A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Setanaxib, When Administered With Pembrolizumab, in Patients With Recurrent or Metastatic SCCHN

Calliditas Therapeutics Suisse SA24 sites in 7 countries55 target enrollmentApril 6, 2022

ConditionsSquamous Cell Carcinoma of Head and Neck

InterventionsSetanaxib Pembrolizumab Placebo

DrugsPlacebo

Overview

Phase: Phase 2
Intervention: Setanaxib
Conditions: Squamous Cell Carcinoma of Head and Neck
Sponsor: Calliditas Therapeutics Suisse SA
Enrollment: 55
Locations: 24
Primary Endpoint: Best Percentage Change in Tumour Size
Status: Completed
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of this study is to compare the change in tumour size per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab.

Registry

clinicaltrials.gov

Start Date

April 6, 2022

End Date

August 21, 2025

Last Updated

8 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Calliditas Therapeutics Suisse SA

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female patients aged ≥18 years, inclusive, at the time of informed consent.
•Willing and able to give informed consent and to comply with the requirements of the study.
•Histologically- or cytologically-confirmed diagnosis of SCCHN that is recurrent or metastatic with or without nodal involvement, and with or without metastatic spread, and is not eligible for surgical resection.
•Candidates for first-line treatment for pembrolizumab for recurrent or metastatic SCCHN, at the discretion of the investigator.
•A positive CAFs level (defined as CAFs level in tumours ≥5%), performed at a central laboratory, with fresh tumour biopsy taken during or within 30 days prior to the Screening Period. If available, suitable archival tissue (taken within 6 months prior to the Screening Visit and where the patient has received no further anti-cancer therapy during this 6-month period) can be used to assess tumour CAFs level and determine patient eligibility.
•Measurable disease, in accordance with RECIST v1.1, and with tumour accessible and of sufficient volume for pre-treatment and on-treatment biopsy.
•Combined positive score (CPS) ≥1, as determined on the archival or fresh tumour biopsy taken during or within 30 days prior to the Screening Period.
•HPV status known at randomisation.
•Life expectancy of at least 6 months in the judgment of the investigator.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or

Exclusion Criteria

•Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed.
•Anti-cancer mAb treatment within 4 weeks prior to study Day
•Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 (radiation therapy can be allowed for palliative therapy of bone metastasis only).
•Not recovered from AEs Grade 2 or greater (except for alopecia) due to previously administered agents.
•Treatment with any investigational agent within 12 weeks of Screening Visit or 5 half-lives of the IMP (if known), whichever is longer, or current enrolment in an interventional clinical study.
•Prior treatment with setanaxib or participation in a previous setanaxib clinical study.
•Prior treatment with pembrolizumab.
•Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer that has undergone potentially curative therapy, or malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of IMP and of low potential risk for recurrence.
•Known active central nervous system metastases and/or carcinomatous meningitis.
•Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents. The following are exceptions to this criterion:

Arms & Interventions

Setanaxib 1600 mg and Pembrolizumab 200 mg

Participants will be administered setanaxib at a dose of 1600 mg/day for the up to 24-month double-blind treatment period. Participants will also be administered Pembrolizumab 200 mg intravenously every 3 weeks.

Intervention: Setanaxib

Setanaxib 1600 mg and Pembrolizumab 200 mg

Intervention: Pembrolizumab

Placebo and Pembrolizumab 200 mg

Participants will be administered placebo for the up to 24-month double-blind treatment period. Participants will also be administered Pembrolizumab 200 mg intravenously every 3 weeks.

Intervention: Pembrolizumab

Placebo and Pembrolizumab 200 mg

Participants will be administered placebo for the up to 24-month double-blind treatment period. Participants will also be administered Pembrolizumab 200 mg intravenously every 3 weeks.

Intervention: Placebo

Outcomes

Primary Outcomes

Best Percentage Change in Tumour Size

Time Frame: Baseline to at least 15 weeks and up to 51 weeks

Defined as the best percentage change from Baseline in the sum of diameters of target lesions, as assessed by RECIST v1.1.

Secondary Outcomes

Maximum Plasma Concentration at Steady State (Cmax-ss) of GKT138184(Baseline up to approximately 26 months)
Change From Baseline in Cancer-associated Fibroblasts (CAFs) Level in Tumour Tissue(Baseline up to approximately 9 weeks)
Progression Free Survival (PFS)(Baseline up to approximately 21 months)
Change From Baseline in the Number of Cluster of Differentiation 8 (CD8+) Tumour Infiltrating Lymphocytes (TILs) in Tumour Tissue(Baseline up to approximately 9 weeks)
Change From Baseline in the Number of Regulatory T-cells in Tumour Tissue(Baseline up to approximately 9 weeks)
Overall Response Rate (ORR)(Baseline up to approximately 12 months)
Duration of Response (DoR)(Baseline up to approximately 12 months)
Disease Control Rate (DCR)(Baseline up to approximately 12 months)
Overall Survival (OS)(Baseline up to 12 months)
Number of Participants With Adverse Events (AEs)(Baseline up to approximately 21 months)
Number of Participants With Adverse Events of Special Interest (AESI)(Baseline up to approximately 21 months)
Levels of Programmed Death-ligand 1 (PD-L1) Expression in Tumour Tissue(Baseline up to approximately 9 weeks)
Change From Baseline in CAFs Cell Type Abundance Based on Gene Expression Profiles(Baseline up to approximately 9 weeks)
Change From Baseline in CD8+ TILs Cell Type Abundance Based on Gene Expression Profiles(Baseline up to approximately 9 weeks)
Change From Baseline in Regulatory T-cell Abundance Based on Gene Expression Profiles(Baseline up to approximately 9 weeks)
Area Under The Concentration-time Curve Over a 24-hour Period at Steady State (AUC[0-24]-ss) of Setanaxib(Baseline, Week 3, week 9, week 24, week 51)
Area Under The Concentration-time Curve Over a 24-hour Period at Steady State (AUC24-ss) of GKT138184(Baseline, Week 3, week 9, week 24, week 51)
Minimum Plasma Concentration at Steady State (Cmax-ss) of Setanaxib(Baseline, Week 3, week 9, week 24, week 51)
Minimum Plasma Concentration at Steady State (Cmin-ss) of GKT138184(Baseline, Week 3, week 9, week 24, week 51)
Maximum Plasma Concentration at Steady State (Cmax-ss) of Setanaxib(Baseline, Week 3, week 9, week 24, week 51)