This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in combination with Opdivo (nivilumab) for the treatment patients with of metastatic, advanced, or recurrent solid tumors. All participants will receive open-label AL3818 with nivolumab. Part 1 consists of a dose finding phase to determine the recommended phase 2 dosage of AL3818 with nivolumab. Part 2 consists of a dose expansion phase, evaluating the safety and efficacy of the combination in patients cohorts including metastatic, advanced, or recurrent soft tissue sarcomas, non-small cell lung cancer, and small cell lung cancer.
This phase 1b/2 study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in combination with Opdivo (nivilumab) for the treatment patients with of metastatic, advanced, or recurrent solid tumors including soft tissue sarcomas (STS), non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC). All participants will receive open-label AL3818 with nivolumab on a scheduled basis. Part 1 (phase 1b) consists of a dose finding phase to determine the safety, tolerability (including recommended phase 2 dosage (RP2D), and PK profile of AL3818 given with nivolumab. Participants will receive oral AL3818 once daily on Days 1-14 and nivolumab injection on Day 1 and 15 of one 21-day cycle. Part 2 (phase 2a) consists of a dose expansion phase, to evaluate the safety and preliminary efficacy of combination treatment using AL3818 at the RP2D determined from Part 1 together with nivolumab injection at standard dosing for patients with metastatic, advanced, or recurrent STS, NSCLC, or SCLC in 21-day cycles. Oral AL3818 will be given on Days 1-14 days and nivolumab will be given every 2 weeks, for up to 24 cycles of total AL3818 therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
AL3818: Part 1 - 12 mg, 10 mg, 8 mg, or 6 mg (by dosing cohort), Part 2 - RP2D (as determined from Part 1). Administered orally once daily on Days 1-14 per 21 day Cycle.
Nivolumab 240 mg Administered by injection every 2 weeks (Odd Cycles: Days 1 and 15 and Even Cycles Day 8) per 21 day Cycle.
Sarcoma Oncology Research Center
Santa Monica, California, United States
Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)
Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.
Time frame: Cycle 1 (21-days)
Objective Response Rates (ORR) - Part 2 (Phase 2a)
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles 9 weeks after starting study treatment (C4D1) and then every 12 weeks thereafter for up to C24 cycles. ORR is measured by the number of complete (CR) and partial responses (PR)
Time frame: 18 months
Duration of Response (DOR) - Part 2 (Phase 2a)
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles 9 weeks after starting study treatment (C4D1) and then every 12 weeks thereafter for up to C24 cycles. DOR is measured as the median number of months from date of first documented objective response until first documented sign of disease progression or death due to any causes.
Time frame: 30 months
Progression Free Survival (PFS) - Part 2 (Phase 2a)
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles 9 weeks after starting study treatment (C4D1) and then every 12 weeks thereafter for up to C24 cycles. PFS is measured as the median number of months from the date of C1D1 until the first documented sign of disease progression or death due to any causes.
Time frame: 30 months
Overall Survival (PFS) - Part 2 (Phase 2a)
Evaluated by survival status beginning Cycle 1 Day 1 until last follow up on study. OS is measured as the median number of months from the date of C1D1 until death from any causes.
Time frame: 30 months
Clinical Benefit Rate (CBR) - Part 2 (Phase 2a)
Evaluated by Response Evaluation Criteria In Solid Tumors (RECIST, v1.1) criteria after three complete 21-day cycles 9 weeks after starting study treatment (C4D1) and then every 12 weeks thereafter for up to C24 cycles. CBR is measured by the number of CR, PR, and stable diseases (SD).
Time frame: 18 months
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