Advanced CancerPhase 1/2NCT03674567
Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab
A Phase 1/2 study testing FLX475 (tivumecirnon) and pembrolizumab (KEYTRUDA®) in people with Advanced Cancer, run by RAPT Therapeutics, Inc., a member of the GSK plc group of companies at 35 sites in 6 countries.
Trial summary
This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- FLX475 (tivumecirnon) and pembrolizumab (KEYTRUDA®)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 323 participants
- Where
- 35 sitesin 6 countries
- Study dates
- 25 Sep 2018to 31 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts)
- Tumor available for biopsy
Who cannot join
- History of allergy or severe hypersensitivity to biologic agents
- History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immuno-oncology treatment
- Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or symptoms of active pneumonitis
- Prior allogeneic hematopoietic stem cell transplant within 5 years, or prior allogeneic organ transplant
- Active graft-versus-host disease
Trial locations and contacts
35 sites in 6 countries.
35 sites in 6 countries
United States19 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory Winship Cancer Institute
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21231
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago
Chicago, Illinois, 60637
Mary Crowley Cancer Research Center
Dallas, Texas, 75230
City of Hope
Duarte, California, 91010
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Carolina BioOncology Institute
Huntersville, North Carolina, 28078
University of California, Los Angeles JCCC Clinical Research Unit
Los Angeles, California, 90024
University of Louisville Hospital/James Graham Brown Cancer Center
Louisville, Kentucky, 40202
Yale Cancer Center
New Haven, Connecticut, 06510
New York Presbyterian Hospital-Columbia University Medical Center
New York, New York, 10032
Quantum Santa Fe
Santa Fe, New Mexico, 87505
University of Washington
Seattle, Washington, 98195
Comprehensive Hematology and Oncology, LLC
St. Petersburg, Florida, 33709
Moffitt Cancer Center
Tampa, Florida, 33612
Georgetown - Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
South Korea5 sites
Chungbuk National University Hospital
Jungbuk, 28644
Seoul National University
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Taiwan4 sites
National Cheng Kung University Hospital
Tainan, 70403
Chi Mei Meidcal Center
Tainan, 71004
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 11217
Hong Kong3 sites
Queen Mary Hospital - Lymphoma
High West
Queen Mary Hospital
High West
Prince of Wales Hospital
Shatin
Australia2 sites
Austin Hospital
Heidelberg, Victoria, 3084
Linear Clinical Research Limited
Nedlands, Western Australia, 6009
Thailand2 sites
King Chulaongkorn Memorial Hospital
Bangkok, 10330
Ramathibodi Hospital
Bangkok, 10400
About this study
Official title: Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer
This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab.
The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.
- Conditions
- Advanced Cancer
- Being tested
- FLX475 (tivumecirnon), pembrolizumab (KEYTRUDA®)
- Keywords
- Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Breast Cancer, Urothelial Carcinoma, Nasopharyngeal Carcinoma, Cervical Cancer, Lymphoma
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Breast Neoplasms, Carcinoma, Transitional Cell, Nasopharyngeal Carcinoma, Uterine Cervical Neoplasms, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLX475 (tivumecirnon)Drug
tablet
pembrolizumab (KEYTRUDA®)Drug
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1a: Monotherapy Dose Escalation | Experimental | Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy. Receives: Drug: FLX475 (tivumecirnon) |
| Part 1b: Combination Dose Escalation | Experimental | Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab. Receives: Drug: FLX475 (tivumecirnon); Drug: pembrolizumab (KEYTRUDA®) |
| Part 2a: Monotherapy Expansion Cohorts | Experimental | Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2. Receives: Drug: FLX475 (tivumecirnon) |
| Part 2b: Combination Expansion Cohorts | Experimental | Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2. Receives: Drug: FLX475 (tivumecirnon); Drug: pembrolizumab (KEYTRUDA®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of FLX475 as a Single Agent and in Combination With Pembrolizumab Measured by the Incidence of Adverse Events, Including Dose-limiting Toxicities and Maximum Tolerated Dose
