What side effects are associated with this type of intervention?

Common treatments for cutaneous melanoma, such as Hedgehog pathway inhibitors (e.g., Sonidegib) and PD-1 inhibitors (e.g., Pembrolizumab), have distinct side effect profiles. Hedgehog pathway inhibitors can cause muscle spasms, hair loss, altered taste, fatigue, and gastrointestinal issues like nausea and diarrhea. PD-1 inhibitors, on the other hand, are associated with immune-related adverse effects, including dermatitis, colitis, hepatitis, endocrinopathies, and pneumonitis. Both treatments require careful monitoring due to their potential for significant side effects.

What prior FDA approvals exist?

For the treatment of Cutaneous Melanoma, the FDA has approved several PD-1 inhibitors, including Pembrolizumab (Keytruda) and Nivolumab (Opdivo). These drugs work by blocking the PD-1 pathway, thereby enhancing the immune system's ability to fight cancer. While Hedgehog Pathway Inhibitors like Sonidegib are primarily used for basal cell carcinoma, they are not typically used for Cutaneous Melanoma. Therefore, the focus for melanoma treatment has been more on immunotherapy agents like PD-1 inhibitors.

What other types of research exist?

Promising novel alternatives for Cutaneous Melanoma treatment in 2024 include: 1) LAG-3 inhibitors such as Relatlimab, which have shown efficacy in combination with PD-1 inhibitors. 2) TIL (Tumor-Infiltrating Lymphocyte) therapy, which involves expanding a patient's own immune cells to fight cancer. 3) BRAF/MEK inhibitors for patients with specific genetic mutations. These alternatives offer new mechanisms of action and potential benefits for melanoma patients.

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Checkpoint Inhibitor

Sonidegib + Pembrolizumab for Advanced Cancers

Phase 1

Recruiting

Led By Mojun Zhu, M.D.

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

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

Must have

Pathologically confirmed recurrent or metastatic HNSCC

Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

Must not have

Active autoimmune diseases that have required systemic treatment modifications within the past 3 months or that require chronic systemic steroids or immunosuppressive agents

CTCAE >= grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids, or permanent treatment discontinuation due to toxicity

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 6 months

Awards & highlights

No Placebo-Only Group

Approved for 5 Other Conditions

All Individual Drugs Already Approved

Summary

This trial tests the best dose of sonidegib combined with pembrolizumab for treating advanced solid tumors. Sonidegib blocks enzymes needed for tumor growth, while pembrolizumab helps the immune system attack cancer. The study focuses on patients with advanced cancers that have spread, aiming to find a more effective treatment than standard options.

Who is the study for?

Adults with advanced solid tumors, including various cancers like melanoma and lung cancer, who have tried other treatments without success. They must be in good physical condition (ECOG 0 or 1), have measurable disease, and agree to use two forms of contraception if of childbearing potential. Not eligible if pregnant, nursing, expected to live less than three months, or unable to take the study drug due to certain health conditions.

What is being tested?

The trial is testing the combination of Sonidegib and Pembrolizumab for treating advanced solid tumors. It aims to find the best dose of Sonidegib that works well with Pembrolizumab—an antibody therapy—to potentially stop tumor growth by blocking enzymes needed for cell growth while helping the immune system attack cancer.

What are the potential side effects?

Possible side effects include reactions related to immune system activation which may affect organs, fatigue, digestive issues and muscle-related problems such as inflammation or rhabdomyolysis—a serious syndrome resulting from direct or indirect muscle injury.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has returned or spread and is confirmed by tests.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I can swallow pills and my stomach absorbs medications well.

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My cancer has worsened after treatment with platinum-based chemotherapy.

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I have EGFR, ALK, or BRAF mutations and my cancer progressed after FDA-approved treatments.

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My head/neck cancer returned or spread after treatment with platinum-based chemotherapy.

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My tumor is advanced or has spread and tests positive for PD-L1.

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My condition worsened after at least one treatment.

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My melanoma cannot be removed by surgery or has spread.

