Clinical Trials /

Evaluation of AL3818 in Combination With Nivolumab in Solid Tumors

NCT04165330

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Small Cell Lung Carcinoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of AL3818 in Combination With Nivolumab in Solid Tumors
  • Official Title: A Phase 1/2a Evaluation of the Safety and Efficacy of Adding AL3818 (Catequentinib) to Nivolumab in Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: AL3818-US-005
  • NCT ID: NCT04165330

Conditions

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

Interventions

DrugSynonymsArms
AL3818Anlotinib hydrochlorideAL3818 plus nivolumab
Nivolumab InjectionOpdivoAL3818 plus nivolumab

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
AL3818 plus nivolumabExperimentalPart 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.
  • AL3818
  • Nivolumab Injection

Eligibility Criteria

        Key Inclusion Criteria:

          -  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:

               1. Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500/mm3; platelets ≥
                  100,000/mm3 , Hemoglobin ≥ 9.0 g/dL.

               2. Renal function: Creatinine clearance (calculated by Cockcroft-Gault) must be ≥ 30
                  ml/min.

               3. 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.

               4. 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.

        Key Exclusion Criteria:

          -  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:

               1. Cardiac angioplasty or stenting, or

               2. Myocardial infarction, or

               3. Unstable angina, or

               4. Cerebrovascular accident.

          -  Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic
             peripheral vascular disease.

          -  Evidence of bleeding diathesis or coagulopathy or clinically significant bleeding such
             as gross hematuria, gastrointestinal bleeding and hemoptysis within 6 months prior to
             start of study treatment.

          -  QTcF > 470 msec (per Fridericia's formula) on electrocardiogram within 28 prior to
             start of study treatment.

          -  Concurrent human Immunodeficiency virus (HIV) infection with CD4+ count < 350
             cells/uL.

          -  Known history of acquired immunodeficiency syndrome (AIDS) and an opportunistic
             infection within the past 12 months.

          -  Serologic evidence of chronic hepatitis B virus (HBV) via positive hepatitis B virus
             surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid (HCV antibody) with a
             viral load above the limit of quantification.

          -  History of hepatitis C virus (HCV) infection without completion of curative antiviral
             treatment with a viral load above the limit of quantification.

          -  History of organ transplantation.

          -  Clinical conditions affecting the intake or absorption of AL3818 (e.g., inability to
             swallow, chronic diarrhea, intestinal obstruction, malabsorption disease, stomach or
             small bowel resection).

          -  Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a
             history of any significant drug allergy (e.g., anaphylaxis, hepatotoxicity,
             immune-mediated thrombocytopenia or anemia.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)
Time Frame:Cycle 1 (21-days)
Safety Issue:
Description:Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.

Secondary Outcome Measures

Measure:Duration of Response (DOR) - Part 2 (Phase 2a)
Time Frame:30 months
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS) - Part 2 (Phase 2a)
Time Frame:30 months
Safety Issue:
Description: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.
Measure:Overall Survival (PFS) - Part 2 (Phase 2a)
Time Frame:30 months
Safety Issue:
Description: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.
Measure:Clinical Benefit Rate (CBR) - Part 2 (Phase 2a)
Time Frame:18 months
Safety Issue:
Description: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).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sarcoma Oncology Research Center, LLC

Last Updated

November 15, 2019