Cutaneous Squamous Cell Carcinoma, Skin Cancer
Conditions
Keywords
Advanced Cutaneous Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Skin Cancer, Kidney Transplant Recipient, Chronic lymphocytic leukemia (CLL), Myeloma, Waldenstrom macroglobulinemia, Solid Organ Transplant Recipient, Immunosuppressed, Lymphoma
Brief summary
This is study is to evaluate the safety and efficacy of cosibelimab in special populations with advanced cutaneous squamous cell carcinoma (CSCC). The name of the drug involved in this research study is: -cosibelimab (a type of an anti-PD-L1 antibody)
Detailed description
This is a Phase IV, multi-site, multi-cohort, open-label clinical trial investigating the safety and efficacy of cosibelimab in special populations with advanced cutaneous squamous cell carcinoma (CSCC). Checkpoint Therapeutics is supporting this research study by providing the study drug, cosibelimab. Participants will be enrolled into one of two study groups: Group A or Group B. Cosibelimab is FDA-approved for the treatment of advanced cutaneous squamous cell carcinoma The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, Computerized Tomography (CT) scans, or Positron Emission (PET) scans, electrocardiograms (ECGs), Tumor biopsies and aspirations. It is expected that about 80 people will take part in this research study.
Interventions
DRUGCosibelimab
Anti-PD-L1 antibody, single dose vials, via intravenous (into the vein) infusion per protocol
DRUGPrednisone
Corticosteroid, per standard of care
DRUGSirolimus
mTOR Inhibitor, per standard of care
DRUGEverolimus
mTOR Inhibitor, per standard of care
Sponsors
Dana-Farber Cancer Institute
Checkpoint Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* COHORT A: Participant must have a history of kidney transplant (at least 6 months prior to enrollment). (A history of more than one kidney transplantation is permitted.) * COHORT B: Participant must have a diagnosis of a hematologic malignancy, including chronic myeloproliferative neoplasm (CMN) or an indolent non-Hodgkin's lymphoma (NHL), or multiple myeloma (MM). * Examples of indolent non-Hodgkin's lymphomas (NHL), including but not limited to: * Chronic lymphocytic leukemia (CLL) * Small cell lymphocytic lymphoma (SLL) * Follicular lymphoma (FL) * Lymphoplasmacytic lymphoma * Waldenström macroglobulinemia * Marginal zone lymphoma * Mantle cell lymphoma, indolent variety * Cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome) * Examples of chronic myeloproliferative neoplasms (CMN), including but not limited to: * Chronic myelogenous leukemia (CML) * Polycythemia vera (PV) * Primary myelofibrosis * Essential thrombocythemia (ET) * Chronic neutrophilic leukemia * Chronic eosinophilic leukemia * Examples of myeloma, including but not limited to: * Multiple myeloma (MM) * Smoldering myeloma * Participants must have histologically or cytologically confirmed diagnosis of cutaneous squamous cell carcinoma (CSCC). * Note: Mixed histology is acceptable (e.g. basosquamous, squamous cell carcinoma with adnexal differentiation), and other histologic variants (sarcomatoid carcinoma, spindle cell carcinoma, poorly differentiated carcinoma with squamous features). * Participant must have CSCC that is not amenable to surgery or radiation therapy, or recurrent despite prior surgery or radiation therapy, including locally advanced unresectable CSCC for which local therapy (surgery and/or radiation therapy) is not recommended. This includes CSCC occurring in patients who are not surgical candidates due to comorbidities and patients who refuse surgery (due to concerns about morbidity, disfigurement, etc). * Participants must have measurable disease as per PET Response Criteria in Solid Tumors version * (PERCIST 1.0),46 defined as any tumor (of any size) whose SUV lean (SUL) peak is greater than 1.5 times the mean SUL in the liver + 2 times its standard deviation. Mean SUL in the liver is measured in a 3-cm diameter spherical volume of interest (VOI), which is a measurement of the SUV background. * Age ≥18 years. Because no dosing or adverse event data are currently available on the use of cosibelimab in participants \<18 years of age, children are excluded from this study. * ECOG performance status 0-2 (see Appendix A for definitions of this and Karnofsky Performance Status). * Participants must meet the following organ and marrow function as defined below: * Absolute neutrophil count ≥1.0 K/mcL * Platelets ≥30 K/mcL * Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL * AST(SGOT) ≤ 2.5 × institutional ULN * ALT(SGPT) ≤ 2.5 × institutional ULN * Adequate renal function, defined as defined as estimated glomerular filtration rate (eGFR) ≥ 30 mL/min * Serum creatinine ≤ 3.0 x institutional ULN or ≤ 3.0 x baseline (grade ≤ 2 per CTCAE) * Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. * PD-1 and PD-L1 immune checkpoint antibodies are classified as pregnancy class D. For this reason, and because other therapeutic agents used in this trial are potentially teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 120 days after completion of cosibelimab administration. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 120 days after completion of cosibelimab administration. