Symptoms and General Pathology

All Conditions

Neoplasms

Musculoskeletal Diseases

Mouth and Tooth Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Syndrome

Basal Cell Nevus Syndrome

Nevus, Pigmented

Nevus

Melanoma

Nevi and Melanomas

Neoplasms by Histologic Type

Cysts

Odontogenic Cysts

Jaw Cysts

Bone Cysts

Carcinoma

Carcinoma, Basal Cell

Neoplasms, Glandular and Epithelial

Neoplasms, Basal Cell

Neoplastic Syndromes, Hereditary

Bone Diseases

Bone Diseases, Developmental

Jaw Diseases

Stomatognathic Diseases

Congenital Abnormalities

Abnormalities, Multiple

Genetic Diseases, Inborn

Nevoid Basal Cell Carcinoma Syndrome

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients will receive a two week run-in of Vismodegib 150 mg PO daily followed by concurrent Nivolumab 480 mg IV every 4 weeks and Vismodegib 150 mg PO daily.

In an exploratory fashion, patients will have the option to receive combination Ipilimumab 1 mg/kg IV every 6 weeks and Nivolumab 360 mg IV every 3 weeks at the time of disease progression.

Vismodegib

Richard Carvajal, MD.

This is a single-arm, phase II study to assess the efficacy of combined SMO and PD-1 inhibition with Vismodegib (SMO inhibitor) and Nivolumab (anti-PD-1 antibody) in BCNS patients (target enrollment of 22 patients), with a primary endpoint of 18-month disease control rate. The purpose of this study is to test the hypothesis that Nivolumab and Vismodegib will improve the percentage of BCNS patients who achieve disease control (defined as total tumor burden \<50% of baseline) at 18 months from 50% to 80%. Baseline and on-treatment biopsies will be obtained to characterize the immune effects of combined SMO and PD-1 inhibition.

Basal cell carcinoma (BCC) is by far the most common form of human malignancy, affecting more than 3.5 million Americans each year. Aberrant activation of the Hedgehog (Hh) pathway, typically through loss of the receptor Patched (PTCH) or oncogenic activation of Smoothened (SMO), has been identified as the primary driver of BCC growth and development. In particular, up to 1 in 57,000 individuals in the US are affected by a rare, autosomal dominant disorder characterized by mutations in protein patched homolog 1 (PTCH1) known as basal cell nevus syndrome (BCNS). These patients can develop dozens to hundreds of BCCs at any one time (1-5). Surgical removal of the entire tumor burden is not feasible.

Hh-targeted therapies employing inhibitors of SMO (i.e., Vismodegib, Sonidegib) have shown remarkable efficacy in reducing tumor burden in BCC patients. However, the sustained clinical utility of these agents has been hampered by the rapid development of clinical resistance, significant tumor recurrence, and toxicity. Treatment strategies directed at finding additional molecular or immunological targets may enhance the possibility of sustained remission and/or cure of these tumors. Emerging data from our research group and others suggest the therapeutic efficacy of SMO inhibition may be dependent on immunological mechanisms. Hh inhibition appears to increase T cell recruitment and activation as well as upregulate major histocompatibility complex (MHC) class I expression on tumor cells. These data, together with case reports demonstrating the efficacy of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death-1 (PD-1) inhibition in Hh inhibitor-naïve and resistant BCCs, support a role for anti-tumor immunity in BCC and underscore the potential enhanced therapeutic efficacy of combined SMO and immunological checkpoint inhibition.

Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome

Trial of Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome (BCNS)

Defined as the percentage of patients achieving a total tumor burden \<50% of baseline tumor burden

Testing safety and toxicity assessed using CTCAE v5.0 criteria

DCR is defined as the percentage of subjects who have achieved complete response (CR), partial response (PR), or stable disease (SD) based on assessments per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

For subjects who demonstrate CR or PR, based on assessments per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.

Columbia University

Assistant Professor of Medicine at the Columbia University Medical

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome	NCT03767439	Basal Cell Nevu...	Vismodegib Nivolumab Ipilimumab	18 Years -	Columbia University
Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome	NCT03767439	Basal Cell Nevu...	Vismodegib Nivolumab Ipilimumab	18 Years -	Columbia University

Spots Global Cancer Trial Database for basal cell nevus syndrome (bcns)