Study of Tislelizumab in Participants With Resectable Esophageal Squamous Cell Carcinoma (RATIONALE-213)

BeiGene

Status and phase: Completed; Phase 2

Conditions: Resectable Esophageal Squamous Cell Carcinoma

Treatments: Procedure: Surgical resection; Drug: 5-fluorouracil; Radiation: Radiotherapy; Drug: Paclitaxel; Drug: Cisplatin; Drug: Tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04974047

BGB-A317-213

CTR20211753 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the pathological complete response (pCR) in participants receiving tislelizumab plus chemotherapy/chemoradiotherapy as neoadjuvant treatment.

Full description

This study enrolled participants with esophageal squamous cell carcinoma who were eligible to have their tumor removed by surgery (also called surgical resection). The treatment phase of the study included the following:

• Induction therapy, in which participants received 1 cycle of chemotherapy;

• Neoadjuvant therapy (neoadjuvant refers to treatment that occurs before surgery, which can make the tumor easier to remove). In this study participants received neoadjuvant therapy based on their response to induction therapy. Response to induction therapy was assessed using the maximum standardized uptake value (SUVmax) measured using a Positron Emission Tomography (PET) scan. The SUV number refers to the level of brightness on the PET scan which reflects metabolic activity; increased metabolic activity can indicate cancerous growth.

  • Participants with a decrease in SUVmax of 35% or more after induction therapy received neoadjuvant treatment with tislelizumab plus chemotherapy.
  • Participants with a decrease in SUVmax less than 35% after induction therapy received neoadjuvant treatment with tislelizumab plus chemotherapy and radiotherapy.

• Surgery to remove the remaining tumor (resection) was to occur 4-6 weeks after completion of neoadjuvant treatment.

After surgery participants were followed until death, lost to follow-up, withdrawal of consent, or until the study was completed

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Histologically confirmed esophageal squamous cell carcinoma (ESCC).
• Stage cT1-2N+M0 and cT3NanyM0 (per The American Joint Committee on Cancer 8th Edition).
• Evaluation by the investigator to confirm eligibility for an R0 resection with curative intent.
• Adequate hematologic and organ function, defined by protocol-specified laboratory test results obtained within 14 days before first dose.

Key Exclusion Criteria:

• Ineligible for treatment with any of the chemotherapy doublets of protocol-specified chemotherapy.

• Any prior therapy for current ESCC, including investigational agents, chemotherapy, radiotherapy, targeted therapy agents, or prior therapy with an anti-programmed cell death protein-1, anti-programmed cell death protein ligand-1, anti-programmed cell death protein ligand-2, or any other antibody or drug specifically targeting T-Cell co-stimulation or checkpoint pathways.

• History of fistula due to primary tumor invasion.

• Participants with high risk of fistula or sign of perforation evaluated by investigator.

• Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days before first dose.

  * Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) and topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption, and short course (≤ 7 days) of corticosteroid prescribed prophylactically or for the treatment of a non-autoimmune condition are permitted.

• Active autoimmune diseases or history of autoimmune diseases that may relapse.

  * Controlled Type I diabetes, hypothyroidism only requiring hormone replacement, controlled celiac disease, skin diseases (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases.

• With infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection.

  • Severe infections within 4 weeks before first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Receive therapeutic oral or intravenous antibiotics within 2 weeks before first dose.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Cohort A (Responder)

Experimental group

Description:

Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in positron emission tomography (PET) Standardized Uptake Value (SUV)max ≥ 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and chemotherapy doublet (cisplatin + paclitaxel) for 2 cycles. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.

Treatment:

Drug: Tislelizumab

Drug: Cisplatin

Drug: Paclitaxel

Procedure: Surgical resection

Cohort B (Non-responder)

Experimental group

Description:

Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax \< 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.

Treatment:

Drug: Tislelizumab

Drug: Cisplatin

Drug: Paclitaxel

Radiation: Radiotherapy

Drug: 5-fluorouracil

Procedure: Surgical resection