Clinical Trials/NCT03903705

NCT03903705

Completed

Phase 1

A Phase Ib/II Study To Evaluate The Safety, Tolerability, Pharmacokinetic Profile And Preliminary Efficacy Of Fruquintinib Monotherapy Or Plus Sintilimab In Advanced Solid Tumors

Hutchmed1 site in 1 country348 target enrollmentApril 25, 2019

ConditionsAdvanced Solid Tumor

InterventionsFruquintinib in Combination with Sintilimab

DrugsFruquintinib in Combination with Sintilimab

Overview

Phase: Phase 1
Intervention: Fruquintinib in Combination with Sintilimab
Conditions: Advanced Solid Tumor
Sponsor: Hutchmed
Enrollment: 348
Locations: 1
Primary Endpoint: Dose expansion phase (except EMC cohort): efficacy outcome evaluation - ORR based on the investigator's tumor assessment
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

This is a phase Ib/II study to evaluate the safety, tolerability, PK profile and preliminary efficacy of fruquintinib monotherapy or plus sintilimab for advanced solid tumors. This study includes fruquintinib plus sintilimab treatment arm (dose escalation phase and dose expansion phase), and fruquintinib monotherapy arm.

Detailed Description

This study is composed of Fruquintinib plus sintilimab treatment arm and Fruquintinib monotherapy arm. Fruquintinib plus sintilimab treatment arm: * Dose escalation phase: it is planned to enroll about 26-39 patients * Dose expansion phase: it is planned to enroll about 309-329 patients, including about 140 patients with endometrial cancer Fruquintinib monotherapy arm: about 13 patients with advanced endometrial cancer

Registry

clinicaltrials.gov

Start Date

April 25, 2019

End Date

December 16, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Hutchmed

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have fully understood and voluntarily sign the ICF for this study (the icf must be signed before any trial-specific procedures are performed);
•Age of 18-75 years (inclusive); BMI ≥18.5 kg/m2;
•Tumor types:
•Fruquintinib plus sintilimab treatment arm
•Dose escalation phase: patients with histologically or cytologically confirmed inoperable or metastatic advanced solid tumors (including but not limited to HCC, ovarian cancer, endometrial cancer, thymic cancer, NSCLC, renal cell carcinoma);
•Dose expansion phase: histologically or cytologically confirmed inoperable metastatic advanced HCC (Barcelona Clinic Liver Cancer \[BCLC\] stage B or C), advanced renal cell carcinoma with clear cell component, advanced endometrial cancer, advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, advanced colorectal adenocarcinoma, advanced NSCLC, advanced cervical cancer, etc.;
•Fruquintinib monotherapy treatment arm: histologically or cytologically confirmed metastatic advanced endometrial cancer that cannot be surgically resected or treated with radical radiotherapy;
•In the expansion phase, patients should agree to provide tissue specimens for detection of PD-L1 expression levels and/or MSI or dMMR status;
•Requirement for prior systemic antitumor therapy:
•Fruquintinib plus sintilimab treatment arm:

