Evaluation of AL3818 in Combination With Nivolumab in Solid Tumors

NCT04165330 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: AL3818-US-005
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor, Adult; Soft Tissue Sarcoma; Non Small Cell Lung Cancer; Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)

  Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.

  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)

  18 months

Secondary Outcomes (4)

• Duration of Response (DOR) - Part 2 (Phase 2a)

  30 months

• Progression Free Survival (PFS) - Part 2 (Phase 2a)

  30 months

• Overall Survival (PFS) - Part 2 (Phase 2a)

  30 months

• Clinical Benefit Rate (CBR) - Part 2 (Phase 2a)

  18 months

Other Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events - Parts 1 and 2

  From date of enrollment until final study visit (90 days after last treatment)

Study Arms (1)

AL3818 plus nivolumab

EXPERIMENTAL

Part 1: All participants will be assigned to receive AL3818 capsules orally, once daily at sequential deescalating doses (on treatment Days 1-14 followed by no AL3818 treatment from Days 15-21) in combination with nivolumab injection treatment (on Day 1 and Day 15) for a single 21-day cycle. Participants may continue study treatment at the AL3818 cohort dose at investigator discretion. Part 2: All participants will receive AL3818 capsules orally, once daily at the RP2D determined from Part 1 (on treatment Days 1-14 followed by no AL3818 treatment from Days 15-21) in combination with nivolumab injection treatment (every 2 weeks starting on Cycle 1, Day 1) in 21-day cycles, for up to 24 cycles of total AL3818 therapy.

Drug: AL3818; Drug: Nivolumab Injection

Interventions

AL3818 DRUG

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.

Also known as: Anlotinib hydrochloride

AL3818 plus nivolumab

Nivolumab Injection DRUG

Nivolumab 240 mg Administered by injection every 2 weeks (Odd Cycles: Days 1 and 15 and Even Cycles Day 8) per 21 day Cycle.

Also known as: Opdivo

AL3818 plus nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1: Solid tumors of all histologies, including metastatic, locally advanced, or recurrent after at least one prior line of standard therapy and requiring further treatment; OR malignant tumors for which no standard therapy exists, with or without prior therapy.
• Part 2: Histologically confirmed soft tissue sarcomas (STS), small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC), after at least one prior line of standard therapy and requiring further treatment. For STS subtypes for which no standard therapy exists, patients without prior therapy may be included.
• Measurable disease by RECIST v1.1
• Disease progression or recurrence (after treatment) within 6 months prior to enrollment
• Last dose of prior anti-cancer therapy should be performed at least 21 days prior to the first administration of study treatment.
• Life expectancy of ≥ 3 months at the time of enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Adequate baseline function within 28 days prior to enrollment:
• Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500/mm3; platelets ≥ 100,000/mm3 , Hemoglobin ≥ 9.0 g/dL.
• Renal function: Creatinine clearance (calculated by Cockcroft-Gault) must be ≥ 30 ml/min.
• Hepatic function: Bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT ≤ 3.0 × ULN.
• Coagulation profile: International normalized ratio (INR) is ≤ 2.0; absolute prothrombin time (aPTT) \< 1.5 x ULN.
• Left ventricular ejection fraction (LVEF) of \> 50% by ECHO or MUGA within 56 days prior to enrollment.
• Two blood pressure readings with systolic blood pressure \< 140 mmHg and diastolic blood pressure \< 90 mmHg at screening with 28 days prior to enrollment.
• Provide written informed consent before any study-specific procedures are initiated.

You may not qualify if:

• Major surgical procedure within 28 days or minor surgical procedure within 7 days prior to start of study treatment.
• History of prior or concurrent second primary malignancy that may interfere with the safety or efficacy assessment of the study treatment.
• Untreated, active central nervous system (CNS) metastases.
• Carcinomatous meningitis.
• Active, known, or suspected autoimmune disease or interstitial lung disease.
• Systemic treatment with corticosteroids or other immunosuppressive medications within 14 days prior to start of study treatment.
• Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to start of study treatment.
• History of untreated deep venous thrombosis (DVT) within the past 6 months.
• Presence of uncontrolled infection.
• History of Class III or IV congestive heart failure according to New York Heart Association (NYHA) classification.
• History of any of the following cardiac conditions within 6 months prior to prior to start of study treatment:
• Cardiac angioplasty or stenting, or
• Myocardial infarction, or
• Unstable angina, or
• Cerebrovascular accident.

Sponsors & Collaborators

• Sarcoma Oncology Research Center, LLC: lead
• Advenchen Laboratories, LLC: collaborator

Study Sites (1)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

MeSH Terms

Conditions

Sarcoma; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Interventions

anlotinib; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sant P Chawla, MD

  Sarcoma Oncology Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Clinical Trial

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 15, 2019
• Study Start: October 17, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: February 24, 2025

Record last verified: 2025-02

Locations

US (1)