

Trial Design

4Treatment groups

Experimental Treatment

Group I: Dose expansion - Arm 2BExperimental Treatment2 Interventions

Disease-specific combination expansion with separate cohorts in 4 ICI-relapsed tumor types (NSCLC, TNBC, HNSCC, and melanoma)

Group II: Dose expansion - Arm 2AExperimental Treatment1 Intervention

BAY3375968 monotherapy-mode-of-action (monotherapy-MoA) expansion in subjects with one of the following tumor types: NSCLC (PD-L1 tumor proportion score [TPS] ≥50%), TNBC (PD-L1 combined positive score [CPS] ≥10), HNSCC (PD-L1 CPS ≥20), or melanoma (no PD-L1 cut-off). The tumors should have primary (ICI-refractory) or secondary (ICI-relapsed) resistance to prior ICI-therapy. The final decision on the enrolled tumor type is at the discretion of the Sponsor.

Group III: Dose escalation - Arm 1BExperimental Treatment2 Interventions

Dose escalation of BAY 3375968 in combination with pembrolizumab

Group IV: Dose escalation - Arm 1AExperimental Treatment1 Intervention

Dose escalation of BAY3375968 as monotherapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 2

~2010

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors often involve immunotherapies that enhance the body's immune response to cancer. PD-1/PD-L1 inhibitors, for example, block proteins that prevent immune cells from attacking cancer cells. BAY3375968, an investigational drug, targets the CCR8 protein on regulatory T cells, reducing their suppressive effect on the immune system and thereby strengthening the immune response against tumors. These mechanisms are vital for solid tumor patients as they can potentially improve the effectiveness of cancer treatments and lead to better clinical outcomes.

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