A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors

Phase 2

Terminated

• Conditions: Colorectal Cancer; Castration-resistant Prostate Cancer; Ovarian Cancer; Hepatocellular Carcinoma; Non-Small Cell Lung Cancer; Cutaneous Squamous Cell Carcinoma
• Interventions: Drug: Nanrilkefusp Alfa; Drug: Pembrolizumab

• Registration Number: NCT05256381
• Lead Sponsor: SOTIO Biotech AG

Brief Summary

The primary objective of the study is to estimate the antitumor efficacy of nanrilkefusp alfa in combination with pembrolizumab in selected tumors.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-08
• Study First Submitted QC: 2022-02-24
• Study First Posted: 2022-02-25
• Study Start: 2022-06-21
• Primary Completion: 2024-08-31
• Status Verified: 2024-10
• Study Completion: 2024-11-29
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 166

Inclusion Criteria

• Participants with the following histologically or cytologically confirmed solid tumor indications and line of treatment:

  1. Non-small cell lung cancer (NSCLC).
  2. Colorectal cancer.
  3. Cutaneous squamous cell carcinoma (cSCC).
  4. Advanced hepatocellular carcinoma (not applicable in France).
  5. mCRPC.
  6. Ovarian cancer.

• Have measurable disease per RECIST 1.1. mCRPC participants with no measurable disease and only widespread bone disease must have a CTC count of ≥5 cells per 7.5 mL of blood.

• Availability of tumor tissue from a fresh biopsy at screening unless the biopsy cannot be obtained due to safety reasons or non-accessibility of the tumor site. If it is not possible to obtain a fresh biopsy, every effort should be taken to retrieve an archival biopsy. Archived, fixed tumor tissue may only be collected if taken preferentially after completion of the most recent systemic tumor therapy and within 12 months prior to the first dose of study treatment.

• Eastern Cooperative Oncology Group (ECOG) score 0-1.

• Have recovered from all AEs (except alopecia) due to previous therapies to grade ≤1 (excluding alopecia) or have stable grade 2 neuropathy.

• Have adequate organ function as defined below:

  1. Hematology:

     1. Absolute neutrophil count ≥1500/μL.
     2. Platelets ≥100 000/μL.
     3. Hemoglobin ≥9.0 g/dL .

  2. Renal function: Creatinine clearance as measured by glomerular filtration rate ≥30 mL/min using Cockcroft-Gault equation.

  3. Hepatic function: Alanine transaminase (ALT)/aspartate transaminase (AST) ≤2.5× upper limit of normal (ULN) and total bilirubin ≤1.5×ULN or direct bilirubin ≤ ULN in participants without liver metastasis. In participants with liver metastasis, ALT/AST ≤5×ULN is allowed but total bilirubin must be ≤2×ULN.

  4. Prothrombin time and activated partial thromboplastin time ≤1.5×ULN.

• Participants must not have active hepatitis B or hepatitis C infection.

• Adequate contraception must be applied in all women of childbearing potential (WOCBP) and in male participants.

Exclusion Criteria

• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a grade ≥3 AE.

• Prior exposure to agonists of interleukin (IL)-2 or IL-15.

• Prior systemic anti-cancer therapies, including investigational agents:

  1. Less than 4 weeks for systemic chemotherapy and immuno-oncology therapies; and for tyrosine kinase inhibitors 4 weeks or 5 half-lives (whichever is shorter).
  2. Less than 4 weeks from major surgeries and not recovered adequately.

• Has received prior radiotherapy within 2 weeks of the start of study interventions or have had a history of radiation pneumonitis.

• NSCLC indication only: Received radiation therapy to the lung >30 Gy within 6 months.

• Has received a live or live-attenuated vaccine within 30 days.

• Clinically significant cardiac abnormalities including prior history of any of the following:

  1. Cardiomyopathy, with left ventricular ejection fraction ≤ 50%.
  2. Congestive heart failure of New York Heart Association grade ≥2.
  3. History of clinically significant artery or coronary heart disease.
  4. Prolongation of QTcF >450 msec .
  5. Clinically significant cardiac arrythmia that cannot be controlled with adequate medication.

