FLX475 Combined With Pembrolizumab in Patients With Advanced or Metastatic Gastric Cancer

Conditions

Gastric Cancer

Brief summary

This clinical study is a Phase 2, open-label study to assess the efficacy, safety profile of FLX475 combined with pembrolizumab in patients with advanced or metastatic gastric cancer. This study is designed to assess the potential anti-tumor activity when administered at the 100mg QD of FLX475 with pembrolizumab and will be conducted (2) cohorts as detailed below. * Cohort 1: EBV negative / CPI naïve gastric cancer subjects who have progressed on at least 2 prior systemic treatments for advanced or metastatic gastric cancer * Cohort 2: EBV positive / CPI naïve gastric cancer subjects who had at least 1 prior systemic treatment for advanced or metastatic gastric cancer Approximately 90 subjects may be enrolled across two cohorts to examine the safety and efficacy.

Do‐Youn Oh, Min-Hee Ryu, Jun‐Eul Hwang, Jaeyong Cho, Dae Young Zang et al. (19 authors)

Journal of Clinical Oncology2025-01-27

10.1200/jco.2025.43.4_suppl.426

658 A phase 2 study to assess the safety, efficacy of FLX475 combined with pembrolizumab in patients with advanced or metastatic gastric cancer

Paul Rhee, Do‐Youn Oh, Min Hee Ryu, Jun‐Eul Hwang, Jaeyong Cho et al. (16 authors)

Regular and Young Investigator Award Abstracts2022-11-012 citations

10.1136/jitc-2022-sitc2022.0658

409 Trial in progress: a phase 2 study to assess the safety, efficacy of FLX475 combined with pembrolizumab in patients with advanced or metastatic gastric cancer

Do‐Youn Oh, Min Hee Ryu, Jun‐Eul Hwang, Jaeyong Cho, Dae Young Zang et al. (17 authors)

Regular and Young Investigator Award Abstracts2021-11-013 citations

10.1136/jitc-2021-sitc2021.409

Interventions

DRUGFLX475

tablet

DRUGPembrolizumab

IV infusion

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* All patients must have histologically or cytologically confirmed, advanced, relapsed or metastatic gastric or gastroesophageal junction adenocarcinoma * Patient must have one of the following diagnoses to be eligible for enrollment into cohorts: * Cohort 1: Checkpoint inhibitor naïve Epstein-Barr Virus negative (EBV-) gastric cancer patient who has had a disease progression after at least 2 prior systemic treatments for advanced or metastatic gastric cancer * Cohort 2: Checkpoint inhibitor naïve Epstein-Barr virus positive (EBV+) gastric cancer patient (as determined by standard methods, e.g. EBER ISH or LMP-1 IHC) who had at least 1 prior systemic treatment for advanced or metastatic gastric cancer * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 * Patient must have at least one measurable lesion at baseline by computed tomography(CT) or magnetic resonance imaging (MRI) * Tumor available for biopsy

Exclusion criteria

* Prior therapy with 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), any history of discontinuing from that treatment due to Grade 3 or higher immune-related adverse event (irAE) * Patient with MSI-H status * 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 clinical symptoms of active pneumonitis * Significant cardiovascular disease. New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, or chronic Grade 3 hypertension. * Significant screening electrocardiogram (ECG) abnormalities * Has had an allogenic tissue/solid organ transplant

Design outcomes

Primary

Measure	Time frame	Description
Overall Response Rate (ORR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.	The primary efficacy endpoint is Objective Response Rate (ORR) defined as the proportion of subjects whose confirmed best overall response is either Complete Response (CR) or Partial Response (PR) according to RECIST version 1.1. For the efficacy endpoints (such as ORR and DCR), frequency and percentage of subjects who have achieved a response will be summarized by cohort and 95% 2-sided confidence interval will be calculated by Clopper-Pearson method.

