: A Phase Ib/II Study To Evaluate Fruquintinib Monotherapy Or Plus Sintilimab In Advanced Solid Tumors

NCT03903705 | Completed Phase 1 DMC

• 1 other identifier: 2018-013-00CH3
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor

Keywords

Fruquintinib; Sintilimab; VEGFR; PD-1; Solid Tumor

Outcome Measures

Primary Outcomes (4)

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

  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.

  From first dose to 30 days post the last dose

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

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

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

  Dose expansion phase (EMC cohort): ORR by IRC

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

  Fruquintinib monotherapy arm: ORR by investigator

  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

Secondary Outcomes (7)

• 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

Other Outcomes (1)

• Exploratory outcome

  From first dose to 30 days post the last dose

Study Arms (1)

VEGFR cohort:

EXPERIMENTAL

Fruquintinib

Drug: Fruquintinib in Combination with Sintilimab

Interventions

Fruquintinib in Combination with Sintilimab DRUG

Fruquintinib plus Sintilimab: Cohort A: Fruquintinib 3 mg QD, oral dosing, 3 weeks on/1 weeks off +Sintilimab 200mg Q4W, intravenous dosing. Cohort B: Fruquintinib 4 mg QD, oral dosing, 3 weeks on/1 weeks off +Sintilimab 200mg Q4W, intravenous dosing Cohort C: Fruquintinib 5 mg QD, oral dosing, 2weeks on/1 weeks off + Sintilimab 200mg Q3W, intravenous dosing Cohort E: Fruquintinib 3 mg QD, continuous, oral dosing, + Sintilimab 200mg Q3W, intravenous dosing Fruquintinib monotherapy arm: Fruquintinib 5 mg QD, oral dosing, 3 weeks on/1 weeks off Patients will be treated until disease progression, death, unacceptable toxicity, loss of follow-up, withdrawal of consent or other conditions meet the end of treatment criteria.

Also known as: Fruquintinib

VEGFR cohort:

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Dose escalation phase: patients who have failed standard treatment (PD or intolerable toxicity after treatment), have no available standard treatment or cannot receive standard treatment (such as economic limitations);
• Dose expansion phase:
• Part 1
• Patients (HCC, renal cell carcinoma, endometrial cancer, gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, cervical cancer, NSCLC) should have PD or intolerable toxicity after 1 standard treatment, or cannot receive standard treatment (such as economic limitations or patient's wishes, etc.). Among them, requirements of standard treatment are defined as follows:
• Patients with HCC who have received 1 molecular targeted therapy (sorafenib or lenvatinib) or/and systemic chemotherapy (arsenious acid monotherapy or oxaliplatin-based combination therapy);

You may not qualify if:

• 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;
• Any live or attenuated live vaccines within 4 weeks before the first dose or planned administration during the study;
• Major surgical operation within 60 days before the first dose;
• Any surgery or invasive treatment within 4 weeks before the first dose (stable fistula formation required for fistulization for 4 weeks, except needle biopsy, venous fistula); or unhealed wounds, ulcers, fractures;
• Uncontrolled malignant pleural effusion, ascites or pericardial effusion (defined as not effectively controlled by diuretics or paracentesis, as judged by the investigator);
• Patients with hypertension uncontrolled by drugs, defined as: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 201203, China

Location

Related Publications (3)

• Wu X, Wang J, Wang D, Li G, Zhang J, Chen H, Yang H, Zhou Q, Wang K, Wu Y, Yi T, Liu J, Huang Y, Bai Y, Wang K, Jiang K, Lou H, An R, Li X, Pan Y, Wang Y, Tao W, Song K, Kang Y, Li Y, Shi W, Liu A, Yang Y, Wang Y, Chen K, Shi H, Lu P, Tan P, Fan S, Shi M, Su W. Fruquintinib plus sintilimab in patients with advanced endometrial cancer with mismatch-repair proficient status: a multicenter, single-arm, phase Ib/II trial. Nat Commun. 2025 Dec 21;17(1):658. doi: 10.1038/s41467-025-67375-3.

  PMID: 41423492 DERIVED

• Xu H, Yao X, He Z, Luo H, Li G, Guo J, Diao L, Fan Y, Li Y, Fan J, Hu X, Lu P, Shi H, Chen K, Tan P, Fan S, Shi M, Su W, Ye D. Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial. Target Oncol. 2025 Jan;20(1):113-125. doi: 10.1007/s11523-024-01120-6. Epub 2025 Jan 13.

  PMID: 39806128 DERIVED

• Guo Y, Zhang W, Ying J, Zhang Y, Pan Y, Qiu W, Fan Q, Xu Q, Ma Y, Wang G, Guo J, Su W, Fan S, Tan P, Wang Y, Luo Y, Zhou H, Li J. Phase 1b/2 trial of fruquintinib plus sintilimab in treating advanced solid tumours: The dose-escalation and metastatic colorectal cancer cohort in the dose-expansion phases. Eur J Cancer. 2023 Mar;181:26-37. doi: 10.1016/j.ejca.2022.12.004. Epub 2022 Dec 13.

  PMID: 36628898 DERIVED

MeSH Terms

Interventions

HMPL-013; sintilimab

Study Officials

• Jin Li

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-Label Phase 1b/II Study of Fruquintinib in Combination with Sintilimab to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy in Patients with Advanced Solid Tumor.

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 4, 2019
• Study Start: April 25, 2019
• Primary Completion: November 15, 2023
• Study Completion: December 16, 2024
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)