Tislelizumab Combined With Chemotherapy Versus Chemotherapy Alone in Recurrent or Metastatic Nasopharyngeal Cancer (NPC) (RATIONALE-309)

BeiGene

Status and phase: Completed; Phase 3

Conditions: Recurrent or Metastatic Nasopharyngeal Cancer

Treatments: Drug: Placebo; Drug: Gemcitabine; Drug: Tislelizumab; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03924986

CTR20182534 (Registry Identifier)

BGB-A317-309

Details and patient eligibility

About

This study was designed to compare the efficacy and safety of tislelizumab (BGB-A317) combined with gemcitabine plus cisplatin versus placebo combined with gemcitabine plus cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal cancer.

Enrollment: 263 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
2. Aged between 18 to 75 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place)
3. Histologically or cytologically confirmed, recurrent or metastatic NPC
4. Participants must be able to provide fresh or archival tumor tissues (formalin-fixed paraffin-embedded [FFPE] blocks or approximately 10 [≥ 6] freshly cut unstained FFPE slides) with an associated pathological report. The archival tumor tissues must be collected within 2 years before screening. In the absence of sufficient archival tumor tissues, a fresh biopsy of a tumor lesion at baseline is mandatory
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
6. Must have ≥ 1 measurable lesions as defined per RECIST v1.1
7. Must be treatment-naive for recurrent or metastatic NPC.

Key Exclusion Criteria:

1. Participants with locally recurrence suitable for curative surgery or radiotherapy

2. Received any approved systemic anticancer therapy, including hormonal therapy, within 28 days prior to initiation of study treatment. The following exception is allowed:

   • Palliative radiotherapy for bone metastases or soft tissue lesions should be completed > 7 days prior to baseline imaging.

3. Has received any immunotherapy (including but not limited to interferons, interleukin 2, tumor necrosis factor interleukin, and thymoxin) or any investigational therapies within 14 days or 5 half-lives (whichever is longer) of randomization

4. Received prior therapies targeting programmed cell death protein-1 (PD-1) or programmed cell death protein ligand-1 (PD-L1)

5. Active leptomeningeal disease or uncontrolled, untreated brain metastasis

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

7. Any active malignancy ≤ 2 years before randomization except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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263 participants in 2 patient groups, including a placebo group

Arm A: Tislelizumab + Gemcitabine + Cisplatin

Experimental group

Description:

Participants received tislelizumab 200 mg intravenously (IV) once every 3 weeks (Q3W), gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have continued to receive tislelizumab monotherapy.

Treatment:

Drug: Cisplatin

Drug: Tislelizumab

Drug: Gemcitabine

Arm B: Placebo + Gemcitabine + Cisplatin

Placebo Comparator group

Description:

Participants received placebo IV once every 3 weeks, gemcitabine 1 g/m\^2 IV on days 1 and 8 of each 21-day cycle and cisplatin 80 mg/m\^2 IV on day 1 of each cycle for 4 to 6 treatment cycles. Participants may have received treatment for longer at the Investigator's discretion until disease progression. Participants with confirmed disease progression may have crossed over to receive tislelizumab 200 mg IV Q3W monotherapy.

Treatment:

Drug: Cisplatin

Drug: Gemcitabine

Drug: Placebo