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SCC - Squamous Cell Carcinoma of SkinPhase 2NCT04812535

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

A Phase 2 study testing Vilobelimab and Vilobelimab + pembrolizumab combination therapy in people with SCC - Squamous Cell Carcinoma of Skin, run by InflaRx GmbH at 25 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
SCC - Squamous Cell Carcinoma of Skin
What is being tested?
Vilobelimab and Vilobelimab + pembrolizumab combination therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
25 sitesin 5 countries
Study dates
31 Mar 2021to 4 Jun 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 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
  • Adequate organ function
  • Patient (or legally acceptable representative if applicable) provides written informed consent for the study.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

25 sites in 5 countries.

25 sites in 5 countries

Germany7 sites
  • University Hospital Erlangen, Department of Dermatology

    Erlangen, 91054

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

    Essen, 45147

  • Frankfurt University Clinic, Department of Dermatology, Venereology and Allergology

    Frankfurt, 60590

  • University Hospital Hamburg-Eppendorf

    Hamburg, 20246

  • University Hospital Leipzig, Department of Dermatology, Venereology and Allergology

    Leipzig, 04103

  • University Hospital Regensburg, Clinic and Policlinic for Dermatology

    Regensburg, 93053

  • University Hospital Tuebingen, Department of Dermatology

    Tübingen, 72076

Other trials in Germany

United States6 sites
  • Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Orlando Health, Inc.

    Orlando, Florida, 32806

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

France5 sites
  • University Hospital Center of Grenoble Alpes, Department of Dermatology

    Grenoble, 38700

  • South Lyon Hospital Center

    Lyon, 69495

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

    Marseille, 13385

  • St. Louis Hospital

    Paris, 75010

  • University Hospital Center of Poitiers, Department of Oncology

    Poitiers, 86021

Other trials in France

Spain5 sites
  • University Hospital Vall d'Hebron

    Barcelona, 08035

  • ICO Hospitalet

    Barcelona, 08908

  • MD Anderson International Cancer Center Spain

    Madrid, 28033

  • Regional University Hospital of Malaga

    Málaga, 29010

  • University Clinical Hospital of Salamanca

    Salamanca, 37007

Other trials in Spain

Belgium2 sites
  • University Hospital Antwerp (UZA)

    Edegem, 2650

  • St. Augustinus Hospital

    Wilrijk, 2610

Other trials in Belgium

About this study

Official title: 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

Read the 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.

Being tested
Vilobelimab, Vilobelimab + pembrolizumab combination therapy
Keywords
cSCC, metastatic, locally advanced
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VilobelimabDrug

    Vilobelimab Monotherapy

  • Vilobelimab + pembrolizumab combination therapyDrug

    Also called KEYTRUDA®

    Vilobelimab + pembrolizumab combination therapy

Study groups in NCT04812535
Study groupRoleWhat they receive
Arm A:ExperimentalVilobelimab 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)
Receives: Drug: Vilobelimab
Arm B: Regimen 1:ExperimentalVilobelimab + 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
Receives: Drug: Vilobelimab + pembrolizumab combination therapy
Arm B: Regimen 2:ExperimentalVilobelimab + 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
Receives: Drug: Vilobelimab + pembrolizumab combination therapy
Arm B: Regimen 3:ExperimentalVilobelimab + 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
Receives: Drug: Vilobelimab + pembrolizumab combination therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 36 months

  2. Dose-limiting Toxicity (DLT) - Arm B

    Frequency of dose-limiting toxicities (DLTs) by dose cohort.

    Measured: Cycle 1 Day 1 - Cycle 1 Day 36

Secondary outcomes (7)
  1. 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.

    Measured: Up to 36 months

  2. 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.

    Measured: Up to 36 months

  3. 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.

    Measured: Up to 36 months

  4. 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.

    Measured: Up to 27 months

  5. 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.

    Measured: Up to 36 months

  6. 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.

    Measured: Up to 36 months

  7. 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.

    Measured: Up to 27 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2021
  2. Study start31 Mar 2021
  3. Primary completion4 Jun 2024
  4. Study completion4 Jun 2024

Why it stopped: Sponsor decided to stop the development of vilobelimab in cSCC and early terminated the IFX-1-P2.8 trial due to new alternative treatments for cSCC with high efficacy rates.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Arm A: Vilobelimab monotherapy; Arm B: Vilobelimab + in combination with approved dosing scheme of pembrolizumab
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04812535
Sponsor's protocol ID
IFX-1 P2.8
Other IDs
MK-3475-A93, KEYNOTE-A93, 2020-000864-42
Status last verified
Jan 2025
First submitted
10 Mar 2021
Last updated
11 Feb 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vilobelimab and Vilobelimab + pembrolizumab combination therapy in people with SCC - Squamous Cell Carcinoma of Skin, run by InflaRx GmbH at 25 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Germany, United States, France, Spain, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best Overall Response Rate (Best ORR) - Arm A and Arm B (time frame: Up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2025.

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