Pembrolizumab With or Without Vismodegib in Treating Metastatic or Unresectable Basal Cell Skin Cancer

Phase 1

Completed

Conditions: Skin Basal Cell Carcinoma

Interventions: Biological: Pembrolizumab
Drug: Vismodegib

Registration Number: NCT02690948

Lead Sponsor: Anne Chang

Brief Summary: This phase 1-2 trial studies how well pembrolizumab with or without vismodegib works in treating patients with skin basal cell cancer that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, are checkpoint inhibitors that stimulate immune response. Vismodegib may stop the growth of tumor cells by blocking signals needed for cell growth.

Detailed Description: This study is a non-randomized evaluation of pembrolizumab as a treatment for unresectable or metastatic basal cell carcinoma (BCC). Participants are assigned to treatment with pembrolizumab plus vismodegib or pembrolizumab monotherapy on the basis of suitability for treatment with smoothened (SMO) inhibitors such as vismodegib. Prospective participants who have progressed on vismodegib, are intolerant to or have a medical contra-indication to vismodegib may receive pembrolizumab monotherapy. Because treatment is non-randomized, no comparison between treatment groups is conducted.

PRIMARY OBJECTIVE To assess the overall response rate (ORR) of unresectable or metastatic BCC patients to pembrolizumab with or without vismodegib (all evaluable patients) at 18 weeks

SECONDARY OBJECTIVES

* To assess the ORR of unresectable or metastatic BCC patients to pembrolizumab monotherapy at 18 weeks

* To assess the ORR of unresectable or metastatic BCC patients to pembrolizumab monotherapy at 9 weeks

* To assess ORR of unresectable or metastatic BCC patients to pembrolizumab plus vismodegib at 18 weeks

* To assess ORR of unresectable or metastatic BCC patients to pembrolizumab plus vismodegib at 9 weeks

* To assess the safety and tolerability of pembrolizumab (either monotherapy or combination therapy) for unresectable or metastatic BCC.

* To assess the duration of response after pembrolizumab (either monotherapy or combination therapy)

* Incidence and severity of adverse events

* Correlative studies including programmed death-ligand 1 (PD-L1) expression pre-treatment, lymphocytic infiltrates pre- and post-treatment, mutational analysis pre- and post-treatment

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab Monotherapy	Pembrolizumab	Participants who previously received vismodegib and subsequently progressed will receive pembrolizumab IV over 30 minutes on day 1. Cycles are every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Pembrolizumab plus Vismodegib Combination Therapy	Pembrolizumab	Participants who have not progressed while receiving vismodegib will receive pembrolizumab IV over 30 minutes on day 1 and take vismodegib 150 mg by mouth daily. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Pembrolizumab plus Vismodegib Combination Therapy	Vismodegib	Participants who have not progressed while receiving vismodegib will receive pembrolizumab IV over 30 minutes on day 1 and take vismodegib 150 mg by mouth daily. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	18 weeks	The overall response rate (ORR) of participants with unresectable or metastatic basal cell carcinoma (BCC) after treatment with A) pembrolizumab monotherapy and B) pembrolizumab in combination with vismodegib, will be assessed as the percentage of participants with partial response (PR) or complete response (CR) as determined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria, after 9 and 18 weeks of treatment. ORR is calculated as the ratio of patients with CR or PR as a percentage of the participants evaluable for OR. RECIST criteria: * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Adverse Events	up to 2 years	Incidence of Adverse Events is assessed as the percentage of participants receiving treatment who experience adverse events of any grade, in participants receiving A) pembrolizumab monotherapy and B) pembrolizumab in combination with vismodegib. Enrolled participants receiving at least one dose of study agent and with at least one follow-up evaluation will be included.
Related Adverse Events	up to 2 years	Adverse events were assessed for relationship to pembrolizumab treatment. The outcome is reported as the number (without dispersion) of Grade 3 or higher adverse events considered possibly, probably, or definitely-related to pembrolizumab treatment,.
Duration of Response (DOR)	up to 2 years	The duration of response (DOR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria in participants receiving A) pembrolizumab monotherapy and B) pembrolizumab in combination with vismodegib, assessed as the median value for subjects who complete 9 and 18 weeks of treatment. RECIST criteria: * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria
Overall Survival (OS)	1 year	The overall survival (OS) participants with unresectable or metastatic basal cell carcinoma (BCC) after treatment with A) pembrolizumab monotherapy and B) pembrolizumab in combination with vismodegib, will be reported as the number and percentage of participants remaining alive 1 year after the start of treatment.
Progression-free Survival (PFS)	1 year	The progression-free survival (PFS) will be participants with unresectable or metastatic basal cell carcinoma (BCC) after treatment with A) pembrolizumab monotherapy and B) pembrolizumab in combination with vismodegib, will be reported as the percentage of participants without progression 1 year after the start of treatment.