Non-comparative Study of IFX-1 Alone or IFX-1+Pembrolizumab in Patients With Locally Advanced or Metastatic cSCC.

Study Overview
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Brief Summary
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This is an open-label, non comparative, non-randomized, Phase II study. Patients will be enrolled in 2 treatment arms

Detailed Description
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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.

Official Title
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Open Label, Multicenter Phase II Study of the C5a Antibody IFX-1 Alone or IFX-1 + Pembrolizumab in Patients With PD-1 or PD-L1 Resistant/Refractory Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma (cSCC)

Conditions
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SSC

Intervention / Treatment
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* Drug: IFX-1
* Drug: IFX-1 + pembrolizumab combination therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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,

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Arm A: IFX-1 monotherapy; Arm B: IFX-1 + in combination with approved dosing scheme of pembrolizumab
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: IFX-1 monotherapy<br>IFX-1 monotherapy | Drug: IFX-1<br>* IFX-1 Monotherapy<br>|
| Experimental: Arm B: IFX-1 + pembrolizumab combination therapy<br>IFX-1 + pembrolizumab combination therapy | Drug: IFX-1 + pembrolizumab combination therapy<br>* IFX-1 + pembrolizumab combination therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR- Arm A | 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 | Up to 36 months | 
| DLT- Arm B | Frequency of dose-limiting toxicities (DLTs) by dose cohort | Cycle 1 Day - Cycle 1 Day 36 | 
| ORR- Arm B | 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 | Up to 36 months | 
| TEAEs- Arm B | 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) | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate - Arm A | Disease control rate (CR/iCR+PR/iPR+SD) | Up to 36 months | 
| Progression-free survival (PFS)- Arm A | Progression free survival | Up to 36 months | 
| Overall survival (OS)- Arm A | Overall survival (OS) | Up to 36 months | 
| TEAEs- Arm A | 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 | Up to 36 months | 
| ADAs- Arm A | Development of human antidrug antibodies (ADAs) against IFX-1 | Up to 27 months | 
| QoL- Arm A | Changes in QoL as per the European Organisation for Research and Treatment of Cancer (EORTC)-QoL questionnaire (QLQ)-C30 total score | Up to 36 months | 
| Response (CR/iCR/PR/iPR) and SD- Arm B | Response (CR/iCR/PR/iPR) and SD duration | Up to 36 months | 
| Disease control rate- Arm B | Disease control rate (CR/iCR+PR/iPR+SD) | Up to 36 months | 
| Progression free survival- Arm B | Progression free survival- | Up to 36 months | 
| Overall survival- Arm B | Overall survival | Up to 36 months | 
| QoL - Arm B | Quality of Life | Up to 36 months | 
| ADAs against IFX-1 - Arm B | Development of human ADAs against IFX-1 | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCC, metastatic, locally advanced