START: Safety and Anti-Tumor Activity of PeptiCRAd-1 in Treatment of Cancer

• ClinicalTrials.gov Identifier: NCT05492682
• Recruitment Status: Recruiting
• First Posted: August 8, 2022
• Last Update Posted: January 12, 2024
• Sponsor: Valo Therapeutics Oy
• Information provided by (Responsible Party): Valo Therapeutics Oy

Tracking Information

• First Submitted Date: May 18, 2022
• First Posted Date: August 8, 2022
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: February 2, 2023
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2023)

• Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 monotherapy. [ Time Frame: From study protocol day 1 (baseline) until 1 month ]
  The incidence and characteristics of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 monotherapy in order to evaluate the safety and tolerability.
• Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 and CPI combination. [ Time Frame: From first month through study completion, an average of 4.5 months. ]
  The incidence and characteristics of TEAEs, SAEs and DLTs will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 and CPI combination in order to evaluate the safety and tolerability.

Original Primary Outcome Measures (submitted: August 5, 2022)

• Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 monotherapy. [ Time Frame: From study protocol day 1 (baseline) until day 22. ]
  The incidence and characteristics of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 monotherapy in order to evaluate the safety and tolerability.
• Measurement of Safety and tolerability indexes (Incidence of TEAEs, SAEs and DLTs as assessed by CTCAE version 5.0 and changes in assessed safety parameters) for PeptiCRAd-1 and CPI combination. [ Time Frame: From day 22 through study completion, an average of 4.5 months. ]
  The incidence and characteristics of TEAEs, SAEs and DLTs will be assessed by CTCAE version 5.0 and changes from baseline in assessed safety parameters (Hematology tests, Clinical Chemistry safety tests, urine analysis ECOG/WHO performance status, vital signs) are measured in patients receiving PeptiCRAd-1 and CPI combination in order to evaluate the safety and tolerability.

Current Secondary Outcome Measures (submitted: February 1, 2023)

• Measurement of New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) and Melanoma-associated antigen 3 (MAGE A3) specific T-cells in peripheral blood. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Presence vs. no presence of cellular immune response.
• Measurement of NY-ESO-1 and MAGE A3 antibodies in serum. [ Time Frame: Change from Baseline to an average of 3,5 months ]
  Presence vs. no presence of humoral response.
• To determine the number of tumor infiltrating lymphocytes (TILs) in tumor mass. [ Time Frame: Change from Baseline to an average of 3 months ]
  Number of TILs in tumor biopsies.
• To determine objective response rate (ORR). [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Objective responses according to RECIST 1.1, iRECIST, itRECIST and PERCIST 1.0.
• To determine overall survival. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Overall survival presented in Kaplan-Meier plot.
• Correlation between immune activation in peripheral blood and tumor mass and clinical outcome. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Correlation between immune activation (immunological variables) in peripheral blood and tumor mass and clinical outcome (ORR, OS).

Original Secondary Outcome Measures (submitted: August 5, 2022)

• Measurement of New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) and Melanoma-associated antigen 3 (MAGE A3) specific T-cells in peripheral blood. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Presence vs. no presence of cellular immune response.
• Measurement of NY-ESO-1 and MAGE A3 in serum. [ Time Frame: Change from Baseline to Day 106. ]
  Presence vs. no presence of humoral response.
• To determine the number of tumor infiltrating lymphocytes (TILs) in tumor mass. [ Time Frame: Change from Baseline to Day 85. ]
  Number of TILs in tumor biopsies of injected and non-injected tumors.
• To determine objective response rate (ORR). [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Objective responses according to RECIST 1.1, iRECIST, itRECIST and PERCIST 1.0.
• To determine overall survival. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Overall survival presented in Kaplan-Meier plot.
• Correlation between immune activation in peripheral blood and tumor mass and clinical outcome. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Correlation between immune activation (immunological variables) in peripheral blood and tumor mass and clinical outcome (ORR, OS).

Current Other Pre-specified Outcome Measures (submitted: February 1, 2023)

• Measurement of PFS according to RECIST 1.1, itRECIST, and PERCIST 1.0. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Progression free survival (PFS) is measured, according to RECIST 1.1, iRECIST, itRECIST, and PERCIST 1.0, and will be presented using the Kaplan-Meier approach.
• Measurement of virus shedding profiles (presence of infective virus and virus DNA in blood, urine, buccal, fecal and injection site swabs by infectivity assay and qPCR). [ Time Frame: Changes from baseline to an average of 3,5 months. ]
  Presence of infective virus (infectivity assay) and virus DNA (quantitative polymerase chain reaction, qPCR) will be measured in blood, urine, buccal, fecal and injection site swabs.
• Immune phenotyping in tumor mass. [ Time Frame: Changes from baseline to to an average of 3 months ]
  Measurement of biological and immunological changes (including number of T-cells) in biopsies of injected and non-injected tumors over time.
• Measurement of the phenotype of circulating immune cells in peripheral blood. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  The immunological landscape in peripheral blood will be determined.

