PD-1 in Patients With Advanced Basal Cell Carcinoma Who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or Were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy

• ClinicalTrials.gov Identifier: NCT03132636
• Recruitment Status: Active, not recruiting
• First Posted: April 28, 2017
• Last Update Posted: March 23, 2022
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: April 24, 2017
• First Posted Date: April 28, 2017
• Last Update Posted Date: March 23, 2022
• Actual Study Start Date: June 29, 2017
• Actual Primary Completion Date: May 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2019)

• Objective Response Rate (ORR) for metastatic Basal Cell Carcinoma (BCC) [ Time Frame: Baseline to 93 weeks ]
  ORR for metastatic BCC measured by RECIST version 1.1
• ORR for unresectable locally advanced BCC [ Time Frame: Baseline to 93 weeks ]
  ORR for unresectable locally advanced BCC measured by Composite Response Criteria

Original Primary Outcome Measures (submitted: April 24, 2017)

• Overall Response Rate (ORR) for metastatic Basal Cell Carcinoma (BCC) [ Time Frame: Baseline to 93 weeks ]
  ORR for metastatic BCC measured by RECIST version 1.1
• ORR for unresectable locally advanced BCC [ Time Frame: Baseline to 93 weeks ]
  ORR for unresectable locally advanced BCC measured by Composite Response Criteria

Current Secondary Outcome Measures (submitted: December 10, 2019)

• Duration of Response (DOR) [ Time Frame: Time from the first observed confirmed response to disease progression or death, up to approximately 121 weeks ]
  DOR assessed by time from the first observed confirmed response (CR or PR) to disease progression or death, up to approximately 121 weeks (from first response assessment until end of post-treatment follow up)
• Complete Response (CR) Rate [ Time Frame: From date of treatment until best objective response of CR after starting cemiplimab, up to approximately 121 weeks ]
  CR rate (per central review) assessed from date of treatment until best objective response of CR after starting cemiplimab treatment, up to approximately 121 weeks (from first response assessment until end of post-treatment follow up).
• Progression Free Survival (PFS) [ Time Frame: From date of treatment until date of death up to approximately 121 weeks ]
  PFS assessed from date of treatment until date of death, up to approximately 121 weeks
• Overall Survival (OS) [ Time Frame: From date of treatment until date of death, up to approximately 121 weeks ]
  OS assessed from date of treatment until date of death, up to approximately 121 weeks
• Change in scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: From date of treatment until date of first documented progression or date of death, up to approximately 93 weeks ]
  Change in scores of patient-reported outcomes in EORTC QLQ-C30 assessed from date of treatment until date of first documented progression or date of death, up to approximately 93 weeks
• Change in scores of patient-reported outcomes in Skindex-16 [ Time Frame: From date of treatment until date of first documented progression or date of death, up to approximately 93 weeks ]
  From date of treatment until date of first documented progression or date of death, assessed up to approximately 93 weeks
• Incidence of treatment emergent adverse events (TEAEs) [ Time Frame: Up to week 121 ]
• Concentration at end of infusion (Ceoi) [ Time Frame: Up to week 121 ]
• Pre-infusion concentration (Ctrough) [ Time Frame: Up to week 121 ]
• Time of end of infusion (teoi) [ Time Frame: Up to week 121 ]
• Anti-cemiplimab antibodies [ Time Frame: Up to week 121 ]

Original Secondary Outcome Measures (submitted: April 24, 2017)

• Duration of Response (DOR) [ Time Frame: Time from the first observed confirmed response to disease progression or death, up to approximately 119 weeks ]
  DOR assessed by time from the first observed confirmed response (CR or PR) to disease progression or death, up to approximately 119 weeks (from first response assessment until end of post-treatment follow up)
• Complete Response (CR) Rate [ Time Frame: From date of treatment until best overall response of CR after starting REGN2810, up to approximately 119 weeks ]
  CR rate (per central review) assessed from date of treatment until best overall response of CR after starting REGN2810 treatment, up to approximately 119 weeks (from first response assessment until end of post-treatment follow up).
• Progression Free Survival (PFS) [ Time Frame: From date of treatment until date of death up to approximately 119 weeks ]
  PFS assessed from date of treatment until date of death, up to approximately 119 weeks
• Overall Survival (OS) [ Time Frame: From date of treatment until date of death, up to approximately 119 weeks ]
  OS assessed from date of treatment until date of death, up to approximately 119 weeks
• Change in scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: From date of treatment until date of first documented progression or date of death, up to approximately 93 weeks ]
  Change in scores of patient-reported outcomes in EORTC QLQ-C30 assessed from date of treatment until date of first documented progression or date of death, up to approximately 93 weeks
• Change in scores of patient-reported outcomes in Skindex-16 [ Time Frame: From date of treatment until date of first documented progression or date of death, up to approximately 93 weeks ]
  From date of treatment until date of first documented progression or date of death, assessed up to approximately 93 weeks