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My colorectal cancer has worsened despite treatment with standard therapies.

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I have squamous cell cancer in my head or neck.

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I am 18 years old or older.

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My condition worsened after two or more treatments.

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I am fully active or can carry out light work.

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My cancer is in the stomach or where the stomach meets the esophagus.

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My cancer cannot be surgically removed, has spread, and is either MSI-H or mismatch repair deficient.

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My cancer got worse within a year of platinum-based treatment.

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My cancer is identified as MSI-H.

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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My cancer is advanced or has spread and is in the urinary system.

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I have been newly diagnosed and cannot receive cisplatin.

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My lung cancer has spread and is confirmed by tests.

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I have EGFR, ALK, or BRAF mutations and my cancer progressed after FDA-approved treatments.

Exclusion Criteria

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

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I have an autoimmune disease needing regular immune system medications.

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I had a severe reaction to previous immunotherapy that needed steroids or stopped treatment.

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I have brain metastases that are either untreated, causing symptoms, or need steroids.

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I have not received a live vaccine in the last 30 days.

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I have a neuromuscular disorder or a history of severe muscle breakdown.

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I am not taking medications known to cause severe muscle damage, like statins.

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I am not taking any strong drugs that affect liver enzymes or consuming grapefruit/starfruit products.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 6 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

Maximum tolerated dose (MTD) of sonidegib in combination with pembrolizumab (Part A)

Response rate of sonidegib in combination with pembrolizumab (Part B)

Secondary study objectives

Disease control rate (DCR)

Duration of response (DOR)

Incidence of adverse events

+3 more

Other study objectives

Changes in immune cell markers, cytokines, and soluble PD-L1

Level of serum soluble PDL-1

Levels of Bcl-2 interacting mediator of cell death (BIM)

Side effects data

From 2021 Phase 2 trial • 28 Patients • NCT02086552

93%

Fatigue

85%

Neutrophil count decreased

74%

Peripheral sensory neuropathy

74%

Diarrhea

70%

Myalgia

70%

White blood cell decreased

67%

Platelet count decreased

52%

Rash maculo-papular

44%

Dysgeusia

37%

Vomiting

37%

Constipation

19%

Alopecia

19%

Lymphocyte count decreased

19%

Weight loss

15%

Musculoskeletal and connective tissue disorder - Other, specify

11%

Anemia

11%

Anorexia

11%

Skin and subcutaneous tissue disorders - Other, specify

Infections and infestations - Other, specify

Hot flashes

Thromboembolic event

Tinnitus

Alkaline phosphatase increased

Arthralgia

Hematuria

Sinusitis

Lung infection

Syncope

Acute kidney injury

Corneal infection

Cough

Dry skin

Nausea

Blurred vision

Hypertension

Febrile neutropenia

Alanine aminotransferase increased

CPK increased

Dehydration

Abdominal pain

Gastritis

Bladder infection

Headache

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Sonidegib, Lenalidomide)

Awards & Highlights

No Placebo-Only Group

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

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (sonidegib, pembrolizumab)Experimental Treatment2 Interventions

Patients receive sonidegib PO QD on days 1-8, and pembrolizumab IV over 30 minutes on day 8. Treatment repeats every 21 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sonidegib

FDA approved

Pembrolizumab

FDA approved

0 / 30Eligibility 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 Cutaneous Melanoma include Hedgehog Pathway Inhibitors and PD-1 Inhibitors. Hedgehog Pathway Inhibitors, such as Sonidegib, work by blocking the Hedgehog signaling pathway, which is crucial for the growth and survival of cancer cells. This inhibition can reduce tumor growth and spread. PD-1 Inhibitors, like Pembrolizumab, enhance the immune system's ability to detect and destroy cancer cells by blocking the PD-1 protein on immune cells, which cancer cells often exploit to avoid immune attack. These treatments are significant for Cutaneous Melanoma patients as they offer targeted approaches that can lead to more effective and durable responses compared to traditional therapies.