treatment-emergent adverse events
Measured: Approximately 18 weeks
Overall Response Rate in Subjects Treated With FLX475 as a Single Agent and in Combination With Pembrolizumab
Summary of Best Overall Response
Measured: Through study completion (approximately 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2018
- Study start25 Sep 2018
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 323 participants (actual)
Sponsor and investigators
- Lead sponsor
- RAPT Therapeutics, Inc., a member of the GSK plc group of companies
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- William Ho, MD, PhD, Study director, RAPT Therapeutics, Inc., a member of the GSK plc group of companies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03674567
- Sponsor's protocol ID
- FLX475-02
- Other IDs
- KEYNOTE-877, MK-3475-877
- Status last verified
- Aug 2026
- First submitted
- 14 Sep 2018
- Last updated
- 3 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer
- ClinicalTrials.gov ID
- NCT03674567
- Acronym / sponsor ID
- FLX475-02
- Conditions
- Advanced Cancer
- Keywords
- Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Breast Cancer, Urothelial Carcinoma, Nasopharyngeal Carcinoma, Cervical Cancer, Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 323 participants (actual)
- Lead sponsor
- RAPT Therapeutics, Inc., a member of the GSK plc group of companiesIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 25 Sep 2018 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 17 Sep 2018 (actual)
- Results
- Posted 3 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab.
The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1a: Monotherapy Dose Escalation | Experimental | Drug: FLX475 (tivumecirnon)Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy. |
| Part 1b: Combination Dose Escalation | Experimental | Drug: FLX475 (tivumecirnon), Drug: pembrolizumab (KEYTRUDA®)Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab. |
| Part 2a: Monotherapy Expansion Cohorts | Experimental | Drug: FLX475 (tivumecirnon)Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2. |
| Part 2b: Combination Expansion Cohorts | Experimental | Drug: FLX475 (tivumecirnon), Drug: pembrolizumab (KEYTRUDA®)Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Documented advanced or metastatic cancer ineligible for standard therapies with one of the following histologies
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts)
- Tumor available for biopsy
Key exclusion criteria (6 listed)
- History of allergy or severe hypersensitivity to biologic agents
- History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immuno-oncology treatment
- Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or symptoms of active pneumonitis
- Prior allogeneic hematopoietic stem cell transplant within 5 years, or prior allogeneic organ transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FLX475 (tivumecirnon)tablet | Drug | Part 1a: Monotherapy Dose Escalation, Part 1b: Combination Dose Escalation, Part 2a: Monotherapy Expansion Cohorts, Part 2b: Combination Expansion Cohorts |
| pembrolizumab (KEYTRUDA®)IV infusion | Drug | Part 1b: Combination Dose Escalation, Part 2b: Combination Expansion Cohorts |
Primary outcome
Safety and Tolerability of FLX475 as a Single Agent and in Combination With Pembrolizumab Measured by the Incidence of Adverse Events, Including Dose-limiting Toxicities and Maximum Tolerated Dose
Time frame: Approximately 18 weeks
treatment-emergent adverse events
Overall Response Rate in Subjects Treated With FLX475 as a Single Agent and in Combination With Pembrolizumab
Time frame: Through study completion (approximately 2 years)
Summary of Best Overall Response
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Ho, MD, PhD study director
RAPT Therapeutics, Inc., a member of the GSK plc group of companies
35 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FLX475 (tivumecirnon) and pembrolizumab (KEYTRUDA®) in people with Advanced Cancer, run by RAPT Therapeutics, Inc., a member of the GSK plc group of companies at 35 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, South Korea, Taiwan, Hong Kong, Australia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of FLX475 as a Single Agent and in Combination With Pembrolizumab Measured by the Incidence of Adverse Events, Including Dose-limiting Toxicities and Maximum Tolerated Dose (time frame: Approximately 18 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.