Sonidegib and Pembrolizumab in Treating Patients With Advanced Solid Tumors

NCT04007744 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: MC1718NCI-2019-0409818-007218
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the best dose of sonidegib when given together with pembrolizumab and to see how well they work in treating patients with solid tumor that has spread to other places in the body (advanced). Sonidegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sonidegib and pembrolizumab may work better than standard treatment in treating patients with advanced solid tumors.

Conditions

Metastatic Gastric Adenocarcinoma; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Gastric Cancer AJCC v8; Locally Advanced Gastroesophageal Junction Adenocarcinoma; Locally Advanced Urothelial Carcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Melanoma; Refractory Lung Non-Small Cell Carcinoma; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8; Stage IV Lung Cancer AJCC v8; Unresectable Malignant Solid Neoplasm; Unresectable Melanoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Locally Advanced Gastric Adenocarcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Urothelial Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

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

  MTD is defined as the dose level below the lowest dose that induces dose- limiting toxicity (DLT) in at least one-third of patients. Three patients will be treated at a given dose level combination and observed for at least 21 days from start of treatment to assess toxicity.

  Up to 21 days

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

  Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

  Up to 30 days post treatment

Secondary Outcomes (6)

• Incidence of adverse events

  Up to 30 days post treatment

• Response profile

  Up to 30 days post treatment

• Duration of response (DOR)

  From the date on which an objective response is first determined until the first date on which radiographic disease progression is determined, assessed up to 30 days

• Disease control rate (DCR)

  At 6 months

• Overall survival (OS)

  Up to 30 days post treatment

Other Outcomes (3)

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

  Baseline up to 30 days post treatment

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

  At baseline

• Level of serum soluble PDL-1

  At baseline

Study Arms (1)

Treatment (sonidegib, pembrolizumab)

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: Sonidegib

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (sonidegib, pembrolizumab)

Sonidegib DRUG

Given PO

Also known as: Erismodegib, LDE-225, LDE225, Odomzo, Smoothened Antagonist LDE225

Treatment (sonidegib, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Measurable disease by RECIST criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Hemoglobin \>= 9.0 g/dL (obtained =\< 28 days prior to registration).
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 28 days prior to registration).
• Platelet count \>= 100,000/mm\^3 (obtained =\< 28 days prior to registration).
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN (obtained =\< 28 days prior to registration).
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement) (obtained =\< 28 days prior to registration).
• Creatinine phosphokinase (CK) =\< 2.5 x ULN (obtained =\< 28 days prior to registration).
• Serum creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 ml/min using the Cockcroft-Gault formula (obtained =\< 28 days prior to registration).
• Negative serum pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only.
• Patients of childbearing potential agree to use two forms of medically approved contraception while taking the study drug and for 20 months following the last dose of study drug. Patients with partners of childbearing potential agree to use condoms, even after vasectomy, to avoid potential drug exposure to partner during study drug and for 8 months following the last dose of study drug.
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).
• Willing to provide blood samples for correlative research purposes.
• Must be able to swallow capsules and have no significant impairment in gastrointestinal absorption.

You may not qualify if:

• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant persons.
• Nursing persons.
• Persons of childbearing potential and with partners of childbearing potential who are unwilling to employ adequate contraception.
• CTCAE \>= grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids, or permanent treatment discontinuation due to toxicity.
• Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or a history of rhabdomyolysis.
• Concomitant treatment with drugs that are recognized to cause rhabdomyolysis, including statins.
• NOTE: Patients taking such medications need to be discontinued at least 2 weeks prior to starting sonidegib treatment. If an agent to control lipids is required, pravastatin may be given with caution.
• Receiving strong inhibitors or inducers of CYP3A4/5, moderate inducers of CYP3A4, and/or grapefruit/grapefruit juice or starfruit products that cannot be discontinued before starting treatment with sonidegib.
• NOTE: Medications that are strong CYP3A4/5 inhibitors or inducers, moderate inducers of CYP3A4, and grapefruit/grapefruit juice/starfruit products should be discontinued at least 4 weeks prior to starting treatment with sonidegib.
• Active autoimmune diseases that have required systemic treatment modifications within the past 3 months or that require chronic systemic steroids or immunosuppressive agents.
• Requirement for systemic corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\< 14 days prior to registration.
• NOTE: Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Life expectancy \< 3 months.
• Central nervous system metastases that are untreated, symptomatic, or require steroids.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Melanoma; Carcinoma, Transitional Cell; Lung Neoplasms

Interventions

pembrolizumab; sonidegib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Mojun Zhu, M.D.

  Mayo Clinic in Rochester

  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

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 5, 2019
• Study Start: February 13, 2020
• Primary Completion: May 8, 2025
• Study Completion (Estimated): July 2, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

US (3)