Phase II Study of Pembrolizumab (MK-3475) as First Line Single Drug Therapy in Patients With Unresectable Squamous Cell Carcinoma of the Skin
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Carcinoma, Squamous Cell
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Response rate (RR)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to assess the efficacy and safety of pembrolizumab in patient with locally advanced or metastatic squamous cell carcinoma of the skin
Detailed Description
Agents blocking the Programmed Cell Death 1(PD1)/Programmed Cell Death 1-Ligand 1 (PD-L1) pathway have demonstrated objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression. PD-L1 expression by tumour cells is the strongest single predictor of response to anti-PD1 therapy (J Taube, R Anders et al, Clin Cancer Res 2014). Pembrolizumab (MK-3475) is a high-affinity humanized monoclonal anti-PD1 antibody. It leads to dual PD1-ligand blockade of PD-L1 and PD-L2 that may reactivate the immune surveillance and elicit anti-tumour response. It has antitumor activity in melanoma and NSCLC (phase III trials). Pembrolizumab might be of interest in unresectable squamous cell carcinomas of the skin (SCCS). Approximately 20% to 30% of non-melanoma skin cancers are SCCS. Most patients with primary SCCS have an excellent prognosis, but SCCS can progress to advanced stages that are impossible to treat by surgical excision or radiotherapy. Few therapeutic options are available for these tumors. Conventional chemotherapy, such as cisplatin-based combinations, has some efficacy, but the toxic effects of these combinations often prohibit their use in elderly patients. Epidermal Growth Factor (EGFR) signaling antagonists have activity only in a subset of patients. New therapeutic options are needed for patients with advanced SCCS. No trial evaluating pembrolizumab in human SCCS is ongoing. Investigators hypothesize that: i) PD-L1 is expressed in SCCS as in HNSCC ii) pembrolizumab may be effective as a single agent in patients with unresectable SCCS iii) Efficacy of pembrolizumab is correlated to PD-L1 expression in SCCS. Investigators therefore intend to determine the efficacy and safety of single agent pembrolizumab in all patients and in patients with PD-L1-positive unresectable SCCS naïve of chemotherapy and of EGFR inhibitors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Be willing and able to provide written informed consent/assent for the trial
- •Be more than 18 years of age on day of signing informed consent.
- •Be either affiliated to, or a beneficiary of, a social security category
- •Have metastatic disease, or locally advanced disease not amenable to surgery with documented progression
- •Be willing and able to undergo pre-treatment baseline biopsy of the tumor
- •PD-L1+ or PD-L1- tumors
- •Have measurable disease based on RECIST 1.1
- •Have a performance status of 0 or 1 on the Easter Cooperative Oncology Group (ECOG) Performance Scale.
- •Demonstrate adequate organ function as defined in Table 3, all screening labs should be performed within 10 days of treatment initiation.
- •Have recovered from major surgery or radiation therapy
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks or 5 half-lives (minimum 14 days), whichever is shorter, prior to the first dose of treatment.
- •Has received prior therapy with either chemotherapy or targeted therapy for the present tumor
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- •Has received radiation therapy within 4 weeks prior to study Day 1
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- •Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., Hepatitis C Virus RNA \[qualitative\] is detected).
- •Has known history of, or any evidence of active, non-infectious pneumonitis.
- •Has an active infection requiring systemic therapy
Arms & Interventions
Pembrolizumab 200 mg
Pembrolizumab 200 mg administered as intravenous (IV) infusion every 3 weeks up to 24 months or until progression or unacceptable toxicity develops.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Response rate (RR)
Time Frame: 15 weeks
Response rate (RR) at 15 weeks (RECIST v.1.1) in the whole sample by CT or MRI Response Evaluation Criteria in Solid Tumors with central radiology review
Secondary Outcomes
- RR in PD-L1-positive patients(15 weeks)
- Disease Control Rate using RECIST and modified RECIST v.1.1(15 weeks)
- Best RR using RECIST and modified RECIST v.1.1(24 months)
- Safety profile (NCI CTCAE v4.0)(up to 28 months)
- RR using modified RECIST 1.1(15 weeks)
- RR using RECIST and modified RECIST v.1.1(24 weeks)
- Overall Survival (OS)(up to 24 months)
- Progression Free Survival by RECIST 1.1 and modified RECIST 1.1(up to 24 months)
- Duration of response (DOR) by RECIST 1.1 and modified RECIST 1.1(up to 24 months)
- Duration of control by RECIST 1.1 and modified RECIST 1.1(up to 24 months)
- Time to disease progression by RECIST 1.1 and modified RECIST 1.1(up to 24 months)