Solid Tumor, AdultPhase 1/2NCT04165330
Evaluation of AL3818 in Combination With Nivolumab in Solid Tumors
A Phase 1/2 study testing AL3818 and Nivolumab Injection in people with Solid Tumor, Adult and Soft Tissue Sarcoma, run by Sarcoma Oncology Research Center, LLC at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult, Soft Tissue Sarcoma, Non Small Cell Lung Cancer
- What is being tested?
- AL3818 and Nivolumab Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2019to 31 Mar 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sarcoma Oncology Research Center
Santa Monica, California, 90403
About this study
Official title: A Phase 1/2a Evaluation of the Safety and Efficacy of Adding AL3818 (Catequentinib) to Nivolumab in Solid Tumors
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.
Read the 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.
- Conditions
- Solid Tumor, Adult, Soft Tissue Sarcoma, Non Small Cell Lung Cancer, Small Cell Lung Cancer
- Being tested
- AL3818, Nivolumab Injection
- Medical subject headings
- Sarcoma, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL3818Drug
Also called Anlotinib hydrochloride
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 InjectionDrug
Also called Opdivo
Nivolumab 240 mg Administered by injection every 2 weeks (Odd Cycles: Days 1 and 15 and Even Cycles Day 8) per 21 day Cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: AL3818; Drug: Nivolumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)
Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.
Measured: 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)
Measured: 18 months
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2019
- Study start17 Oct 2019
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Clinical Trial
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sarcoma Oncology Research Center, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Advenchen Laboratories, LLC
- Responsible party
- Sponsor
- Investigators
- Sant P Chawla, MD, Principal investigator, Sarcoma Oncology Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04165330
- Sponsor's protocol ID
- AL3818-US-005
- Status last verified
- Feb 2025
- First submitted
- 13 Nov 2019
- Last updated
- 24 Feb 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Evaluation of the Safety and Efficacy of Adding AL3818 (Catequentinib) to Nivolumab in Solid Tumors
- ClinicalTrials.gov ID
- NCT04165330
- Acronym / sponsor ID
- AL3818-US-005
- Conditions
- Solid Tumor, Adult, Soft Tissue Sarcoma, Non Small Cell Lung Cancer, Small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Sarcoma Oncology Research Center, LLCUniversity, hospital or other
- Collaborators
- Advenchen Laboratories, LLC
- Study start
- 17 Oct 2019 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 15 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Clinical Trial
| Arm | Type | Receives |
|---|---|---|
| AL3818 plus nivolumab | Experimental | Drug: AL3818, Drug: Nivolumab InjectionPart 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AL3818Also: Anlotinib hydrochlorideAL3818: 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. | Drug | AL3818 plus nivolumab |
| Nivolumab InjectionAlso: OpdivoNivolumab 240 mg Administered by injection every 2 weeks (Odd Cycles: Days 1 and 15 and Even Cycles Day 8) per 21 day Cycle. | Drug | AL3818 plus nivolumab |
Primary outcome
Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b)
Time frame: Cycle 1 (21-days)
Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.
Objective Response Rates (ORR) - Part 2 (Phase 2a)
Time frame: 18 months
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)
4 secondary outcomes
Duration of Response (DOR) - Part 2 (Phase 2a)
Time frame: 30 months
Progression Free Survival (PFS) - Part 2 (Phase 2a)
Time frame: 30 months
Overall Survival (PFS) - Part 2 (Phase 2a)
Time frame: 30 months
Clinical Benefit Rate (CBR) - Part 2 (Phase 2a)
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sant P Chawla, MD principal investigator
Sarcoma Oncology Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AL3818 and Nivolumab Injection in people with Solid Tumor, Adult and Soft Tissue Sarcoma, run by Sarcoma Oncology Research Center, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended Phase 2 Dose (RP2D) - Part 1 (Phase 1b) (time frame: Cycle 1 (21-days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.