• Uncontrolled hypertension defined as systolic blood pressure >160 mmHg, diastolic blood pressure >110 mmHg.

• Prior allogeneic hematopoietic stem cell transplantation within the last 5 years.

• Prior allogeneic tissue/solid organ transplant.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy.

• History of or serology positive for human immunodeficiency virus (HIV).

• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years, except for basal cell carcinoma of the skin or carcinoma in situ that have undergone potentially curative therapy are not excluded.

• Has known active central nervous system metastases and/or carcinomatous meningitis, unless stable.

• Had severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of its excipients.

• Has an active autoimmune disease that has required systemic treatment in the past 2 years.

• History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.

• Has an active infection requiring systemic therapy.

• Has any condition that might confound the results of the study or interfere with the participant's participation for the full duration of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nanrilkefusp Alfa and Pembrolizumab	Pembrolizumab	Participants will be treated with 12 μg/kg of nanrilkefusp alfa on Day 1, Day 2, Day 8, and Day 9 of each 3-week cycle in combination with 200 mg pembrolizumab on Day 1 of each 3-week cycle.
Nanrilkefusp Alfa and Pembrolizumab	Nanrilkefusp Alfa	Participants will be treated with 12 μg/kg of nanrilkefusp alfa on Day 1, Day 2, Day 8, and Day 9 of each 3-week cycle in combination with 200 mg pembrolizumab on Day 1 of each 3-week cycle.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)	Day 1 up to approximately 3 years

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Anti-drug Antibodies (ADAs)	Day 1 up to approximately 2 years
Number of Participants with a Treatment-emergent Adverse Event (TEAE)	Day 1 up to approximately 3 years
Best Overall Response (BOR) According to RECIST 1.1	Day 1 up to approximately 3 years
Time to Response (TtR) According to RECIST 1.1	Day 1 up to approximately 3 years
Metastatic Castration-resistant Prostate Cancer (mCRPC) only: DoR as Assessed According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified RECIST 1.1	Day 1 up to approximately 3 years
mCRPC only: Confirmed Prostate-specific Antigen (PSA) Decline of ≥50% as Assessed According to PCWG3-modified RECIST 1.1	Day 1 up to approximately 2 years
Nanrilkefusp Alfa Concentration Profile at Various Timepoints	Cycle 1 Day 1 to Cycle 3 Day 1 (up to approximately 9 weeks, where each cycle is 3 weeks)
Immune CBR (iCBR) According to iRECIST	Day 1 up to approximately 3 years
Progression-free Survival (PFS) According to RECIST 1.1	Day 1 up to approximately 3 years
mCRPC only: Circulating Tumor Cell (CTC) Count Conversion as Assessed According to PCWG3-modified RECIST 1.1	Day 1 up to approximately 2 years
mCRPC only: Time to Confirmed PSA Progression as Assessed According to PCWG3-modified RECIST 1.1	Day 1 up to approximately 2 years
Number of Participants with an Adverse Event of Special Interest (AESI)	Day 1 up to approximately 3 years
Immune ORR (iORR) According to RECIST for immune-based therapeutics (iRECIST)	Day 1 up to approximately 3 years
Duration of Response (DoR) According to RECIST 1.1	Day 1 up to approximately 3 years
Immune DoR (iDoR) According to iRECIST	Day 1 up to approximately 3 years
Immune PFS (iPFS) According to iRECIST	Day 1 up to approximately 3 years
mCRPC only: PFS as Assessed According to PCWG3-modified RECIST 1.1	Day 1 up to approximately 3 years
Clinical Benefit Rate (CBR) According to RECIST 1.1	Day 1 up to approximately 3 years
Immune TtR (iTtR) According to iRECIST	Day 1 up to approximately 3 years
mCRPC only: CBR as Assessed According to PCWG3-modified RECIST 1.1	Day 1 up to approximately 3 years
Immune BOR (iBOR) According to iRECIST	Day 1 up to approximately 3 years

