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

• ClinicalTrials.gov Identifier: NCT05256381
• Recruitment Status: Active, not recruiting
• First Posted: February 25, 2022
• Last Update Posted: March 8, 2024
• Sponsor: SOTIO Biotech AG
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Sotio Biotech Inc. ( SOTIO Biotech AG )

Tracking Information

• First Submitted Date: February 8, 2022
• First Posted Date: February 25, 2022
• Last Update Posted Date: March 8, 2024
• Actual Study Start Date: June 21, 2022
• Estimated Primary Completion Date: April 1, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 24, 2022): Objective Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Day 1 up to approximately 3 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 6, 2024)

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

Original Secondary Outcome Measures (submitted: February 24, 2022)

• Number of Participants with a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Day 1 up to approximately 3 years ]
• Number of Participants with an Adverse Event of Special Interest (AESI) [ Time Frame: Day 1 up to approximately 3 years ]
• Immune ORR (iORR) According to RECIST for immune-based therapeutics (iRECIST) [ Time Frame: Day 1 up to approximately 3 years ]
• Best Overall Response (BOR) According to RECIST 1.1 [ Time Frame: Day 1 up to approximately 3 years ]
• Immune BOR (iBOR) According to iRECIST [ Time Frame: Day 1 up to approximately 3 years ]
• Duration of Response (DoR) According to RECIST 1.1 [ Time Frame: Day 1 up to approximately 3 years ]
• Immune DoR (iDoR) According to iRECIST [ Time Frame: Day 1 up to approximately 3 years ]
• Clinical Benefit Rate (CBR) According to RECIST 1.1 [ Time Frame: Day 1 up to approximately 3 years ]
• Immune CBR (iCBR) According to iRECIST [ Time Frame: Day 1 up to approximately 3 years ]
• Progression-free Survival (PFS) According to RECIST 1.1 [ Time Frame: Day 1 up to approximately 3 years ]
• Immune PFS (iPFS) According to iRECIST [ Time Frame: Day 1 up to approximately 3 years ]
• Time to Response (TtR) According to RECIST 1.1 [ Time Frame: Day 1 up to approximately 3 years ]
• Immune TtR (iTtR) According to iRECIST [ Time Frame: 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 [ Time Frame: Day 1 up to approximately 3 years ]
• mCRPC only: CBR as Assessed According to PCWG3-modified RECIST 1.1 [ Time Frame: Day 1 up to approximately 3 years ]
• mCRPC only: PFS as Assessed According to PCWG3-modified RECIST 1.1 [ Time Frame: Day 1 up to approximately 3 years ]
• mCRPC only: Circulating Tumor Cell (CTC) Count Conversion as Assessed According to PCWG3-modified RECIST 1.1 [ Time Frame: 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 [ Time Frame: Day 1 up to approximately 2 years ]
• mCRPC only: Time to Confirmed PSA Progression as Assessed According to PCWG3-modified RECIST 1.1 [ Time Frame: Day 1 up to approximately 2 years ]
• SOT101 Plasma Concentration Profile at Various Timepoints [ Time Frame: Cycle 1 Day 1 to Cycle 3 Day 1 (up to approximately 9 weeks, where each cycle is 3 weeks) ]
• Number of Participants with Anti-drug Antibodies (ADAs) [ Time Frame: Day 1 up to approximately 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer
• Colorectal Cancer
• Cutaneous Squamous Cell Carcinoma
• Hepatocellular Carcinoma
• Castration-resistant Prostate Cancer
• Ovarian Cancer

Intervention

• Drug: Nanrilkefusp Alfa
  Subcutaneous (SC) injection.
  Other Name: SOT101
• Drug: Pembrolizumab
  Intravenous (IV) infusion via peripheral or central venous line.
  Other Name: KEYTRUDA®

Study Arms

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.

Interventions:

• Drug: Nanrilkefusp Alfa
• Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 24, 2022): 320
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 30, 2025
• Estimated Primary Completion Date: April 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, France, Georgia, Hungary, Italy, Poland, Spain, United States

Administrative Information

• NCT Number: NCT05256381
• 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sotio Biotech Inc. ( SOTIO Biotech AG )
• Original Responsible Party: Same as current
• Current Study Sponsor: SOTIO Biotech AG
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: Sotio Biotech Inc.
• Verification Date: September 2023