Non-comparative Study of IFX-1 Alone or IFX-1+Pembrolizumab in Patients With Locally Advanced or Metastatic cSCC.
- Conditions
- SCC - Squamous Cell Carcinoma of Skin
- Interventions
- Registration Number
- NCT04812535
- Lead Sponsor
- InflaRx GmbH
- Brief Summary
This is an open-label, "non comparative", non-randomized, Phase II study. Patients will be enrolled in 2 treatment arms
- Detailed Description
This is an open-label, non-randomized, Phase II study. Patients will be enrolled in 2 treatment arms (Arm A: IFX-1 monotherapy; Arm B: IFX-1 + pembrolizumab combination therapy), both consisting of 2 stages whereas Arm B starts with a safety run in portion. Enrollment follows an optimal Simon's 2-stage design with an interim analysis of treatment response after Stage 1 prior to patient enrollment into Stage 2.
Arm B will start after ≥3 patients have been treated in Arm A and no toxicity concerns have emerged. In a safety run-in part of Arm B, escalating doses of IFX-1 will be investigated in combination with pembrolizumab in order to identify the MTD or RP2D. Patients will be treated until progression, occurrence of unacceptable toxicity, or treatment discontinuation for any other reason.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
- At least 18 years of age on day of signing informed consent
- Patients with biopsy-proven, histologically or cytologically confirmed (a.) locally advanced cSCC not amenable for curative treatment or (b.) metastatic cSCC. Patients must have been treated with all approved therapies for (a.) inoperable locally advanced cSCC contraindicated for radiation therapy or (b.) metastatic cSCC
- Eastern Cooperative Oncology Group performance status (ECOG PS) status of ≤1
- Patients must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.
- Patient provides written informed consent for the study.
- Patients with limited cSCC, who do not require systemic therapy
- Has a diagnosis of immunodeficiency or autoimmune disease, or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 3 weeks prior the first dose of study treatment
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab or IFX-1 and/or any of their excipients or had a severe (≥Grade 3) infusion-related reaction to treatments with other mAbs
- Patients who have undergone major surgery <4 weeks prior to starting study treatment
- Patients with known ≥Grade 3 (per National Cancer Institute common terminology criteria for adverse events [NCI CTCAE] v5.0 criteria) active systemic or cutaneous viral, bacterial, or fungal infection
- Has known active central nervous system metastases and/or carcinomatous meningitis.
- Patients with a history of other malignancies during the past 5 years
- Patients with congestive heart failure, Class III or IV, by New York Heart Association criteria
- Patients who are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study,
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: IFX-1 + pembrolizumab combination therapy IFX-1 + pembrolizumab combination therapy IFX-1 + pembrolizumab combination therapy Arm A: IFX-1 monotherapy IFX-1 IFX-1 monotherapy
- Primary Outcome Measures
Name Time Method ORR- Arm B Up to 36 months Investigator assessed best ORR for IFX-1 + pembrolizumab, with response being defined as best response of CR/confirmed CR (iCR) or PR/confirmed PR (iPR) per modified RECIST v1.1/iRECIST
TEAEs- Arm B Up to 36 months Frequency, severity, and investigational new drug (IND) attribution of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) according to Medical Dictionary for Regulatory Activities (MedDRA) coding (version valid at time of reporting) and the NCI CTCAE grading system (version 5.0, 27 November 2017)
ORR- Arm A Up to 36 months Investigator assessed best overall response rate (ORR) for IFX-1, with response being defined as best response of CR/confirmed CR (iCR) or PR/confirmed PR (iPR) per modified RECIST v1.1/iRECIST
DLT- Arm B Cycle 1 Day - Cycle 1 Day 36 Frequency of dose-limiting toxicities (DLTs) by dose cohort
- Secondary Outcome Measures
Name Time Method Disease control rate - Arm A Up to 36 months Disease control rate (CR/iCR+PR/iPR+SD)
Progression free survival- Arm B Up to 36 months Progression free survival-
Overall survival- Arm B Up to 36 months Overall survival
TEAEs- Arm A Up to 36 months Frequency, severity, and IND attribution of TEAEs and SAEs according to MedDRA coding (version valid at time of reporting) and the NCI CTCAE grading system v5.0
QoL - Arm B Up to 36 months Quality of Life
QoL- Arm A Up to 36 months Changes in QoL as per the European Organisation for Research and Treatment of Cancer (EORTC)-QoL questionnaire (QLQ)-C30 total score
Response (CR/iCR/PR/iPR) and SD- Arm B Up to 36 months Response (CR/iCR/PR/iPR) and SD duration
Progression-free survival (PFS)- Arm A Up to 36 months Progression free survival
Overall survival (OS)- Arm A Up to 36 months Overall survival (OS)
ADAs- Arm A Up to 27 months Development of human antidrug antibodies (ADAs) against IFX-1
Disease control rate- Arm B Up to 36 months Disease control rate (CR/iCR+PR/iPR+SD)
ADAs against IFX-1 - Arm B Up to 36 months Development of human ADAs against IFX-1
Trial Locations
- Locations (25)
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
St. Augustinus Hospital
🇧🇪Wilrijk, Belgium
CHU APHM la Timone / Aix Marseille University, Dermatology and Skin Cancer Department
🇫🇷Marseille, France
St. Louis Hospital
🇫🇷Paris, France
University Hospital Erlangen, Department of Dermatology
🇩🇪Erlangen, Germany
University Hospital Center of Poitiers, Department of Oncology
🇫🇷Poitiers, France
University Hospital Hamburg-Eppendorf
🇩🇪Hamburg, Germany
University Hospital Leipzig, Department of Dermatology, Venereology and Allergology
🇩🇪Leipzig, Germany
MD Anderson International Cancer Center Spain
🇪🇸Madrid, Spain
ICO Hospitalet
🇪🇸Barcelona, Spain
University Clinical Hospital of Salamanca
🇪🇸Salamanca, Spain
University Hospital Antwerp (UZA)
🇧🇪Edegem, Belgium
University Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Frankfurt University Clinic, Department of Dermatology, Venereology and Allergology
🇩🇪Frankfurt, Germany
University Hospital Tuebingen, Department of Dermatology
🇩🇪Tuebingen, Germany
Regional University Hospital of Malaga
🇪🇸Málaga, Spain
Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Orlando Health, Inc.
🇺🇸Orlando, Florida, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
University Hospital Center of Grenoble Alpes, Department of Dermatology
🇫🇷Grenoble, France
University Hospital Regensburg, Clinic and Policlinic for Dermatology
🇩🇪Regensburg, Germany
South Lyon Hospital Center
🇫🇷Lyon, France
University Duisburg-Essen, University Hospital Essen, Department of Dermatology
🇩🇪Essen, Germany