Secondary

Measure	Time frame	Description
Disease Control Rate (DCR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.	The Disease Control Rate (DCR) is defined as the proportion of subjects with confirmed best overall response of CR, PR or SD according to RECIST version 1.1.
Time to Response (TTR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.	The Time to Response (TTR) is defined as the time from the date of first administration of study treatment to first documented Complete Response (CR) or Partial Response (PR).
Duration of Response (DoR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.	The Duration of Response (DoR) is measured from the date of the first observation of tumor response (Complete Response (CR) or Partial Response (PR), whichever occurs first) to the date of disease progression or death for the subject with an objected response.
Progression-free Survival (PFS) in Subjects Treated With FLX475 in Combination With Pembrolizumab	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.	The Progression-free Survival (PFS) is defined as the time from the date of first administration of study treatment to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first.
Overall Survival (OS) in Subjects Treated With FLX475 in Combination With Pembrolizumab	From baseline (Cycle 1 Day 1 prior to administration of the first study dose) until death from any cause.	The Overall Survival (OS) is defined as the duration of time from the treatment start date to time to death from any cause. If subjects survive at the time of analysis, the subject will be censored at the last date of survival confirmed.

Countries

South Korea

Participant flow

Pre-assignment details

Screening will occur from Day -30 to Day -1. Once screening procedures are completed and eligibility is confirmed, subjects will be enrolled for the study and start study treatment. There is no pre-assignment planned.

Participants by arm

Arm	Count
FLX475 and Pembrolizumab Combination Therapy * Cohort 1: EBV negative / CPI naïve gastric cancer patient who has had a disease progression after at least 2 prior systemic treatments for advanced or metastatic gastric cancer * Cohort 2: EBV positive / CPI naïve gastric cancer patient (as determined by standard methods, e.g. EBER ISH or LMP-1 IHC) who had at least 1 prior systemic treatment for advanced or metastatic gastric cancer FLX475: tablet Pembrolizumab: IV infusion	20
Total	20

Arm

Count

FLX475 and Pembrolizumab Combination Therapy

* Cohort 1: EBV negative / CPI naïve gastric cancer patient who has had a disease progression after at least 2 prior systemic treatments for advanced or metastatic gastric cancer * Cohort 2: EBV positive / CPI naïve gastric cancer patient (as determined by standard methods, e.g. EBER ISH or LMP-1 IHC) who had at least 1 prior systemic treatment for advanced or metastatic gastric cancer FLX475: tablet Pembrolizumab: IV infusion

20

Total

20

Baseline characteristics

Characteristic	FLX475 and Pembrolizumab Combination Therapy
Age, Customized Cohort 1	60.0 years
Age, Customized Cohort 2	65.5 years
Age, Customized Total	64.5 years
Baseline Height (cm) Cohort 1	163.93 cm STANDARD_DEVIATION 8.94
Baseline Height (cm) Cohort 2	166.68 cm STANDARD_DEVIATION 7.51
Baseline Height (cm) Total	165.31 cm STANDARD_DEVIATION 8.16
BMI (kg/m2) Cohort 1	21.94 kg/m2 STANDARD_DEVIATION 2.75
BMI (kg/m2) Cohort 2	21.39 kg/m2 STANDARD_DEVIATION 4.72
BMI (kg/m2) Total	21.67 kg/m2 STANDARD_DEVIATION 3.77
Race/Ethnicity, Customized Cohort 1 Asian	10 Participants
Race/Ethnicity, Customized Cohort 1 Other	0 Participants
Race/Ethnicity, Customized Cohort 2 Asian	10 Participants
Race/Ethnicity, Customized Cohort 2 Other	0 Participants
Race/Ethnicity, Customized Total Asian	20 Participants
Race/Ethnicity, Customized Total Other	0 Participants
Sex: Female, Male Cohort 1 Female	3 Participants
Sex: Female, Male Cohort 1 Male	7 Participants
Sex: Female, Male Cohort 2 Female	2 Participants
Sex: Female, Male Cohort 2 Male	8 Participants
Sex: Female, Male Total Female	5 Participants
Sex: Female, Male Total Male	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	3 / 10	4 / 10
other Total, other adverse events	9 / 10	10 / 10
serious Total, serious adverse events	2 / 10	5 / 10

Outcome results

Primary

Overall Response Rate (ORR) in Subjects Treated With FLX475 in Combination With Pembrolizumab

The primary efficacy endpoint is Objective Response Rate (ORR) defined as the proportion of subjects whose confirmed best overall response is either Complete Response (CR) or Partial Response (PR) according to RECIST version 1.1. For the efficacy endpoints (such as ORR and DCR), frequency and percentage of subjects who have achieved a response will be summarized by cohort and 95% 2-sided confidence interval will be calculated by Clopper-Pearson method.

Time frame: Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.