Safety and Efficacy of Fruquintinib Plus Nab-Paclitaxel and Iparomlimab and Tuvonralimab Injection in the Second-Line Treatment for Immunotherapy-experienced Advanced Gastric Cancer

NCT07392346 | Recruiting Phase 2

• 1 other identifier: 2026-003
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Immunotherapy has established the new standard for first-line treatment of advanced or metastatic gastric cancer. However, current second-line options-predominantly consisting of targeted therapy plus chemotherapy or chemotherapy alone-confer only modest clinical benefit. Notably, pivotal phase III second-line trials (REGARD, RAINBOW, RAINBOW-Asia, FRUTIGA) exclusively enrolled patients who progressed on chemotherapy regimens; thus, high-quality evidence guiding second-line treatment specifically for immunotherapy-refractory patients remains scarce, representing a significant unmet medical need. Anti-angiogenic agents have demonstrated capacity to ameliorate the hypoxic, immunosuppressive tumor microenvironment while exerting synergistic anti-tumor effects when combined with immune checkpoint inhibitors. Exploratory studies evaluating immunotherapy combined with anti-angiogenic therapy plus chemotherapy in advanced gastric cancer patients after first-line failure have yielded encouraging efficacy signals (NCT03966118, NCT04982276), with objective response rates of 30-40% and median progression-free survival approaching 6 months. Based on this, the investigators aim to evaluate the efficacy and safety profile of fruquintinib combined with nab-paclitaxel and Iparomlimab and Tuvonralimab Injection (a novel bispecific antibody) as second-line treatment for patients with advanced gastric cancer who have experienced disease progression during or after first-line immunotherapy-containing regimens.

Conditions

Gastric Cancer Adenocarcinoma Metastatic

Outcome Measures

Primary Outcomes (1)

• Progress-free Survival(PFS)

  The time from enrollment until tumor progression or death from any cause, whichever occurred first

  24 months

Secondary Outcomes (3)

• Objective response rate (ORR)

  24 months

• Disease control rate (DCR)

  24 months

• Overall Survival (OS)

  24 months

Study Arms (1)

Study arm

EXPERIMENTAL

Fruquintinib Plus Nab-Paclitaxel and Iparomlimab and Tuvonralimab Injection are administered until disease progression or toxicity intolerable.

Drug: Fruquintinib; Drug: Iparomlimab and Tuvonralimab; Drug: Paclitaxel (albumin-bound)

Interventions

Paclitaxel (albumin-bound) DRUG

250 mg/m², Day 1, q3W

Study arm

Fruquintinib DRUG

3 mg qd, po, q3W; After 6 cycles of combination therapy, maintenance treatment consisting of Iparomlimab and Tuvonralimab Injection plus Fruquintinib will continue until disease progression, intolerable toxicity, initiation of new antitumor therapy, withdrawal of informed consent, or investigator's determination that the subject should discontinue from study treatment.

Study arm

Iparomlimab and Tuvonralimab DRUG

5.0 mg/kg, Day 1, q3W, iv. After 6 cycles of combination therapy, maintenance treatment consisting of Iparomlimab and Tuvonralimab Injection plus Fruquintinib will continue until disease progression, intolerable toxicity, initiation of new antitumor therapy, withdrawal of informed consent, or investigator's determination that the subject should discontinue from study treatment.

Study arm

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years
• Pathologically or cytologically confirmed diagnosis of gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.
• Failure of first-line treatment with PD-1/PD-L1 inhibitors
• With measurable lesions according to RECIST 1.1 criteria.
• ECOG performance status of 0-1
• Expected survival ≥3 months;
• Major organ functions meet the following requirements :
• Absolute neutrophil count (ANC) ≥ 1,500/mm³ (1.5 × 10⁹/L) (no growth factors used within 14 days).
• Platelet count (PLT) ≥ 100,000/mm³ (100 × 10⁹/L) (no correction therapy used within 7 days).
• Hemoglobin (Hb) ≥ 9 g/dL (90 g/L) (no correction therapy used within 7 days).
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN).
• Total bilirubin (BIL) ≤ 1.5 × upper limit of normal (ULN).
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) levels ≤ 2.5 × upper limit of normal (ULN); ≤ 5 × upper limit of normal (ULN) for patients with liver metastases.
• Urinalysis is normal, or urine protein \< (++), or 24-hour urine protein level \< 1.0 g.
• Normal coagulation function, with no history of active bleeding or thrombotic diseases:

You may not qualify if:

• History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of study medication.
• Uncontrolled pleural, pericardial, or peritoneal effusions requiring repeated drainage.
• Hypersensitivity to any component of monoclonal antibodies, fruquintinib, or albumin-bound paclitaxel.
• Receipt of any of the following treatments:
• Severe adverse reactions to prior immunotherapy.
• Prior treatment with CTLA4 inhibitors.
• Any study medication within 4 weeks prior to the first dose of study medication.
• Concurrent enrollment in another clinical study (excluding observational studies or survival follow-ups of interventional studies).
• Last dose of anti-cancer therapy ≤ 3 weeks prior to the first study medication, or fixed-field palliative radiotherapy ≤ 2 weeks prior to study intervention.
• Corticosteroid use (\>10 mg prednisone equivalent/day) within 2 weeks prior to study medication; the investigator may decide on eligibility in special cases. Inhaled/topical steroids and adrenal replacement at \>10 mg/day prednisone equivalent are permitted in the absence of active autoimmune diseases.
• Anti-tumor vaccines or live vaccines within 4 weeks prior to study medication.
• Major surgery or severe trauma within 4 weeks prior to study medication.
• Central nervous system metastases.
• History of active autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism) or a history of such diseases (excluding vitiligo, or childhood asthma/allergies cured and requiring no intervention in adulthood; autoimmune hypothyroidism on stable thyroid replacement; type 1 diabetes on stable insulin).
• Immunodeficiency history (including HIV-positive status, acquired/congenital immunodeficiency, organ transplantation, or allogeneic bone marrow transplantation).

Sponsors & Collaborators

• Dai, Guanghai: lead

Study Sites (1)

Chinese PLA General Hospital, Beijing

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Interventions

HMPL-013; Taxes

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor,Chief Physician

Study Record Dates

• First Submitted: January 30, 2026
• First Posted: February 6, 2026
• Study Start: December 1, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2028
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

CN (1)