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

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)

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

Study Overview

• Status: Terminated
• Conditions: SCC - Squamous Cell Carcinoma of Skin
• Intervention / Treatment: Drug: Vilobelimab; Drug: Vilobelimab + pembrolizumab combination therapy

Detailed Description

This is an open-label, non-randomized, Phase II study. Patients will be enrolled in 2 treatment arms (Arm A: Vilobelimab monotherapy; Arm B: Vilobelimab + 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 Vilobelimab will be investigated in combination with pembrolizumab in order to identify the maximum tolerated dose (MTD) or recommended Phase II dose (RP2D). Patients will be treated until progression, occurrence of unacceptable toxicity, or treatment discontinuation for any other reason.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • University Hospital Antwerp (UZA)
  • Wilrijk, Belgium, 2610
    • St. Augustinus Hospital
• France
  • Grenoble, France, 38700
    • University Hospital Center of Grenoble Alpes, Department of Dermatology
  • Lyon, France, 69495
    • South Lyon Hospital Center
  • Marseille, France, 13385
    • CHU APHM la Timone / Aix Marseille University, Dermatology and Skin Cancer Department
  • Paris, France, 75010
    • St. Louis Hospital
  • Poitiers, France, 86021
    • University Hospital Center of Poitiers, Department of Oncology
• Germany
  • Erlangen, Germany, 91054
    • University Hospital Erlangen, Department of Dermatology
  • Essen, Germany, 45147
    • University Duisburg-Essen, University Hospital Essen, Department of Dermatology
  • Frankfurt, Germany, 60590
    • Frankfurt University Clinic, Department of Dermatology, Venereology and Allergology
  • Hamburg, Germany, 20246
    • University Hospital Hamburg-Eppendorf
  • Leipzig, Germany, 04103
    • University Hospital Leipzig, Department of Dermatology, Venereology and Allergology
  • Regensburg, Germany, 93053
    • University Hospital Regensburg, Clinic and Policlinic for Dermatology
  • Tuebingen, Germany, 72076
    • University Hospital Tuebingen, Department of Dermatology
• Spain
  • Barcelona, Spain, 08035
    • University Hospital Vall d'Hebron
  • Barcelona, Spain, 08908
    • ICO Hospitalet
  • Madrid, Spain, 28033
    • MD Anderson International Cancer Center Spain
  • Málaga, Spain, 29010
    • Regional University Hospital of Malaga
  • Salamanca, Spain, 37007
    • University Clinical Hospital of Salamanca
• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Anschutz Cancer Pavilion
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc.
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. All patients to be included must have progressed on PD-1- or PD-L1-inhibitory antibody therapy.

• 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. PD-1 treatment progression is defined by meeting all of the following criteria:

  1. Has received ≥2 doses of an anti-PD-1/L1 mAb that has been approved for treatment of cSCC or any solid tumor
  2. Has demonstrated PD/iCPD after PD-1/L1 inhibitor treatment as defined by RECIST v1.1/iRECIST. The initial evidence of disease progression is to be confirmed by a second assessment ≥4 weeks from the date of the first documented disease progression, unless there is rapid clinical progression.
  3. Disease progression has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• The PD-1-/PD-L1 infusion must have been the most recent treatment for locally advanced or metastatic cSCC.

• In addition to providing the material for ensuring the diagnosis as stated in inclusion criterion 2a for patients with locally advanced cSCC, patients must consent to undergo the following biopsies (at each time point a punch biopsy of externally visible cSCC lesions or a biopsy of material from accessible metastases) for biomarker assessments:

  1. At baseline prior to the first administration of the investigational therapy and if possible, within 7 days prior to initiation of study treatment administration (mandatory for all patients)
  2. For Stage 2 patients only: on Cycle 2 Day 1 (±3 days) (mandatory)
  3. For Stage 2 patients only: at the time of CR/iCR/PR/iPR (optional, to be conducted only if the investigator considers this biopsy as clinically possible and potentially informative)
  4. For Stage 2 patients only: At the time of tumor progression (optional, to be conducted only if the investigator considers this biopsy as clinically possible and potentially informative).

