Clinical trial NCT04812535: Non-comparative Study of IFX-1 Alone or IFX-1+Pembrolizumab in Patients With Locally Advanced or Metastatic cSCC.
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: SCC - Squamous Cell Carcinoma of Skin
Keywords: cSCC
metastatic
locally advanced
Lead sponsor: InflaRx GmbH
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-03-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm A: Vilobelimab monotherapy; Arm B: Vilobelimab + in combination with approved dosing scheme of pembrolizumab
Primary purpose: TREATMENT

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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Best Overall Response Rate (Best ORR) - Arm A and Arm B
timeFrame: Up to 36 months
measure: Dose-limiting Toxicity (DLT) - Arm B
timeFrame: Cycle 1 Day 1 - Cycle 1 Day 36
Secondary outcomes:
measure: Disease Control Rate - Arm A and Arm B
timeFrame: Up to 36 months
measure: Progression-free Survival (PFS)- Arm A and Arm B
timeFrame: Up to 36 months
measure: Overall Survival (OS)- Arm A and Arm B
timeFrame: Up to 36 months
measure: Antidrug Antibodies (ADAs) - Arm A and Arm B
timeFrame: Up to 27 months
measure: Quality of Life (QoL) - Arm A and Arm B
timeFrame: Up to 36 months
measure: 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
timeFrame: Up to 36 months
measure: Plasma Concentration of Vilobelimab - Arm A and Arm B
timeFrame: Up to 27 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion
state: Colorado
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Edegem
country: Belgium
facility: University Hospital Antwerp (UZA)
city: Wilrijk
country: Belgium
facility: St. Augustinus Hospital
city: Grenoble
country: France
facility: University Hospital Center of Grenoble Alpes, Department of Dermatology
city: Lyon
country: France
facility: South Lyon Hospital Center
city: Marseille
country: France
facility: CHU APHM la Timone / Aix Marseille University, Dermatology and Skin Cancer Department
city: Paris
country: France
facility: St. Louis Hospital
city: Poitiers
country: France
facility: University Hospital Center of Poitiers, Department of Oncology
city: Erlangen
country: Germany
facility: University Hospital Erlangen, Department of Dermatology
city: Essen
country: Germany
facility: University Duisburg-Essen, University Hospital Essen, Department of Dermatology
city: Frankfurt
country: Germany
facility: Frankfurt University Clinic, Department of Dermatology, Venereology and Allergology
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
city: Leipzig
country: Germany
facility: University Hospital Leipzig, Department of Dermatology, Venereology and Allergology
city: Regensburg
country: Germany
facility: University Hospital Regensburg, Clinic and Policlinic for Dermatology
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen, Department of Dermatology
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: ICO Hospitalet
city: Madrid
country: Spain
facility: MD Anderson International Cancer Center Spain
city: Málaga
country: Spain
facility: Regional University Hospital of Malaga
city: Salamanca
country: Spain
facility: University Clinical Hospital of Salamanca
Study officials:
affiliation: University Hospital, Essen
name: Prof. Dr. D. Schadendorf, MD
role: PRINCIPAL_INVESTIGATOR
References: