What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC) using tyrosine kinase inhibitors (TKIs) like anlotinib can cause side effects such as hypertension, hand-foot syndrome, and diarrhea. Immune checkpoint inhibitors (ICIs) like nivolumab are associated with immune-related adverse events, including skin reactions, endocrine disorders, pneumonitis, and colitis. Combining TKIs and ICIs may increase the frequency and severity of these side effects.

What prior FDA approvals exist?

For the treatment of Small Cell Lung Cancer (SCLC), the FDA has approved several immune checkpoint inhibitors and tyrosine kinase inhibitors. Nivolumab, an immune checkpoint inhibitor targeting PD-1, has shown efficacy in SCLC, particularly in patients who have progressed after platinum-based chemotherapy. Additionally, the combination of immune checkpoint inhibitors like nivolumab with other agents, such as ipilimumab (a CTLA-4 inhibitor), has been explored. While specific tyrosine kinase inhibitors like anlotinib are still under investigation, the combination of these inhibitors with immune checkpoint inhibitors represents a promising area of research for SCLC treatment.

What other types of research exist?

Promising alternatives for SCLC patients include the combination of durvalumab (an anti-PD-L1 antibody) with chemotherapy, which has shown improved progression-free survival. Another option is atezolizumab (an anti-PD-L1 antibody) combined with chemotherapy, which has demonstrated improved overall survival in clinical trials. These combinations leverage the benefits of immune checkpoint inhibition along with the cytotoxic effects of chemotherapy.

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Tyrosine Kinase Inhibitor

AL3818 + Nivolumab for Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for Small Cell Lung Cancer (SCLC) include Tyrosine Kinase Inhibitors (TKIs) and Immune Checkpoint Inhibitors (ICIs). TKIs, such as anlotinib, block specific enzymes that signal cancer cells to grow, thereby slowing or stopping cancer progression. ICIs, like nivolumab, target proteins that cancer cells use to evade the immune system, enabling the immune system to better recognize and attack the cancer. These treatments are significant for SCLC patients as they provide targeted approaches to disrupt cancer growth and enhance immune response, potentially improving patient outcomes.

Phase 1 & 2

Waitlist Available

Led By Sant P Chawla, MD

Research Sponsored by Sarcoma Oncology Research Center, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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.

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

Must not have

Active, known, or suspected autoimmune disease or interstitial lung disease.

Carcinomatous meningitis.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 30 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called AL3818 with Opdivo to treat patients with very advanced or returning cancers. AL3818 stops blood supply to tumors, while Opdivo helps the immune system attack cancer cells.

Who is the study for?

This trial is for adults with certain advanced solid tumors, including lung cancer and sarcoma, who've had at least one previous treatment. They must have a good performance status (able to carry out daily activities), proper organ function, controlled blood pressure, no major recent surgeries or untreated brain metastases, and not be on immunosuppressants.

What is being tested?

The study tests AL3818 combined with Nivolumab in patients with advanced solid tumors. It has two parts: first to find the best dose of AL3818 when used with Nivolumab; second to check how safe and effective this combination is in treating different types of cancers like soft tissue sarcoma and lung cancer.

What are the potential side effects?

Possible side effects include high blood pressure, bleeding risks, heart issues like angina or heart attacks within the past six months. There's also a risk of immune-related problems due to Nivolumab affecting organs like lungs or intestines.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am able to care for myself and perform daily activities.

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My cancer has returned or spread and needs treatment, or there's no standard treatment for it.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any autoimmune or lung diseases.

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My cancer has spread to the lining of my brain and spinal cord.

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I have hepatitis C and haven't completed treatment, with a detectable viral load.

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I have had a blood clot in my veins that was not treated in the last 6 months.

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I have no conditions that affect my ability to take or absorb medications.

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I have HIV with a CD4+ count below 350 cells/uL.

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I have an infection that is not responding to treatment.

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I have had an organ transplant.

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I do not have active stomach ulcers or serious gut conditions, and I haven't had a gut perforation or abscess in the last month.

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I have severe heart failure.

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I have a wound, fracture, or ulcer that hasn't healed, or I have symptoms of peripheral vascular disease.

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I haven't had significant bleeding or blood clotting issues in the last 6 months.

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I have chronic hepatitis B or C with a detectable viral load.

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I haven't had major surgery in the last 28 days or minor surgery in the last 7 days.

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I have another type of cancer that could affect this study's treatment.

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I have AIDS and had an opportunistic infection in the last year.

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I have untreated brain metastases.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 30 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~30 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 30 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rates (ORR) - Part 2 (Phase 2a)

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

Secondary study objectives

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

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

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

+1 more

Other study objectives

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

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: AL3818 plus nivolumabExperimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab Injection

2017

Completed Phase 2

~410

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Small Cell Lung Cancer (SCLC) include Tyrosine Kinase Inhibitors (TKIs) and Immune Checkpoint Inhibitors (ICIs). TKIs, such as anlotinib, block specific enzymes that signal cancer cells to grow, thereby slowing or stopping cancer progression. ICIs, like nivolumab, target proteins that cancer cells use to evade the immune system, enabling the immune system to better recognize and attack the cancer. These treatments are significant for SCLC patients as they provide targeted approaches to disrupt cancer growth and enhance immune response, potentially improving patient outcomes.

Caspase-9b Interacts Directly with cIAP1 to Drive Agonist-Independent Activation of NF-κB and Lung Tumorigenesis.Trials to Overcome Drug Resistance to EGFR and ALK Targeted Therapies - Past, Present, and Future.Tailoring tyrosine kinase inhibitors to fit the lung cancer genome.