Symptoms and General Pathology

All Conditions

Neoplasms

Death

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Cemiplimab

Immunoglobulins

Antineoplastic Agents, Immunological

Patients with metastatic CSCC: to distant sites or lymph nodes. Cemiplimab administered intravenously (IV) every 2 weeks (Q2W).

Patients with unresectable locally advanced CSCC. Cemiplimab administered IV Q2 weeks.

Patients with metastatic CSCC to distant sites or lymph nodes. Cemiplimab administered IV Q3 weeks.

Patients with advanced CSCC \[metastatic (nodal or distal) or unresectable locally advanced\] Cemplimab administered IV Q4 weeks.

Patients with advanced CSCC (metastatic \[nodal or distant\] or locally advanced) who received cemiplimab IV Q3W for at least 27 weeks without experiencing disease progression, will have the option to receive cemiplimab by subcutaneous (SC) injection Q3W (first 12 patients) or Q6W (next ≥ 6 patients) basis.

cemiplimab

Clinical Trial Management

Groups 1 to 4 To estimate the clinical benefit of cemiplimab monotherapy for patients with: metastatic (nodal or distant) cutaneous squamous cell carcinoma (CSCC), or unresectable locally advanced CSCC

Group 6 To provide additional efficacy and safety data for cemiplimab monotherapy in patients with advanced CSCC (metastatic \[nodal or distant\] or locally advanced treated with cemiplimab

Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Groups 1, 3, 4, and 6: Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 will be used to determine ORR. Group 2: Clinical response criteria will be used to determine ORR

Regeneron Pharmaceuticals

Nivolumab

Immune Checkpoint Inhibitors

Nivolumab 3mg/kg IV every 14 days until disease progression, unacceptable toxicity or up to 12 months.

Cutaneous squamous cell carcinoma (cSCC) is one of the most frequent malignancies worldwide, and an increasing incidence has been documented over the past decades. Despite optimal initial approach, which can be curative in the majority of cases, a proportion of patients present with locally advanced or unresectable disease, leading to significant morbidity. In addition, metastases of cSCC may affect 2 to 5% of individuals diagnosed with this disease. In the setting of advanced cSCC, no standard systemic treatment has been established, and treatment options are frequently adapted from those applied to squamous cell carcinoma arising from other sites, based on a low level of evidence and often with short-lived benefits.

cSCC are potentially immunogenic neoplasms with an unmet need for therapeutic options, having sun exposure and chronic inflammation as the most significant risk factors. Using the anti-PD1 monoclonal antibody nivolumab to treat patients with cSCC and planned scientific correlates, investigators believe that the safety and efficacy of immune activating therapy for this disease can be assessed.

This is a multi-center, Simon two-stage, phase II study to evaluate the safety and efficacy of the anti-PD1 monoclonal antibody nivolumab for systemic-treatment-naïve patients with metastatic and/or locally advanced cSCC.

The primary objective of the study is to evaluate the efficacy, as assessed by the best objective response rate (complete response + partial response) at 24 weeks according to RECIST criteria, of nivolumab in patients with advanced cSCC. Secondary objectives are to assess the safety/tolerability of the treatment, to determine the progression-free survival (PFS) and overall survival (OS) rates at 24 weeks, and to evaluate the objective response rate as assessed by immune-related response criteria (irRC). Treatment will be given every 14 days until disease progression, unacceptable toxicity or withdrawal of consent/patient decision. If the patient continues to benefit from treatment with nivolumab, treatment will be continued for up to 12 months. Patients will be reassessed at week 12 and every 12 weeks thereafter until week 52, and then as per discretion of the treating investigator. A tumor biopsy will be performed before treatment initiation, unless contraindicated and optional biopsies will be performed at week 13 and following disease progression. Serial blood samples will be obtained at baseline, during, and after treatment.

Nivolumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma

A Phase II of Study of Nivolumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma

To evaluate the efficacy, as assessed by the best objective response rate (complete response + partial response) at 24 weeks by RECIST 1.1, of nivolumab in patients with advanced cSCC.

To assess the safety and tolerability of nivolumab in patients with advanced cSCC.

To determine the progression free survival (PFS) rate at 24 weeks

To evaluate the efficacy, as assessed by the best objective response rate (complete response + partial response) at 24 weeks by immune-related response criteria (irRC), of nivolumab in patients with advanced cSCC.

Instituto do Cancer do Estado de São Paulo

Principal Investigator

Patients with advanced CSCC. IBI318 administered intravenously every 2 weeks.

IBI318 will be given fixed dose via intravenous (IV) infusion on Day 1 of each 14-day cycle until disease progression or loss of clinical benefit.

IBI318

The purpose of this study is to evaluate the safety and efficacy of IBI318 (anti-PD-1/PD-L1) in adult participants with metastatic (nodal or distant) cutaneous squamous cell carcinoma (CSCC), or unresectable locally advanced CSCC that is not amenable to surgery and/or radiation.

Study of IBI318 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

A Phase Ib/II, Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of IBI318 in Participants With Advanced Cutaneous Squamous Cell Carcinoma.

RECIST version 1.1 will be used to determine ORR by IRRC

RECIST version 1.1 will be used to determine ORR by investigator

RECIST version 1.1 will be used to determine DOR by investigator and IRRC

RECIST version 1.1 will be used to determine PFS by investigator and IRRC

To evaluate the safety and tolerability of IBI318 \[Adverse events (AEs), Serious Adverse Events (SAEs) \]

Innovent Biologics (Suzhou) Co. Ltd.

