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

SOTIO

Status and phase: Active, not recruiting; Phase 2

Conditions: Cutaneous Squamous Cell Carcinoma; Castration-resistant Prostate Cancer; Hepatocellular Carcinoma; Ovarian Cancer; Colorectal Cancer; Non-Small Cell Lung Cancer

Treatments: Drug: Pembrolizumab; Drug: Nanrilkefusp Alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT05256381

2021-005774-25 (EudraCT Number)

AURELIO-04 (Other Identifier)

SC104

MK-3475-D13 (Other Identifier)

KEYNOTE-D13 (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 166 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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166 participants in 1 patient group

Nanrilkefusp Alfa and Pembrolizumab

Experimental group

Description:

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.

Treatment:

Drug: Nanrilkefusp Alfa

Drug: Pembrolizumab