FLX475 + Pembrolizumab for Tumors/Cancer

No longer recruiting at 45 trial locations
CT
Overseen ByClinical Trial Manager
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: RAPT Therapeutics, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and early effectiveness of a new drug, FLX475, both alone and with pembrolizumab (an immunotherapy drug), to evaluate their impact on certain advanced or spreading cancers. The study has two parts: first, to determine the optimal dose of FLX475, and second, to assess its effectiveness alone or with pembrolizumab. It seeks participants with specific cancers, such as lung, head and neck, or cervical cancer, who have not responded to standard treatments. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that FLX475, whether used alone or with pembrolizumab, is generally safe for people. In earlier studies, patients taking FLX475 alone found it safe and well-tolerated. When combined with pembrolizumab, it was also considered safe, and patients managed the treatment well.

Reports indicate that both FLX475 alone and with pembrolizumab have not caused major safety issues, meaning most patients can handle these treatments. However, individual experiences can differ, so discussing any concerns with a doctor is important.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about FLX475 in combination with pembrolizumab because it offers a novel approach to cancer treatment. Unlike existing therapies, which often target cancer cells directly, FLX475 works by blocking a particular chemokine receptor called CCR4. This action prevents the recruitment of regulatory T cells that typically suppress the immune response against tumors. By combining FLX475 with pembrolizumab, an immune checkpoint inhibitor, the treatment aims to amplify the body's natural immune response to recognize and attack cancer cells more effectively. This dual approach could potentially enhance the effectiveness of immunotherapy and offer new hope for patients with challenging tumors.

What evidence suggests that this trial's treatments could be effective for tumors?

Research has shown that FLX475 may help treat cancer by targeting and reducing certain cells (Treg cells) that can weaken the immune system's ability to fight tumors. Patients using FLX475 have experienced changes in their immune systems that might help the body combat cancer more effectively. Studies also indicate that FLX475 can change the environment around tumors, supporting the body's natural defenses against cancer. In this trial, some participants will receive FLX475 as monotherapy, while others will receive a combination of FLX475 and pembrolizumab. Early results for this combination showed promise in treating various types of tumors.13678

Who Is on the Research Team?

WH

William Ho, MD, PhD

Principal Investigator

RAPT Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers (like lung, breast, or lymphoma) who can't be helped by standard treatments. They should be fairly active and well (ECOG 0-1), have tumors that can be measured on scans, and a tumor sample available. People with severe past reactions to immune therapies, serious lung conditions, recent organ transplants, or active autoimmune diseases aren't eligible.

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Documented advanced or metastatic cancer ineligible for standard therapies with one of the following histologies: Dose Escalation - non-small cell lung cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, metastatic triple negative breast cancer, urothelial carcinoma, gastric cancer, esophageal carcinoma, cervical cancer, classical Hodgkin lymphoma; Dose Expansion - nasopharyngeal carcinoma, lymphoma, head and neck squamous cell carcinoma, cervical cancer, non-small cell lung cancer, triple-negative breast cancer
Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts)
See 1 more

Exclusion Criteria

You have experienced severe side effects from previous immunotherapy treatments that caused you to stop the treatment.
You have a history of lung diseases like pulmonary fibrosis or pneumonitis, or you currently have symptoms of lung inflammation.
You had a stem cell or organ transplant from someone else within the past 5 years.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects are enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab

Varies

Cohort Expansion

Subjects are enrolled in parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • FLX475
  • Pembrolizumab
Trial Overview The study tests FLX475 alone and combined with pembrolizumab in two parts: first finding the right dose of FLX475 (dose escalation), then giving it to more people at this dose to see how well it works and how safe it is (cohort expansion).
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Part 2b: Combination Expansion CohortsExperimental Treatment2 Interventions
Group II: Part 2a: Monotherapy Expansion CohortsExperimental Treatment1 Intervention
Group III: Part 1b: Combination Dose EscalationExperimental Treatment2 Interventions
Group IV: Part 1a: Monotherapy Dose EscalationExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

RAPT Therapeutics, Inc.

Lead Sponsor

Trials
7
Recruited
800+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

A phase 2 study to assess the safety and efficacy of ...The median time to response (mTTR) was 2.7 months, with a median duration of response (mDOR) of 17.3 months. The median progression-free ...
RAPT Therapeutics to Present Biomarker Data ...-FLX475-treated patients exhibited significant changes in immune pathways likely to enhance an antitumor response.
Clinical and biological activity of FLX475, an oral CCR4 ...Consistent with the proposed mechanism of action, immune deconvolution identified that FLX475-treated patients experienced a decrease in Treg cell populations.
704 Biological activity of FLX475, an oral CCR4 antagonist ...These data support the beneficial effects of FLX475 in modification of the TME and promotion of anti-cancer immunity. Methods and Results As ...
Phase 2 study of oral CCR4 antagonist FLX475 (tivumecirnon ...Additional efficacy endpoints included progression-free survival (PFS). Safety was evaluated as per CTCAE v4.03. Data cutoff was 11DEC2023.
Pharmacokinetics, Pharmacodynamics, and Safety of ...In this first-in-human HV study, the oral CCR4 antagonist FLX475 was demonstrated to be well tolerated with outstanding PK properties. A robust PD assay ...
629-C Phase 2 safety and efficacy of oral CCR4 antagonist ...Early encouraging data on the biologic effects, safety and antitumor activity of FLX475 have previously been presented.1–4 We now present the ...
Phase I/II dose escalation and expansion study of FLX475 alone ...... tumors via CCR4 signaling. These human PK, PD, and safety data have enabled a streamlined design of a Phase 1/2 study of FLX475 in cancer patients both as ...
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