To Evaluate the Efficacy and Safety of Tislelizumab in Combination With Lenvatinib in Participants With Selected Solid Tumors

BeiGene

Status and phase: Completed; Phase 2

Conditions: Advanced Solid Tumor

Treatments: Drug: Tislelizumab; Drug: lenvatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05014828

BGB-A317-212

CTR20211874 (Other Identifier)

Details and patient eligibility

About

This clinical trial evaluated the safety and potential benefits of combining two cancer treatments, tislelizumab and lenvatinib, in Chinese participants with advanced or metastatic cancers, including lung, head and neck, bladder, kidney, and stomach cancer. The study included two parts: the first part assessed how safe the drug combination was, and the second part examined how well it worked.

A small group of participants initially received the drugs to determine the appropriate dose, and if the treatment was well tolerated, additional participants were treated at that dose. Participants remained on the treatment unless their cancer progressed, they experienced serious side effects, or they chose to stop.

Enrollment: 58 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Participants had signed an informed consent form and were able to comply with all study requirements.

2. Participants had a histologically and/or cytologically confirmed diagnosis of advanced solid tumors, which included one of the following types:

   • Non-Small Cell Lung Cancer (NSCLC)
   • Squamous Cell Carcinoma of the Head and Neck (SCCHN)
   • Gastric Cancer (GC)
   • Urothelial Carcinoma (UC)
   • Renal Cell Carcinoma (RCC)

3. Participants had at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

4. Tumor tissue samples (approximately 10 unstained slides) were provided for central laboratory assessment of programmed death-ligand 1 (PD-L1) expression in the NSCLC cohort during the screening period. These samples were also used for retrospective exploratory biomarker analyses related to treatment response and resistance across the NSCLC, SCCHN, UC, or Gastric Cancer (GC) cohorts, in a central or designated test laboratory approved by BeiGene.

5. Participants had an Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1

Key Exclusion Criteria:

1. For participants in the NSCLC cohort, those with active leptomeningeal disease or uncontrolled, untreated brain metastases were excluded. In cohorts other than NSCLC, any participant with known leptomeningeal disease or brain metastases was excluded.
2. Participants who had received prior therapy with lenvatinib, or with antibodies targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), or any other agents specifically targeting T-cell costimulatory or immune checkpoint pathways, were excluded.
3. Participants with a history of interstitial lung disease, non-infectious pneumonitis, or any uncontrolled pulmonary conditions (including but not limited to pulmonary fibrosis or acute lung diseases) were excluded.
4. Participants who were unable to swallow capsules, or who had diseases or previous procedures that significantly affected gastrointestinal function such as malabsorption syndrome, surgical resection of the stomach or small bowel, bariatric surgery, symptomatic inflammatory bowel disease, or partial/complete bowel obstruction were excluded.
5. Participants who had experienced clinically significant bleeding (classified as Grade 2 or higher according to the Common Terminology Criteria for Adverse Events [CTCAE]) within 21 days prior to the first dose were excluded.

Note: Additional protocol-defined inclusion and exclusion criteria may have applied.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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58 participants in 6 patient groups

Safety Run In

Experimental group

Description:

Participants with advanced or metastatic unresectable solid tumors were enrolled to receive 400 mg of tislelizumab administered on Day 1 of each 6-week cycle, along with 20 mg of lenvatinib self-administered orally once daily, to determine the recommended Part 2 dose (RP2D).

Treatment:

Drug: lenvatinib

Drug: Tislelizumab

Part 2: Squamous Cell Carcinoma of the Head and Neck (SCCHN) Cohort

Experimental group

Description:

Participants with previously untreated, advanced or metastatic SCCHN received tislelizumab (400 mg administered intravenously \[IV\] every 6 weeks \[Q6W\]) in combination with lenvatinib (20 mg taken orally once daily \[QD\]) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination.

Treatment:

Drug: lenvatinib

Drug: Tislelizumab

Part 2: Renal Cell Carcinoma (RCC) Cohort

Experimental group

Description:

Systemic therapy naive participants with advanced or metastatic RCC received tislelizumab (400 mg IV Q6W) plus lenvatinib (20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination.

Treatment:

Drug: lenvatinib

Drug: Tislelizumab

Part 2: Non-Small Cell Lung Cancer (NSCLC) Cohort

Experimental group

Description:

Participants with NSCLC expressing programmed cell death-ligand 1 (PD-L1) in ≥1% of tumor cells (TC ≥1%) and who had not received prior systemic therapy received tislelizumab (400 mg IV Q6W) and lenvatinib (20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination; this cohort was closed early based on emerging external data.

Treatment:

Drug: lenvatinib

Drug: Tislelizumab

Part 2: Gastric Cancer (GC) Cohort

Experimental group

Description:

Participants with advanced GC who had received one prior line of systemic therapy were enrolled to receive tislelizumab and lenvatinib at the RP2D (tislelizumab 400 mg IV Q6W; lenvatinib 20 mg orally QD) until disease progression, start of new anticancer therapy, unacceptable toxicity, withdrawal of consent, or study termination; this cohort was closed early due to changes in the first-line standard of care.

Treatment:

Drug: lenvatinib

Drug: Tislelizumab

Part 2: Urothelial Cancer (UC) Cohort

Experimental group

Description:

Participants with cisplatin ineligible, systemic therapy naive advanced UC, were to be treated with tislelizumab (400 mg IV Q6W) and lenvatinib (20 mg orally QD). This cohort was closed prior to any participant enrollment based on emerging external data.

Treatment:

Drug: lenvatinib

Drug: Tislelizumab