• Patients must have the following minimum washout before first study treatment administration from previous treatments:

  1. ≥4 weeks for mAbs, systemic cytotoxic anticancer therapy, treatment with other anticancer investigational agents
  2. ≥3 weeks for local radiation therapy
• Eastern Cooperative Oncology Group performance status (ECOG PS) status of ≤1
• Adequate organ function
• Patient (or legally acceptable representative if applicable) provides written informed consent for the study.

Exclusion Criteria:

• Patients with limited cSCC, who do not require systemic therapy
• Has known active central nervous system metastases and/or carcinomatous meningitis.

Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for ≥4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for ≥14 days prior to first dose of study treatment.

• 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
• Patients who have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen 4, OX 40, CD137) and was discontinued from that treatment due to a ≥Grade 3 irAE
• 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 fulfil inclusion criterion 6 (washout times) but who have not recovered from side effects of such therapies
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Patients who have undergone major surgery <4 weeks prior to starting study treatment
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of 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
• Patients with known history of Hepatitis B or C infections or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
• Patients who have a history of human immunodeficiency virus infection
• Patients who have a history of interstitial lung disease
• Patients who have had an allogeneic tissue/solid organ transplant
• Patients with a history of other malignancies during the past 5 years.
• Patients who are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 3 months after the last dose of IFX-1 or 120 days after the last dose of pembrolizumab
• Women of childbearing potential (WOCBP) who have a positive serum pregnancy test result within 7 days before treatment
• Male patients and WOCBP who do not agree to practice an effective method of contraception during study and until 3 months after last dose of IFX-1 or 120 days after last dose of pembrolizumab
• Patients with congestive heart failure, Class III or IV, by New York Heart Association criteria
• Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment
• Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Vilobelimab monotherapy; Vilobelimab monotherapy was administered as a 30-minute (-5 / +10 minutes) intravenous infusion as follows: 800 mg on Days 1, 4, 8, and 15, followed by 1600 mg Q2W starting on Day 22 of Cycle 1 until end of treatment (EOT)	Drug: Vilobelimab; Vilobelimab Monotherapy
Experimental: Arm B: Regimen 1: Vilobelimab + pembrolizumab combination therapy; Vilobelimab was administered as a 30-minute (-5/+10 minutes) intravenous infusion as follows: 400 mg on Days 1, 4, 8, and 15, followed by 800 mg Q2W starting on Day 22 of Cycle 1 until EOT. Vilobelimab treatment was combined with pembrolizumab, administered as a 30-minute (-5/+10 minutes) intravenous infusion at a dose of 400 mg starting at Day 8 of Cycle 1 and then Q6W on Day 1 of each treatment cycle	Drug: Vilobelimab + pembrolizumab combination therapy; Vilobelimab + pembrolizumab combination therapy; Other Names: KEYTRUDA®
Experimental: Arm B: Regimen 2: Vilobelimab + pembrolizumab combination therapy; Vilobelimab was administered as a 30-minute (-5/+10 minutes) intravenous infusion as follows: 600 mg on Days 1, 4, 8, and 15, followed by 1200 mg Q2W starting on Day 22 of Cycle 1 until EOT. Vilobelimab treatment was combined with pembrolizumab, administered as a 30-minute (-5/+10 minutes) intravenous infusion at a dose of 400 mg starting at Day 8 of Cycle 1 and then Q6W on Day 1 of each treatment cycle	Drug: Vilobelimab + pembrolizumab combination therapy; Vilobelimab + pembrolizumab combination therapy; Other Names: KEYTRUDA®
Experimental: Arm B: Regimen 3: Vilobelimab + pembrolizumab combination therapy; Vilobelimab was administered as a 30-minute (-5/+10 minutes) intravenous infusion as follows: 800 mg on Days 1, 4, 8, and 15, followed by 1600 mg Q2W starting on Day 22 of Cycle 1 until EOT. Vilobelimab treatment was combined with pembrolizumab, administered as a 30-minute (-5/+10 minutes) intravenous infusion at a dose of 400 mg starting at Day 8 of Cycle 1 and then Q6W on Day 1 of each treatment cycle	Drug: Vilobelimab + pembrolizumab combination therapy; Vilobelimab + pembrolizumab combination therapy; Other Names: KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response Rate (Best ORR) - Arm A and Arm B	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and immunologic RECIST (iRECIST) for target lesions and assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥30% decrease in the sum of the diameters of target lesions; Best Overall Response (OR) = CR + PR, from the start of the treatment until PD/recurrence.	Up to 36 months
