Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab

Conditions

Advanced Cancer

Keywords

Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Breast Cancer, Urothelial Carcinoma, Nasopharyngeal Carcinoma, Cervical Cancer, Lymphoma

Brief 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. 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.

Eric Liu, Amit Verma, Kith Pradhan, Urvi A. Shah, Aditi Shastri et al. (10 authors)

Blood2024-11-05

10.1182/blood-2024-210385

Abstract CT226: Phase 2 study of oral CCR4 antagonist FLX475 (tivumecirnon) plus pembrolizumab in subjects with head and neck squamous cell carcinoma (HNSCC) previously treated with checkpoint inhibitor

Jameel Muzaffar, Kedar Kirtane, Rebecca Redman, Muh‐Hwa Yang, Tae Min Kim et al. (19 authors)

Cancer Research2024-04-055 citations

10.1158/1538-7445.am2024-ct226

Abstract 2485: A combined mregDC and Treg signature associates with antitumor efficacy of CCR4 antagonist tivumecirnon FLX475

Adam Grant, Juraj Adamik, Jingtao Qiu, J.P. Perez Wert, Molly Grandcolas et al. (17 authors)

Cancer Research2024-03-221 citations

10.1158/1538-7445.am2024-2485

North American Adult T-Cell Leukemia/Lymphoma Has Frequent Mutations in CCR4 and Responds in Vitro to a Small Molecule CCR4 Antagonist, CCR4-351

B. Hilda Ye, Eric Liu, Kith Pradhan, Erik Guillen, Urvi A. Shah et al. (11 authors)

Blood2023-11-02

10.1182/blood-2023-191045

629-C Phase 2 safety and efficacy of oral CCR4 antagonist FLX475 (tivumecirnon) plus pembrolizumab in subjects with non-small cell lung cancer not previously treated with checkpoint inhibitor

Tae Min Kim, Nuttapong Ngamphaiboon, Ki Hyeong Lee, Pratibha Desai, Chia‐Chi Lin et al. (15 authors)

2023-10-312 citations

10.1136/jitc-2023-sitc2023.0629-c

704 Biological activity of FLX475, an oral CCR4 antagonist, as monotherapy and in combination with pembrolizumab in advanced cancer

Juraj Adamik, Adam Grant, Damian Trujillo, Rakesh K. Goyal, William W. Ho et al. (15 authors)

Regular and Young Investigator Award Abstracts2023-10-311 citations

10.1136/jitc-2023-sitc2023.0704

Clinical and biological activity of FLX475, an oral CCR4 antagonist, in advanced cancer.

Dirk G. Brockstedt, Adam Grant, Juraj Adamik, Damian Trujillo, Rakesh K. Goyal et al. (11 authors)

Journal of Clinical Oncology2023-06-011 citations

10.1200/jco.2023.41.16_suppl.2625

Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer.

John D. Powderly, Bartosz Chmielowski, Julie R. Brahmer, Sarina A. Piha‐Paul, Samantha Bowyer et al. (13 authors)

Journal of Clinical Oncology2020-05-204 citations

10.1200/jco.2020.38.15_suppl.tps3163

Phase I/II dose escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer.

William Ho, Nicole Nasrah, Daniel M. Johnson

Journal of Clinical Oncology2019-03-107 citations

10.1200/jco.2019.37.8_suppl.tps24

Interventions

DRUGFLX475 (tivumecirnon)

tablet

DRUGpembrolizumab (KEYTRUDA®)

IV infusion

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* 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

Exclusion criteria

* 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

Design outcomes

Primary

Measure	Time frame	Description
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	Approximately 18 weeks	treatment-emergent adverse events
Overall Response Rate in Subjects Treated With FLX475 as a Single Agent and in Combination With Pembrolizumab	Through study completion (approximately 2 years)	Summary of Best Overall Response

Countries

Australia, Hong Kong, South Korea, Taiwan, Thailand, United States

Contacts

STUDY_DIRECTORWilliam Ho, MD, PhD

RAPT Therapeutics, Inc.

Baseline characteristics

Characteristic	—
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	105 Participants
Age, Categorical Between 18 and 65 years	218 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	8 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	88 Participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk	EG017 affected / at risk	EG018 affected / at risk	EG019 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 3	0 / 7	0 / 6	0 / 3	0 / 4	2 / 11	0 / 12	0 / 20	1 / 13	0 / 11	1 / 21	0 / 30	4 / 32	2 / 24	0 / 15	3 / 46	2 / 40	0 / 12	2 / 10
other Total, other adverse events	2 / 3	3 / 3	6 / 7	6 / 6	3 / 3	2 / 4	8 / 11	8 / 12	14 / 20	10 / 13	9 / 11	12 / 21	25 / 30	23 / 32	18 / 24	10 / 15	36 / 46	31 / 40	7 / 12	8 / 10
serious Total, serious adverse events	0 / 3	0 / 3	0 / 7	0 / 6	0 / 3	0 / 4	1 / 11	0 / 12	0 / 20	1 / 13	0 / 11	0 / 21	3 / 30	2 / 32	3 / 24	1 / 15	3 / 46	2 / 40	2 / 12	1 / 10

Outcome results

None listed