Tislelizumab in Combination With Pre-operative CRT Versus SOC for Locally Advanced G/GEJ Adenocarcinoma

Nanjing University

Status and phase: Enrolling; Phase 2

Conditions: Gastric Cancer; Gastroesophageal-junction Cancer

Treatments: Drug: S-1; Radiation: Radiation; Drug: Oxaliplatin; Drug: Nab paclitaxel; Drug: Tislelizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT05687357

BGB-A317-2010-IIT

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy of Tislelizumab in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma.

The primary study hypotheses are that:

Neoadjuvant and adjuvant Tislelizumab plus chemoradiotherapy, followed by adjuvant Tislelizumab and chemotherapy is superior to neoadjuvant chemoradiotherapy or chemotherapy, followed by adjuvant chemotherapy in terms of rate of Pathological Complete Response (pathCR) at the time of surgery.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3~4aN+M0 or T4bNanyM0 （AJCC Version 8）
2. Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1
3. Has adequate organ function.
4. Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.
5. Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.

Exclusion criteria

1. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
2. Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
3. Has an active infection requiring systemic therapy.
4. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
5. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment.
7. Has an active autoimmune disease that has required systemic treatment in past 2 years.
8. Has a known history of human immunodeficiency virus (HIV) infection.
9. Has a known history of Hepatitis B or known active Hepatitis C virus infection (HBsAg positive with HBV DNA≥500 IU/ml；HCV：HCV antigen positive with HCV copies >ULN).
10. Has had an allogenic tissue/solid organ transplant.
11. Has received a live vaccine within 30 days prior to the first dose of study treatment.
12. Female participants who are breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 3 patient groups

Arm A: Tislelizumab + Chemoradiotherapy

Experimental group

Description:

Neoadjuvant: Prior to surgery, participants receive 4 cycles of Tislelizumab 200 mg via intravenous (IV) infusion on C1D1, C2D1, C2D22, C3D1 PLUS radiotherapy (TOMO or VMAT) 45Gy/1.5f PLUS S-1 initial dose depends on the body surface area, PO, bid, C1D1\~D14，C2D1\~C2D5, C2D8\~C2D12, C2D15\~C2D19, C2D22\~C2D26, C2D29\~C2D33, C3D1\~D14 and oxaliplatin 130mg/m\^2, IV, C1D1 and C3D1 OR S-1 initial dose depends on the body surface area, PO, bid, C1D1\~D14，C3D1\~D14 and nab-paclitaxel, IV 100\~120mg/m\^2，IV，C1D1，C1D8，C2D1，C2D8，C2D16，C2D22，C3D1 and C3D8. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1, AND up to 16 cycles of Tislelizumab 200 mg via IV infusion on Day 1 Q3W.

Treatment:

Drug: S-1

Radiation: Radiation

Drug: Nab paclitaxel

Drug: Tislelizumab

Drug: Oxaliplatin

Arm B: Chemoradiotherapy

Active Comparator group

Description:

Neoadjuvant: Prior to surgery, participants receive radiotherapy (TOMO or VMAT) 45Gy/1.5f PLUS S-1 initial dose depends on the body surface area, PO, bid, C1D1\~D14，C2D1\~C2D5, C2D8\~C2D12, C2D15\~C2D19, C2D22\~C2D26, C2D29\~C2D33, C3D1\~D14 and oxaliplatin 130mg/m\^2, IV, C1D1 and C3D1 OR S-1 initial dose depends on the body surface area, PO, bid, C1D1\~D14，C3D1\~D14 and nab-paclitaxel, IV 100\~120mg/m\^2，IV，C1D1，C1D8，C2D1，C2D8，C2D16，C2D22，C3D1 and C3D8. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1.

Treatment:

Drug: S-1

Radiation: Radiation

Drug: Nab paclitaxel

Drug: Oxaliplatin

Arm C: Chemotherapy

Active Comparator group

Description:

Neoadjuvant: S-1 initial dose depends on the body surface area, PO, bid, D1\~D14，Q 3W for 6 cycles, and oxaliplatin 130mg/m\^2, IV, D1 of each cycle for 6 cycles OR nab-paclitaxel, IV 100\~120mg/m\^2，IV，D1 and D8 for each cycle for 6 cycles. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of SOX OR S-1 and nab-paclitaxel AND 3 cycles of S-1.

Treatment:

Drug: S-1

Drug: Nab paclitaxel

Drug: Oxaliplatin