Infections

Skin and Connective Tissue Diseases

Virus Diseases

Skin Neoplasms

Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks

Cemiplimab administered intravenously as a single therapy every 3 weeks

Sumera Raoof, MD

Jeannie Hou, MD

To estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with locally advanced or metastatic CSCC, as assessed by overall response rate (ORR) and complete response rate (CRR) according to blinded independent review.

RP1 is a selectively replication competent herpes simplex virus type 1(HSV-1). This is a Phase 1/2, open-label, multicenter repeat-dosing study of RP1 alone and in combination with nivolumab in patients with advanced malignancies, and contains both single agent dose escalation, dose expansion to include nivolumab, and the combination in multiple Phase 2 cohorts in individual tumor types.

Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer

A Randomized, Controlled, Open-Label, Phase 2 Study of Cemiplimab as a Single Agent and in Combination With RP1 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Replimune Inc.

In a safety lead-in of 6 patients, subjects will receive 15mg of ruxolitinib twice daily (BID). After 4 weeks, if dose-limiting toxicities (DLT) are observed in 1 or fewer patients, the study will enter stage 1 of the Simon two-stage design where all subsequent patients will receive a starting dose of ruxolitinib 15mg BID.

Subjects will have regularly scheduled study visits at the clinical site on Day 1 and Day 15 (± 3 days) of the first 2 cycles, then on Day 1 (± 3 days) of every subsequent cycle (starting cycle 3), where safety assessments, including laboratory assessments, vital signs, and physical examinations will be performed.

Ruxolitinib will be administered orally twice daily during the entirety of each 28-day cycle.

Ruxolitinib

Alexander Wei, MD

In this open-label, multicenter, Phase II study, the investigators propose to evaluate the efficacy of ruxolitinib, an orally administered inhibitor of JAK1/2, in solid organ transplant recipients with advanced cSCC. In a safety lead-in of 6 patients, subjects will receive ruxolitinib 15mg twice daily (BID). After 4 weeks, if dose-limiting toxicities (DLT) are observed in 1 or fewer patients, the study will enter stage 1 of the Simon two-stage design where all subsequent patients will receive a starting dose of ruxolitinib 15mg BID. If more than 1 DLTs are observed, another cohort of 6 patients will be treated at a dose of 10mg BID. If less than 2 DLTs are observed at the new dose of 10mg, then the study will proceed to stage I using this dose; otherwise the study will stop.

Approximately 5.4 million individuals in the United States are diagnosed with non-melanoma skin cancers (NMSC) annually, with the incidence increasing over time. Twenty-five percent are cutaneous squamous cell carcinomas (cSCC), which affect up to 1,350,000 individuals and result in up to 12,000 deaths annually in the US alone. Immunosuppressed patients are particularly vulnerable to the development of highly aggressive or catastrophic cSCC. Patients receiving immunosuppressive therapy, such as solid organ transplant recipients (SOTRs), and HIV/AIDS patients have an estimated 60 to 250-fold increased risk of cSCC development. In renal SOTRs, cSCC represents over 70% of all malignancies that develop, with an incidence up to 200 times that of the general population. Post-transplant cSCC occurs at a younger age and is more aggressive than in non-transplant cohorts, with 30% of cSCC recurring within 1 year and up to 8% of disease associated with metastasis. The median survival from diagnosis of metastasis is 3 years.5 Cemiplimab, an anti-PD1 antibody, recently became the first agent to achieve regulatory approval for the treatment of advanced cSCC; however, due to the risk of graft rejection, the role of immunological checkpoint blockade in the SOTR population is extremely limited. Thus, although surgical excision is effective for sporadic cSCC, there remains a large unmet medical need for novel strategies for treatment and/or prevention of multiply recurrent, locally advanced, and metastatic cSCC, particularly in immunosuppressed patients.

Study of Ruxolitinib in Solid Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma

A Multi-Center Phase II Study of Ruxolitinib in Solid Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma

The primary endpoint is the overall response rate as defined as the best response, confirmed at ≥4 weeks, within the first 24 weeks of the start of study therapy, using RECIST v1.1 criteria.

Progression-free survival (PFS) (time alive without advanced cutaneous squamous cell carcinoma (cSCC) probabilities will be estimated

The length of time from the start of treatment that subjects with the disease are still alive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma	NCT02760498	Advanced Cutane...	cemiplimab	18 Years -	Regeneron Pharmaceuticals
Nivolumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma	NCT03834233	Advanced Cutane...	Nivolumab	18 Years -	Instituto do Cancer do Estado de São Paulo
Study of IBI318 in Patients With Advanced Cutaneous Squamous Cell Carcinoma	NCT04611321	Advanced Cutane...	IBI318	18 Years -	Innovent Biologics (Suzhou) Co. Ltd.
Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer	NCT04050436	Cutaneous Squam... Advanced Cutane... Metastatic Cuta...	Cemiplimab RP1	18 Years -	Replimune Inc.
Study of Ruxolitinib in Solid Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma	NCT04807777	Advanced Cutane...	Ruxolitinib	18 Years -	Columbia University
Nivolumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma	NCT03834233	Advanced Cutane...	Nivolumab	18 Years -	Instituto do Cancer do Estado de São Paulo
Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer	NCT04050436	Cutaneous Squam... Advanced Cutane... Metastatic Cuta...	Cemiplimab RP1	18 Years -	Replimune Inc.

Spots Global Cancer Trial Database for advanced cutaneous squamous cell carcinoma