Dose-limiting Toxicity (DLT) - Arm B	Frequency of dose-limiting toxicities (DLTs) by dose cohort.	Cycle 1 Day 1 - Cycle 1 Day 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate - Arm A and Arm B	Disease control rate is defined as the relative number of patients achieving stable disease (SD/iSD), CR/iCR or PR/iPR according to modified RECIST v1.1 (including clinical response)/iRECIST response.	Up to 36 months
Progression-free Survival (PFS)- Arm A and Arm B	PFS is defined as the time from first study treatment administration to progression (i.e. PD, iUPD, iCPD) or death. Patients without progression are censored at their last visit/study treatment administration.	Up to 36 months
Overall Survival (OS)- Arm A and Arm B	Overall survival is defined as the time from first study treatment administration to death. Patients alive when they discontinue the study are censored at their last recorded date of being alive.	Up to 36 months
Antidrug Antibodies (ADAs) - Arm A and Arm B	Development of human antidrug antibodies (ADAs) against Vilobelimab. In contrast to the time frame of the secondary efficacy outcome measures (3.-5., 7.-8), which were reported until EOS (up to 36 months), the time frames of ADAs (6.) and PK (9.) are measured (only) until first FU. Therefore, the time frame is different, i.e. 24 months of treatment until EOT + (approx.) 12 weeks/3 months until first FU up to 27 months.	Up to 27 months
Quality of Life (QoL) - Arm A and Arm B	The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 version 3.0 measures the different aspects that define the quality of life of cancer patients or survivors. The reported total score ranges from 0 to 100 whereas a higher score represents a higher response level. The total score was calculated as mean of all 15 single scores. It was only calculated if all 15 single scores were non-missing (for more information see Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 Scoring Manual (3rd Edition). Published by: European Organisation for Research and Treatment of Cancer, Brussels 2001.). The absolute changes from baseline are presented.	Up to 36 months
Response (Complete Response (CR) / CR According to iRECIST (iCR) / Partial Response (PR) / PR According to iRECIST (iPR)) and Stable Disease (SD) Duration - Arm A and Arm B	Duration of stable disease is defined as the time from first diagnosis of response or stable disease (i.e., CR/iCR/PR/iPR/SD/iSD) to progression (i.e. progressive disease (PD), unconfirmed progressive disease according to iRECIST (iUPD), confirmed progressive disease (iCPD)) or death. Responding and stable patients without progression are censored at their last visit/study treatment administration. Patients who never respond or have a stable disease are excluded from this analysis.	Up to 36 months
Plasma Concentration of Vilobelimab - Arm A and Arm B	The plasma concentration of vilobelimab was assessed at different time points pre- and post-dose. The post-dose Cycle 1 Day 22 values correspond to Cmax and the pre-dose Cycle 1 Day 8, pre-dose Cycle 1 Day 22, pre-dose Cycle 2 Day 1 and per-dose Cycle 5 Day 1 values to Ctrough. In contrast to the time frame of the secondary efficacy outcome measures (3.-5., 7.-8), which were reported until EOS (up to 36 months), the time frames of ADAs (6.) and PK (9.) are measured (only) until first FU. Therefore, the time frame is different, i.e. 24 months of treatment until EOT + (approx.) 12 weeks/3 months until first FU up to 27 months.	Up to 27 months

Collaborators and Investigators

• Sponsor: InflaRx GmbH
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Prof. Dr. D. Schadendorf, MD, University Hospital, Essen

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): June 4, 2024
• Study Completion (Actual): June 4, 2024

Study Registration Dates

• First Submitted: March 10, 2021
• First Submitted That Met QC Criteria: March 21, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: metastatic; locally advanced; cSCC
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Complement Inactivating Agents; Vilobelimab; Pembrolizumab
• Other Study ID Numbers: IFX-1 P2.8; MK-3475-A93 (Other Identifier: Merck Sharp & Dohme LLC); KEYNOTE-A93 (Other Identifier: Merck Sharp & Dohme LLC); 2020-000864-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No