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Prior treatment within the past 12 months with any of the following classes of drugs: anti-PD-1 inhibitors, anti-PD-L1 inhibitors, or anti-CTLA-4 inhibitors. * Prior treatment within the past 6 months with CAR-T cell therapies, other cellular therapies, or multiagent cytotoxic chemotherapy regimens (e.g. R-CHOP). (Bispecific antibodies and EGFR- targeted therapies are permitted without a washout period.) * Participants who have adverse events due to prior anti-cancer therapy not recovered to Grade 1 or less, with the exception of alopecia, sensory neuropathy, and cytopenias. * Active autoimmune disease that is currently requiring systemic steroid treatment with prednisone \>10mg daily (or equivalent), anti-CD20 antibodies, intravenous immunoglobulin (IVIG) or JAK inhibitors (ruxolitinib, tofacitinib, upadacitinib, etc). * Severe interstitial lung disease (ILD), or a history of pneumonitis that has required oral or IV steroids in the past 5 years. * Participants who are receiving any other investigational agents for cancer within 2 weeks of study enrollment. * Participants who have uncontrolled, symptomatic infections, or infections requiring systemic antibiotics (prophylactic antimicrobials are permitted). * Participants who have uncontrolled or unstable brain metastases (or other CNS metastases) for whom systemic steroids are required. These patients are excluded because steroids may interfere with the effectiveness of immune checkpoint therapy. * Uncontrolled or significant cardiovascular disease. * Current need for dialysis (hemodialysis or peritoneal dialysis). * History of stem cell transplant or bone marrow transplant * Psychiatric illness or social situation that would preclude study compliance. * Pregnant and breastfeeding women are excluded from this study because cosibelimab is classified as pregnancy class D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cosibelimab, breastfeeding should be discontinued if the mother is treated with cosibelimab. * Participants with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the study drug are excluded. * COHORT A ONLY: * History of organ transplant other than kidney, including a heart, lung, or liver transplant, etc, with the exception of cornea transplantation. Cornea transplant is allowed if participant is not taking systemic immunosuppressive medication expressly for the purpose of corneal allograft. * History of severe allergic reaction attributed to sirolimus or everolimus, or other absolute contraindication to mTOR inhibitor, as determined by the treating physician. * COHORT B ONLY: History of any solid organ transplant, with the exception of cornea transplantation. Cornea transplant is allowed if participant is not taking systemic immunosuppressive medication expressly for the purpose of corneal allograft.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (BORR) | Up to 102 weeks. | BORR is defined as the proportion of participants whose best overall responses are complete metabolic response (CMR) and partial metabolic response (PMR). Per PERCIST 1.0 for target lesions, CMR is visual disappearance of all metabolically active tumor, and PMR is at least a 30% decrease in SUL peak (minimum 0.8-unit decrease) in the lesion with greatest uptake, not necessarily the same lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events (TEAEs) Rate | Treatment duration is up to 51 weeks, and adverse events will be collected through 30 days following the end of treatment. | TEAEs rate is defined as the proportion of participants who experience one or more adverse events that emerge or worsen after the initiation of study treatment. |
| Immune-related Adverse Events (AE) Rate | Treatment duration is up to 51 weeks, and adverse events will be collected through 30 days following the end of treatment. | The immune-related AE rate is defined as the proportion of participants who experience at least one adverse event considered by the investigator to be immune-related during the study treatment period. |
| Allograft Rejection and Allograft Loss Rate in Cohort A | Up to 51 weeks. | Allograft rejection loss rate is defined as the proportion of participants in Cohort A who experience allograft rejection or allograft loss, as determined by elevated serum creatinine, urine protein levels, donor-derived cell-free DNA (dd-cfDNA), renal biopsy findings, or the need for renal replacement therapy. |
| Median Progression-Free Survival (PFS) | Tumor assessments will be performed before Cycle 3, 5 Day 1 (28-day cycles) and every 4 cycles through Cycle 17. Follow-up assessments will occur on Cycle 18, 21, 29, and 33 Day 1. | PFS is defined as the time from registration to the earlier of progressive metabolic disease (PMD), as defined by PERCIST 1.1, or death from any cause. PFS will be estimated using the Kaplan-Meier method. Participants who are alive without documented disease progression at the time of analysis will be censored at the date of their last disease evaluation. |
| Duration of Response (DOR) | 2 years | DOR, defined according to PERCIST 1.1, is measured using the Kaplan-Meier method from the first documentation of complete metabolic response (CMR) or partial metabolic response (PMR), whichever occurs first, to the earliest date of objectively documented recurrent or progressive metabolic disease (PMD), using the lowest recorded measurements since treatment initiation as the reference, or death from any cause. Participants without documented events will be censored at the date of their last disease evaluation. |
| Median Overall Survival (OS) | Up to 147 weeks | OS based on Kaplan-Meier method is defined as time from date of first dose until the date of death due to any cause. Participants are censored as date last known alive. |
| Median Disease Specific Survival (DSS) | Up to 102 weeks. | DSS based on Kaplan-Meier method is defined as the time from study enrollment to death specifically due to advanced cutaneous squamous cell carcinoma (CSCC). Deaths from other causes are censored at the time of occurrence. |
| Median Circulating Tumor DNA (ctDNA) Levels | Up to 102 weeks. | ctDNA will be assessed from plasma using a personalized mPCR-NGS-based assay (Signatera™). ctDNA levels will be quantified as mean tumor molecules per milliliter of plasma (MTM/mL). |
Countries
United States
Contacts
CONTACTAnn Silk, MD
PRINCIPAL_INVESTIGATORAnn Silk, MD
Dana-Farber Cancer Institute
Outcome results
None listed