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PD-1 in Patients With Advanced Basal Cell Carcinoma Who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or Were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy
• Official Title: A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1, in Patients With Advanced Basal Cell Carcinoma Who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or Were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy
• Brief Summary: The primary objective is to estimate the objective response rate (ORR) for metastatic Basal Cell Carcinoma (BCC) (group 1) and for unresectable locally advanced BCC (group 2) when treated with cemiplimab as a monotherapy
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Basal Cell

Intervention

Drug: cemiplimab

Regimen as per protocol

Other Names:

• REGN2810
• Libtayo

Study Arms

• Experimental: Group 1- metastatic BCC
  Administration of cemiplimab in accordance with protocol dosing regimen
  Intervention: Drug: cemiplimab
• Experimental: Group 2 - unresectable locally advanced BCC
  Administration of cemiplimab in accordance with protocol dosing regimen
  Intervention: Drug: cemiplimab

Publications *

• Stratigos AJ, Sekulic A, Peris K, Bechter O, Prey S, Kaatz M, Lewis KD, Basset-Seguin N, Chang ALS, Dalle S, Orland AF, Licitra L, Robert C, Ulrich C, Hauschild A, Migden MR, Dummer R, Li S, Yoo SY, Mohan K, Coates E, Jankovic V, Fiaschi N, Okoye E, Bassukas ID, Loquai C, De Giorgi V, Eroglu Z, Gutzmer R, Ulrich J, Puig S, Seebach F, Thurston G, Weinreich DM, Yancopoulos GD, Lowy I, Bowler T, Fury MG. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):848-857. doi: 10.1016/S1470-2045(21)00126-1. Epub 2021 May 14.
• Li R, Lee G, Huang M, El-Sherief A. Rare basal cell metastasis of a basal-squamous skin collision tumour to the lung and axillary lymph node. BMJ Case Rep. 2019 Oct 3;12(10). pii: e231487. doi: 10.1136/bcr-2019-231487.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 24, 2017): 137
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 29, 2023
• Actual Primary Completion Date: May 20, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Confirmed diagnosis of invasive BCC
• Progression of disease on hedgehog inhibitor (HHI) therapy or intolerance of prior HHI therapy
• At least 1 measurable lesion
• ≥18 years of age
• Hepatic function, renal function, bone marrow function in defined lab-value-ranges
• Anticipated life expectancy >12 weeks
• Consent to provide archived tumor biopsy material (all patients)
• Group 2: consent to undergo research biopsies
• Group 2: must not be a candidate for radiation therapy or surgery
• Comply with study procedures and site visits
• Sign Subject Information Sheet and Informed Consent Form

Key Exclusion Criteria:

• Ongoing or recent significant autoimmune disease
• Prior treatment with specific pathway-blockers (PD-1/PD-L1)
• Prior treatment with immune-modulating agents within 28 days before cemiplimab
• Untreated brain metastasis that may be considered active
• Immunosuppressive corticosteroid doses (>10mg prednisone) within 28 days prior to treatment with cemiplimab
• Active infections requiring therapy, including HIV, hepatitis
• Pneumonitis within the last 5 years
• Cancer treatment other than radiation therapy, including investigational or standard of care, within 30 days prior to treatment with cemiplimab
• Documented allergic reactions or similar to antibody treatments
• Concurrent malignancies other than BCC, other than those with negligible risk of metastases or death
• Any acute or chronic psychiatric problems
• Having received a solid organ transplantation
• Inability to undergo contrast radiological assessments
• Breastfeeding, pregnant, women of childbearing potential not using contraception

Note: Other protocol-defined inclusion/exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, France, Germany, Greece, Italy, Spain, Switzerland, United States

Administrative Information

• NCT Number: NCT03132636
• Other Study ID Numbers: R2810-ONC-1620; 2016-003122-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: March 2022