Trial Locations

Locations (54)

Evex Hospitals - Caraps Medline; 🇬🇪 Tbilisi, Georgia

Institut Jules Bordet; 🇧🇪 Anderlecht, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Universitair Ziekenhuis Leuven - Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Centre Hospitalier Universitaire de Liège; 🇧🇪 Liège, Belgium

High Technology Hospital MedCenter Ltd - Batumi; 🇬🇪 Batumi, Georgia

Petz Aladár Egyetemi Oktató Kórház - Győr; 🇭🇺 Győr, Hungary

MTZ Clinical Research powered by Pratia; 🇵🇱 Warszawa, Poland

Észak-Pesti Centrumkórház - Honvédkórház; 🇭🇺 Budapest, Hungary

Tbilisi Institute of Medicine; 🇬🇪 Tbilisi, Georgia

Pratia Poznań; 🇵🇱 Skorzewo, Poland

Evex Hospitals- Kutaisi Referral; 🇬🇪 Kutaisi, Georgia

Jerarsi Clinic; 🇬🇪 Tbilisi, Georgia

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST; 🇮🇹 Meldola, Italy

Instituto Nazionale Tumori IRCCS Fondazione G. Pascale; 🇮🇹 Napoli, Italy

Ospedale Civile di Sondrio; 🇮🇹 Sondrio, Italy

Institut Universitaire du Cancer de Toulouse Oncopole; 🇫🇷 Toulouse, France

New Vision University Hospital; 🇬🇪 Tbilisi, Georgia

Hospital del la Timone; 🇫🇷 Marseille, France

Innovative Clinical Research Institute; 🇺🇸 Whittier, California, United States

University of Pittsburg Medical Center (UPMC) Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Grand Hospital de Charleroi; 🇧🇪 Charleroi, Belgium

Nemocnice Hořovice; 🇨🇿 Hořovice, Czechia

Masarykuv Onkologicky Ustav; 🇨🇿 Brno, Czechia

Fakultní nemocnice Olomouc; 🇨🇿 Olomouc, Czechia

Hôpital Ambroise-Paré; 🇫🇷 Boulogne-Billancourt, France

Merchant Logo Institute Bergonié; 🇫🇷 Bourdeaux, France

Centre de Lutte Contre le Cancer; 🇫🇷 Caen, France

Centre Francois Baclesser; 🇫🇷 Caen, France

Centre Hospitalier Universitaire de Nantes; 🇫🇷 Nantes, France

Hospital L'archet; 🇫🇷 Nice, France

Hôpital Foch; 🇫🇷 Suresnes, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Institute Claudius Regaud; 🇫🇷 Toulouse, France

Gustave Roussy; 🇫🇷 Villejuif, France

LLC Todua Clinic; 🇬🇪 Tbilisi, Georgia

Consilium Medulla Multiprofile Clinic; 🇬🇪 Tbilisi, Georgia

Evex Hospitals - Caucasus Medical Center; 🇬🇪 Tbilisi, Georgia

Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

Ospedale Guglielmo da Saliceto; 🇮🇹 Piacenza, Italy

Fondazione Policlinico Universitario Agostino Gemelli; 🇮🇹 Rome, Italy

Azienda Ospedaliera Universitaria Senese - L'ospedale Santa Maria alle Scotte; 🇮🇹 Siena, Italy

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Uniwersytecki Szpital Kliniczny w Poznaniu; 🇵🇱 Poznań, Wielkopolskie, Poland

Azienda Ospedaliera Universitaria Integrata Verona; 🇮🇹 Verona, Italy

Hospital Teresa Herrera - Materno Infantil; 🇪🇸 A Coruña, Spain

Hospital Universitari Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Institut Catala d'Oncologia; 🇪🇸 Barcelona, Spain

Clinica Universidad de Navarra - Pamplona; 🇪🇸 Madrid, Spain

Clínica Universidad de Navarra - Madrid; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro - Majadahonda; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain