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

NCT04812535 | Terminated Phase 2 Results FDA Drug

• 4 other identifiers: IFX-1 P2.8MK-3475-A93KEYNOTE-A932020-000864-42
• Study Type: interventional
• Target: 30
• Locations: 5 countries
• Sites: 25

Brief Summary

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

Conditions

SCC - Squamous Cell Carcinoma of Skin

Keywords

cSCC; metastatic; locally advanced

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Disease Control Rate - Arm A and Arm B

  Up to 36 months

• Progression-free Survival (PFS)- Arm A and Arm B

  Up to 36 months

• Overall Survival (OS)- Arm A and Arm B

  Up to 36 months

• Antidrug Antibodies (ADAs) - Arm A and Arm B

  Up to 27 months

• Quality of Life (QoL) - Arm A and Arm B

  Up to 36 months

Study Arms (4)

Arm A:

EXPERIMENTAL

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

Arm B: Regimen 1:

EXPERIMENTAL

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

Arm B: Regimen 2:

EXPERIMENTAL

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

Arm B: Regimen 3:

EXPERIMENTAL

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

Interventions

Vilobelimab DRUG

Vilobelimab Monotherapy

Arm A:

Vilobelimab + pembrolizumab combination therapy DRUG

Vilobelimab + pembrolizumab combination therapy

Also known as: KEYTRUDA®

Arm B: Regimen 1:; Arm B: Regimen 2:; Arm B: Regimen 3:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Has received ≥2 doses of an anti-PD-1/L1 mAb that has been approved for treatment of cSCC or any solid tumor
• 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.
• 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.
• 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)
• For Stage 2 patients only: on Cycle 2 Day 1 (±3 days) (mandatory)
• 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)
• 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:
• ≥4 weeks for mAbs, systemic cytotoxic anticancer therapy, treatment with other anticancer investigational agents
• ≥3 weeks for local radiation therapy
• Eastern Cooperative Oncology Group performance status (ECOG PS) status of ≤1

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• InflaRx GmbH: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (25)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Orlando Health, Inc.

Orlando, Florida, 32806, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

University Hospital Antwerp (UZA)

Edegem, 2650, Belgium

Location

St. Augustinus Hospital

Wilrijk, 2610, Belgium

Location

University Hospital Center of Grenoble Alpes, Department of Dermatology

Grenoble, 38700, France

Location

South Lyon Hospital Center

Lyon, 69495, France

Location

CHU APHM la Timone / Aix Marseille University, Dermatology and Skin Cancer Department

Marseille, 13385, France

Location

St. Louis Hospital

Paris, 75010, France

Location

University Hospital Center of Poitiers, Department of Oncology

Poitiers, 86021, France

Location

University Hospital Erlangen, Department of Dermatology

Erlangen, 91054, Germany

Location

University Duisburg-Essen, University Hospital Essen, Department of Dermatology

Essen, 45147, Germany

Location

Frankfurt University Clinic, Department of Dermatology, Venereology and Allergology

Frankfurt, 60590, Germany

Location

University Hospital Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

University Hospital Leipzig, Department of Dermatology, Venereology and Allergology

Leipzig, 04103, Germany

Location

University Hospital Regensburg, Clinic and Policlinic for Dermatology

Regensburg, 93053, Germany

Location

University Hospital Tuebingen, Department of Dermatology

Tübingen, 72076, Germany

Location

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

ICO Hospitalet

Barcelona, 08908, Spain

Location

MD Anderson International Cancer Center Spain

Madrid, 28033, Spain

Location

Regional University Hospital of Malaga

Málaga, 29010, Spain

Location

University Clinical Hospital of Salamanca

Salamanca, 37007, Spain

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

vilobelimab; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was prematurely terminated due to a strategic decision by the sponsor. Therefore, the total number of participants enrolled is smaller than planned (actually enrolled and treated: 25, planned: 70).

Results Point of Contact

• Title: Dr. Camilla Chong, CMO
• Organization: InflaRx GmbH

camilla.chong@inflarx.com

+49 3641-508-180

Study Officials

• Prof. Dr. D. Schadendorf, MD

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Arm A: Vilobelimab monotherapy; Arm B: Vilobelimab + in combination with approved dosing scheme of pembrolizumab

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 23, 2021
• Study Start: March 31, 2021
• Primary Completion: June 4, 2024
• Study Completion: June 4, 2024
• Last Updated: February 11, 2025
• Results First Posted: February 11, 2025

Record last verified: 2025-01

Locations

BE (2); DE (7); FR (5); ES (5); US (6)