Exclusion Criteria

•The AEs related to prior antitumor therapy which do not recover to ≤ CTCAE Grade 1 before the first dose, except alopecia and peripheral neurotoxicity of CTCAE Grade ≤2 caused by platinum chemotherapy;
•Patients with other malignant tumors (except cured cutaneous basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ) within 5 years before screening, only applicable to patients in expansion phase;
•Histological diagnosed fibrolamellar HCC, sarcomatoid HCC or mixed components of the above pathological types; or gastric squamous cell carcinoma or gastric adenosquamous carcinoma; or carcinosarcoma or sarcoma (endometrial cancer); or pathological diagnosis MSI-H or dMMR (endometrial cancer)
•Patients with previous or screening stage central nervous system (CNS) metastasis during screen period (for lung cancer patients with brain metastasis who have prior treatment, if there is no evidence of radiographic progression within ≥4 weeks before the first dose of study drug, and are clinically stable for ≥2 weeks after treatment, and have discontinued corticosteroids within 3 days before the first dose, the patient could be enrolled; for patients with untreated, asymptomatic lung cancer with brain metastasis \[i.e., no neurological symptoms, no need for corticosteroid or antiepileptic treatment, no brain metastasis \>1.5 cm in long diameter, no significant edema around brain metastasis\], they could be enrolled);
•Systemic antitumor therapy approved or under study within 4 weeks before the first dose, including but not limited to: chemotherapy (oral fluoropyrimidines washout period of 2 weeks), endocrine therapy, biological immunotherapy, targeted therapy (small molecule targeted therapy washout period of 2 weeks or 5 half-lives, whichever shorter), Traditional Chinese Medicine treatment (Traditional Chinese Medicine treatment with definite antitumor indications in the instructions, a 1-week washout period before the first dose is acceptable);
•Radical radiotherapy (including more than 25% bone marrow radiotherapy) within 4 weeks before the first dose;
•Brachytherapy (such as implantation of radioactive particles) within 60 days before the first dose;
•Patients previously treated with any anti-programmed cell death receptor 1 (PD-1) antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody (or any other antibody acting on T cell costimulation or checkpoint pathway) (only for the fruquintinib plus sintilimab treatment arm), or fruquintinib;
•Corticosteroids (dose \>10 mg/day prednisone or equivalent of other corticosteroids) or other immunosuppressive drugs for systemic treatment within 4 weeks before the first dose; nasal spray, inhalation or other topical use of corticosteroids (i.e., no more than 10 mg/day prednisone or equivalent of other glucocorticoids) are allowed;
•Patients with any active autoimmune disease requiring systemic treatment (i.e., use of disease remission drugs, glucocorticoids or immunosuppressive drugs) within the past 2 years; patients who only need replacement therapy (thyroid, adrenal or pituitary dysfunction with thyroid, insulin or physiological glucocorticoid replacement therapy) can be enrolled;

Arms & Interventions

VEGFR cohort:

Fruquintinib

Intervention: Fruquintinib in Combination with Sintilimab

Outcomes

Primary Outcomes

Dose expansion phase (except EMC cohort): efficacy outcome evaluation - ORR based on the investigator's tumor assessment

Time Frame: very 6 weeks since Cycle1 Day 1, and every 12 weeks after Week 48, until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent

Dose expansion phase (except endometrial cancer \[EMC\] cohort): ORR assessed by investigator

Dose escalation phase: Safety outcome evaluation - DLT, MTD/RP2D

Time Frame: From first dose to 30 days post the last dose

Dose escalation phase: To evaluate the safety and tolerability of fruquintinib plus sintilimab for advanced solid tumors in the dose escalation phase, to observe dose-limiting toxicity (DLT), the maximum tolerated dose (MTD) and/or to determine the recommended phase 2 dose (RP2D) and administration strategy of the combination therapy.

Dose expansion phase (EMC cohort): efficacy outcome evaluation - ORR based on IRC's tumor assessment

Time Frame: Every 6 weeks since Cycle1 Day 1, and every 12 weeks after Week 48, until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent

Dose expansion phase (EMC cohort): ORR by IRC

Fruquintinib monotherapy arm: efficacy outcome evaluation - ORR based on investigator's tumor assessment

Time Frame: Every 6 weeks since Cycle1 Day 1, and every 12 weeks after Week 48, until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent

Fruquintinib monotherapy arm: ORR by investigator

Secondary Outcomes

Immunogenicity Assessments for Anti-drug Antibody(ADA)(From Cycle 1, 2, 4, 6, 8, 12 (each cycle is 28 days) and the safety visit for Sintilimab until disease progression or death or new anti-cancer therapy or withdrawal of consent)
pharmacokinetics (PK) Assessments(From Cycle 1 for Fruquintinib; Cycle 1, 2, 3, 4 for Sintilimab in the dose escalation phase, and Cycle 1, 2, 4, 12 for dose expansion phase.)
Dose expansion phase (except EMC cohort): Efficacy outcome evaluation - DCR, PFS, OS, DoR, TTR based on the investigator's tumor assessment(Every 6 weeks since Cycle1 Day 1, and every 12 weeks after Week 48, until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent)
Dose expansion phase (EMC cohort): Efficacy outcome evaluation - ORR, DCR, PFS, OS, DoR, TTR based on the investigator's tumor assessment(Every 6 weeks since Cycle1 Day 1, and every 12 weeks after Week 48, until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent)
Dose expansion phase (EMC cohort): Efficacy outcome evaluation - DCR, PFS, OS, DoR, TTR based on the IRC's tumor assessment(Every 6 weeks since Cycle1 Day 1, and every 12 weeks after Week 48, until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent)
Safety outcome evaluation(From first dose to 30 days post the last dose)
Biomarker evaluation(From first dose to 30 days post the last dose)