Sonidegib + Pembrolizumab for Advanced Cancers
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: Mayo Clinic
Must not be taking: Statins, CYP3A4 inhibitors
Disqualifiers: Pregnancy, Neuromuscular disorders, Autoimmune diseases, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications before starting treatment. If you are on drugs that cause muscle damage (like some statins) or affect liver enzymes (CYP3A4/5 inhibitors or inducers), you need to stop them at least 2 to 4 weeks before starting the trial. If you need a medication to control cholesterol, pravastatin may be used with caution.
What data supports the effectiveness of the drug Sonidegib + Pembrolizumab for Advanced Cancers?
Pembrolizumab, one of the drugs in the treatment, has shown effectiveness in improving survival and response rates in various cancers, such as non-small-cell lung cancer and melanoma, by helping the immune system attack cancer cells more effectively.
12345What safety information is available for the combination of Sonidegib and Pembrolizumab in humans?
Pembrolizumab (Keytruda) has been associated with some side effects, including pneumonitis (lung inflammation) in 1%-5% of patients and a rare risk of type 1 diabetes (0.2% of cases). These side effects are related to its role as an immune checkpoint inhibitor, which can sometimes cause the immune system to attack healthy tissues.
46789What makes the drug combination of Sonidegib and Pembrolizumab unique for treating advanced cancers?
The combination of Sonidegib and Pembrolizumab is unique because it combines a PD-1 inhibitor, which helps the immune system attack cancer cells, with Sonidegib, a drug that targets a different pathway involved in cancer growth, potentially offering a novel approach for treating advanced cancers.
1341011Eligibility Criteria
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.Inclusion Criteria
My cancer has returned or spread and is confirmed by tests.
Women who can have children must have a negative pregnancy test within 7 days before joining the study.
I am fully active or restricted in physically strenuous activity but can do light work.
+37 more
Exclusion Criteria
I have an autoimmune disease needing regular immune system medications.
I had a severe reaction to previous immunotherapy that needed steroids or stopped treatment.
I have not had major surgery in the last 4 weeks.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Determine the maximum tolerated dose (MTD) of sonidegib in combination with pembrolizumab
21 days
3 visits (in-person)
Treatment
Participants receive sonidegib orally once daily on days 1-8 and pembrolizumab intravenously on day 8, repeating every 21 days for up to 24 cycles
Up to 72 weeks
24 cycles (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
1 visit (in-person)
Participant Groups
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.
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.
Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇪🇺 Approved in European Union as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇬🇧 Approved in United Kingdom as KEYTRUDA for:
- Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo ClinicRochester, MN
Mayo Clinic in FloridaJacksonville, FL
Mayo Clinic in RochesterRochester, MN
Mayo Clinic in ArizonaScottsdale, AZ
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. [2020]Pembrolizumab plus pemetrexed-platinum led to superior overall survival and progression-free survival, and a higher proportion of patients with a confirmed complete or partial response over placebo plus pemetrexed-platinum in the KEYNOTE-189 study. We aimed to evaluate prespecified exploratory patient-reported outcomes (PROs) in patients in KEYNOTE-189.
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study. [2021]The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab).
Pembrolizumab: first global approval. [2021]Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.
Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022]To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). [2022]Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.