Retlirafusp Alfa Combined With Apatinib and Nab-Paclitaxel as Second-line Treatment for Gastric or Gastroesophageal Junction Cancer

Official title

Retlirafusp Alfa Combined With Apatinib and Nab-Paclitaxel as Second-line Treatment for Patients With Immunotherapy-Pretreated Gastric or Gastroesophageal Junction Cancer: A Prospective, Single-Arm Clinical Study

Overview

This is a prospective, single-arm, investigator-initiated phase II clinical study. The study evaluates the efficacy and safety of retlirafusp alfa (a PD-L1/TGF-βRII bifunctional fusion protein) combined with apatinib (a VEGFR-2 tyrosine kinase inhibitor) and nab-paclitaxel in patients with locally advanced unresectable, locally recurrent, or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma who have progressed after first-line immunotherapy-containing treatment.

Detailed description

Gastric cancer is one of the most common malignant tumors of the digestive system. For patients with advanced gastric cancer who have failed first-line immunotherapy plus chemotherapy, second-line treatment options remain limited. Retlirafusp alfa is a bifunctional fusion protein targeting PD-L1 and TGF-βRII. Apatinib is a small-molecule anti-angiogenic agent. Nab-paclitaxel is a chemotherapeutic agent recommended for second-line treatment of advanced gastric cancer. This prospective, single-arm study investigates the efficacy and safety of this triple combination regimen in immunotherapy-pretreated advanced second-line gastric or gastroesophageal junction adenocarcinoma, to provide a new therapeutic option for these patients.

Interventions

• Drug Retlirafusp alfa + Apatinib + Nab-paclitaxel
  Retlirafusp alfa: 1800 mg, intravenous infusion, day 1, every 3 weeks; until disease progression, unacceptable toxicity, or withdrawal; maximum 2 years Apatinib: 250 mg, oral, once daily; until disease progression, unacceptable toxicity, or withdrawal Nab-paclitaxel: 260 mg/m², intravenous infusion, day 1, every 3 weeks; for 4-6 cycles

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months after the last subject enrolled]

Secondary outcome measures (5)

• Disease Control Rate (DCR) [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months after the last subject enrolled]
• Progression-Free Survival (PFS) [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months after the last subject enrolled]
• Overall Survival (OS) [Time frame: From date of enrollment until the date of death from any cause, assessed up to 12 months after the last subject enrolled]
• Duration of Response (DoR) [Time frame: From first response to progression or death, up to 10 months after the last subject enrolled]
• Incidence and severity of adverse events (AEs) [Time frame: From informed consent until 30 days after last dose, assessed up to 7 months after the last subject enrolled]

Eligibility criteria

Inclusion criteria

• Able to provide written informed consent prior to any study-specific procedures
• Age ≥ 18 years
• ECOG performance status 0 or 1
• Histologically or cytologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, locally advanced unresectable, locally recurrent, or metastatic
• Human epidermal growth factor receptor 2 (HER2) negative
• Failed first-line immunotherapy-containing systemic treatment
• At least one measurable lesion per RECIST Version 1.1
• Adequate organ function:

1)Hemoglobin ≥ 90 g/L 2)Absolute neutrophil count ≥ 1.5 × 10⁹/L 3)Platelet count ≥ 80 × 10⁹/L 4)Total bilirubin < 1.5 × upper limit of normal (ULN) 5)ALT/AST < 2.5 × ULN; < 5 × ULN in patients with liver metastasis 6)Serum creatinine ≤ 1.5 × ULN or creatinine clearance > 60 mL/min 7)Urine protein < 2+ or 24-hour urine protein < 1 g 8)Left ventricular ejection fraction (LVEF) ≥ 50% 9)Coagulation function: INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN 8.Fertile male and female subjects must agree to use highly effective contraception during the study and for 6 months after the last dose of study treatment; female subjects must have a negative pregnancy test within 7 days before enrollment

Exclusion criteria

• Known hypersensitivity to any component of the study drugs
• Prior treatment with any VEGFR inhibitor (including apatinib, sorafenib, sunitinib)
• Prior treatment with retlirafusp alf
• Received any investigational drug within 4 weeks before first dose
• Received systemic corticosteroid (> 10 mg prednisone equivalent daily) or other immunosuppressive agents within 2 weeks before first dose, except for allowed topical/inhaled use or physiological replacement
• Active autoimmune disease or history of autoimmune disease (except controlled hypothyroidism, type 1 diabetes with stable insulin, vitiligo, resolved childhood asthma)
• Known immunodeficiency (including HIV infection), organ transplantation, or allogeneic hematopoietic stem cell transplantation
• Uncontrolled cardiac disease: NYHA Class ≥ II heart failure, unstable angina, myocardial infarction within 1 year, clinically significant arrhythmia requiring intervention
• Severe infection (CTCAE Grade > 2) within 4 weeks before first dose; active pulmonary infection, interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis; active tuberculosis
• Active hepatitis B (HBV DNA ≥ 2000 IU/mL) or active hepatitis C (HCV RNA positive)
• History of other malignancy within 5 years before enrollment, except adequately treated basal cell carcinoma, squamous cell carcinoma of skin, or carcinoma in situ of cervix
• Pregnant or lactating women
• Unwilling or unable to comply with study procedures
• Any other condition deemed inappropriate by the investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Henan Cancer Hospital — Zhengzhou

Identifiers

NCT: NCT07610629 · MA-GC-II-032

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