To Evaluate the Efficacy and Safety of Tislelizumab in Combination With Lenvatinib in Participants With Selected Solid Tumors
- Conditions
- Advanced Solid Tumor
- Interventions
- Registration Number
- NCT05014828
- Lead Sponsor
- BeiGene
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 58
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Participants had signed an informed consent form and were able to comply with all study requirements.
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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)
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Participants had at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
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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.
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Participants had an Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
Key
- 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.
- 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.
- 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.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Safety Run In lenvatinib 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). Safety Run In Tislelizumab 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). Part 2: Squamous Cell Carcinoma of the Head and Neck (SCCHN) Cohort lenvatinib 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. Part 2: Squamous Cell Carcinoma of the Head and Neck (SCCHN) Cohort Tislelizumab 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. Part 2: Renal Cell Carcinoma (RCC) Cohort lenvatinib 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. Part 2: Renal Cell Carcinoma (RCC) Cohort Tislelizumab 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. Part 2: Non-Small Cell Lung Cancer (NSCLC) Cohort lenvatinib 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. Part 2: Non-Small Cell Lung Cancer (NSCLC) Cohort Tislelizumab 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. Part 2: Gastric Cancer (GC) Cohort lenvatinib 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. Part 2: Gastric Cancer (GC) Cohort Tislelizumab 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. Part 2: Urothelial Cancer (UC) Cohort lenvatinib 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. Part 2: Urothelial Cancer (UC) Cohort Tislelizumab 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.
- Primary Outcome Measures
Name Time Method Safety Run-in: Number of Participants With Adverse Events (AEs) From first dose through the end of the safety run-in part, up to 124 days; The DLT observation period was 28 days after first dose. An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it is related to the study drug.
A serious adverse event (SAE) is any untoward medical occurrence that, at any dose:
* Resulted in death
* Was life-threatening
* Required hospitalization or prolongation of existing hospitalization
* Resulted in disability/incapacity
* Was a congenital anomaly/birth defect
* Was considered a significant medical AE by the investigator based on medical judgement.
A dose-limiting toxicity (DLT) was defined as a Grade 3 or 4 hematologic or nonhematologic toxicity occurring during the DLT assessment window and deemed related to one or more study drugs by the investigator.Overall Response Rate (ORR) From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months) Overall response rate is defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Tumor assessments.
CR is defined as the disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months) PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
Duration of Response (DOR) From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months) DOR was defined as the time from the first documented objective response to documented radiological disease progression as assessed by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.
Progressive disease is captured as at least a 20% increase in the sum of diameters of target lesions, using the smallest sum on study as the reference (including the baseline sum if it was the smallest). In addition to the 20% relative increase, the sum also had to show an absolute increase of at least 5 mm.Disease Control Rate (DCR) From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months) DCR was defined as the percentage of participants who demonstrated a confirmed complete response (CR), partial response (PR), or stable disease (SD) as the best overall response, in accordance with the RECIST version 1.1 criteria.
CR was defined as the disappearance of all target and non-target lesions with no new lesions observed. Any pathological lymph nodes (whether target or non-target) were required to have a reduction in short axis to less than 10 mm.
PR was defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum of diameters as the reference.
SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), using the smallest sum of diameters recorded while on study as the reference.Number of Participants Experiencing Adverse Events (AEs) From first dose of study drug to 30 days after last dose, up to the study completion date of 10 July 2024 (up to 32.5 months) An adverse event refers to any unintended or unfavorable sign, symptom, or condition (including abnormal lab results) that occurs during the study, regardless of whether it is related to the study drug.
Overall Survival (OS) From the first dose up to the primary analysis data cut-off date of 10 October 2023 (maximum time on study was 24.7 months) OS was defined as the time from randomization to the documented date of death for participants who died on or before the data cutoff date. Median OS was calculated using the Kaplan-Meier method. Data for participants who were alive at the data cutoff date were censored at their last known alive date, defined as either the clinical cutoff date for those still on treatment or the most recent available date confirming they were alive, whichever occurred first.
Trial Locations
- Locations (13)
Beijing Luhe Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Chongqing Cancer Hospital
🇨🇳Chongqing, Chongqing, China
The Peoples Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, Guangxi, China
Jiangsu Province Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Zhejiang Provincial Peoples Hospital
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Scroll for more (3 remaining)Beijing Luhe Hospital, Capital Medical University🇨🇳Beijing, Beijing, China