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

A Phase 2, Open-label, Single-arm, Multicenter Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced/Refractory Solid Tumors

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

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma; Colorectal Cancer; Ovarian Cancer; Non-Small Cell Lung Cancer; Castration-resistant Prostate Cancer; Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Nanrilkefusp Alfa

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Richard Kapsa; Phone Number: (+420) 2241 74448; Email: kapsa@sotio.com

Study Locations

• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Charleroi, Belgium, 6000
    • Grand Hospital de Charleroi
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv onkologicky ustav
  • Hořovice, Czechia, 268 31
    • Nemocnice Horovice
  • Olomouc, Czechia, 77900
    • Fakultní Nemocnice Olomouc
• France
  • Boulogne-Billancourt, France, 92100
    • Hôpital Ambroise-Paré
  • Bourdeaux, France, 33000
    • Merchant Logo Institute Bergonié
  • Caen, France, 14076
    • Centre de Lutte Contre le Cancer
  • Marseille, France, 13005
    • Hospital del la Timone
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Nice, France, 06202
    • Hospital L'archet
  • Suresnes, France, 92150
    • Hopital FOCH
  • Toulouse, France, 31059
    • Institute Claudius Regaud
  • Villejuif, France, 94805
    • Gustave Roussy
• Georgia
  • Batumi, Georgia, 6000
    • High Technology Hospital MedCenter Ltd - Batumi
  • Kutaisi, Georgia, 4600
    • Evex Hospitals- Kutaisi Referral
  • Tbilisi, Georgia, 0167
    • Jerarsi Clinic
  • Tbilisi, Georgia, 0159
    • Evex Hospitals - Caraps Medline
  • Tbilisi, Georgia, 0186
    • Consilium Medulla Multiprofile Clinic
  • Tbilisi, Georgia, 0159
    • New Vision University Hospital
  • Tbilisi, Georgia, 0112
    • LLC Todua Clinic
  • Tbilisi, Georgia, 0160
    • Tbilisi Institute of Medicine
  • Tbilisi, Georgia, 0186
    • Evex Hospitals - Caucasus Medical Center
• Hungary
  • Budapest, Hungary, 1134
    • Eszak-Pesti Centrumkorhaz - Honvedkorhaz
  • Győr, Hungary, 9023
    • Petz Aladár Egyetemi Oktató Kórház - Győr
• Italy
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia
  • Meldola, Italy, 47014
    • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
  • Napoli, Italy, 80131
    • Instituto Nazionale Tumori IRCCS Fondazione G. Pascale
  • Piacenza, Italy, 29121
    • Ospedale Guglielmo da Saliceto
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese - L'ospedale Santa Maria alle Scotte
  • Sondrio, Italy, 23100
    • Ospedale Civile Di Sondrio
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria integrata Verona
• Poland
  • Skorzewo, Poland, 60-185
    • Pratia Poznan
  • Warszawa, Poland, 02-172
    • MTZ Clinical Research Powered by Pratia
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-780
      • Uniwersytecki Szpital Kliniczny w Poznaniu
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera - Materno Infantil
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08908
    • Institut Catala d'Oncologia
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra - Madrid
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra - Pamplona
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United States
  • California
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburg Medical Center (UPMC) Hillman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nanrilkefusp Alfa and 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.	Drug: Pembrolizumab; Intravenous (IV) infusion via peripheral or central venous line.; Other Names: KEYTRUDA®; Drug: Nanrilkefusp Alfa; Subcutaneous (SC) injection.; Other Names: SOT101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Number of Participants with a Treatment-emergent Adverse Event (TEAE)	Day 1 up to approximately 3 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
Best Overall Response (BOR) According to RECIST 1.1	Day 1 up to approximately 3 years
Immune BOR (iBOR) According to 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
Clinical Benefit Rate (CBR) According to RECIST 1.1	Day 1 up to approximately 3 years
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
Immune PFS (iPFS) According to iRECIST	Day 1 up to approximately 3 years
Time to Response (TtR) 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
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: CBR as Assessed According to PCWG3-modified RECIST 1.1	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
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: Confirmed Prostate-specific Antigen (PSA) Decline of ≥50% 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 Anti-drug Antibodies (ADAs)	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)

Collaborators and Investigators

• Sponsor: SOTIO Biotech AG
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Pembrolizumab; Colorectal Cancer; Ovarian Cancer; SOT101; SO-C101; Advanced Hepatocellular Carcinoma; Cutaneous Squamous Cell Carcinoma; Metastatic Castration-resistant Prostate Cancer; KEYNOTE-D13; AURELIO-04; Nanrilkefusp Alfa
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Liver Diseases; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Liver Neoplasms; Intestinal Neoplasms; Rectal Diseases; Lung Neoplasms; Neoplasms, Squamous Cell; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Genital Diseases, Female; Prostatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Carcinoma, Hepatocellular; Colorectal Neoplasms; Ovarian Neoplasms; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: SC104; KEYNOTE-D13 (Other Identifier: Merck Sharp & Dohme); AURELIO-04 (Other Identifier: SOTIO Biotech AG); 2021-005774-25 (EudraCT Number); MK-3475-D13 (Other Identifier: Merck Sharp & Dohme)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No