Original Other Pre-specified Outcome Measures (submitted: August 5, 2022)

• Measurement of PFS according to RECIST 1.1, itRECIST, and PERCIST 1.0. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  Progression free survival (PFS) is measured, according to RECIST 1.1, iRECIST, itRECIST, and PERCIST 1.0, and will be presented using the Kaplan-Meier approach.
• Measurement of virus shedding profiles (presence of infective virus and virus DNA in blood, urine, buccal, fecal and injection site swabs by infectivity assay and qPCR). [ Time Frame: Changes from baseline to Day 106. ]
  Presence of infective virus (infectivity assay) and virus DNA (quantitative polymerase chain reaction, qPCR) will be measured in blood, urine, buccal, fecal and injection site swabs.
• Immune phenotyping in tumor mass. [ Time Frame: Changes from baseline to Day 85. ]
  Measurement of biological and immunological changes (including number of T-cells) in biopsies of injected and non-injected tumors over time.
• Measurement of the phenotype of circulating immune cells in peripheral blood. [ Time Frame: Change from Baseline through study completion, an average of 5 months. ]
  The immunological landscape in peripheral blood will be determined.
• Measurement of expression levels of target antigens in tumors. [ Time Frame: Changes form baseline to Day 85. ]
  Expression levels of target antigens in tumors are measured to identify potential biomarkers.
• Measurement of PDL1 expression in tumor cells. [ Time Frame: Changes form baseline to Day 85. ]
  Expression of PDL1 in tumor cells is measured.
• Mutational load in tumor mass. [ Time Frame: Changes form baseline to Day 85. ]
  To identify potential biomarkers.

Descriptive Information

• Brief Title: START: Safety and Anti-Tumor Activity of PeptiCRAd-1 in Treatment of Cancer
• Official Title: A Study to Evaluate the Safety and Immune Activity of PeptiCRAd-1 in Combination With Pembrolizumab in Patients With Injectable Solid Tumors in Indications Known to Express NY-ESO-1 and MAGE-A3
• Brief Summary: This study is being conducted to explore the immunological mechanism of action of Peptide-coated Conditionally Replicating Adenovirus-1 (PeptiCRAd-1) plus Checkpoint inhibitor (CPI) therapy in multiple cancer types, as well as to obtain early information on the safety of this combination therapy.
• Detailed Description: This is a Phase I, open-label, non-randomized, first-in-human study. All patients will be pre-treated with a low dose of intravenous (i.v.) Cyclophosphamide (CPO) followed by monotherapy doses of PeptiCRAd-1. Patients will receive a total of 6 doses of PeptiCRAd-1 during the study. PeptiCRAd-1 will be administered by intratumoral (i.t.) injection with priming doses administered on Days 1, 4, and 8, and the first booster dose on Day 15, followed by combination therapy with PeptiCRAd-1 and i.v. CPI (pembrolizumab).
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Melanoma (Skin)
• Triple-Negative Breast Cancer
• Non-Small Cell Lung Cancer
• Synovial Sarcoma
• Myxoid Liposarcoma
• Colorectal Cancer

Intervention

• Drug: PeptiCRAd-1
  All patients will receive 6 doses of PeptiCRAd-1.
• Drug: Cyclophosphamide
  All patients will be pre-treated with one single dose of Cyclophosphamide.
• Drug: Pembrolizumab
  All patients will receive 6 doses of Pembrolizumab within the study.

Study Arms

Experimental: open label non-randomized

All patients will follow the same treatment schedule.

Interventions:

• Drug: PeptiCRAd-1
• Drug: Cyclophosphamide
• Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 5, 2022): 15
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Written informed consent.
2. Male or female, ≥18 years of age.

3. Patients with any 1 of the following histologically confirmed tumors and who qualifies for new or continued CPI therapy and relapsing to/after standard therapy or the patient has refused or does not tolerate standard therapy:

   • Inoperable/metastatic cutaneous malignant melanoma
   • Relapsed or newly diagnosed locally advanced inoperable/metastatic TNBC
   • Inoperable advanced/metastatic non-squamous NSCLC
   • Inoperable and/or advanced Synovial or myxoid round cell sarcoma
   • Inoperable and/or advanced colorectal cancer, patients assessed as positive for NY-ESO-1 or MAGE-A3 expression at baseline
4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
5. Tumor lesion which is deemed feasible for biopsy and injection
6. ECOG/WHO performance status 0 to 1.

7. Acceptable liver and renal function, defined as:

   • Total bilirubin ≤1.5 x upper limit of normal (ULN; does not include patients with Gilbert's Disease), and
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN, and
   • Serum creatinine ≤1.5 x ULN

8. Acceptable hematological function, defined as:

   • Hemoglobin ≥10 g/dL, and
   • Neutrophils ≥1.5 x 109/L, and
   • Platelet count ≥100 x 109/L Patients may be transfused to meet the hemoglobin entry criteria.
9. Acceptable coagulation status defined by international normalized ratio (INR) of blood clotting, prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit of normal.

10. Negative pregnancy test at screening in all women of childbearing potential (WOCBP). Such patients must agree to use a highly effective method of contraception (Appendix 1) during study intervention and for 3 months after the last virus treatment, 4 months after the last dose of pembrolizumab, and 12 months after CPO dosing. Male patients and male partners of female patients must also use barrier contraception, i.e., condom, for the time periods specified for WOCBP, plus a further 3 month period.

    Urine pregnancy tests should have a sensitivity of at least 25 mIU/mL for human chorionic gonadotropin (hCG). If the urine test is positive, it must be followed by a quantitative analysis of hCG concentration in blood.

11. Prior therapy with an immune CPI is allowed provided a 6-week washout period is observed for patients with prior programmed cell death (PD)1 or PDL1 treatment

Exclusion Criteria:

1. Receipt of any oncolytic virus treatment, or administration of a vaccine containing live virus within 4 weeks before Day 1.
2. Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1. Inhaled or topical corticosteroid use is allowed.
3. Prior or concomitant radiotherapy within 4 weeks before Day 1.
4. Participation in a study with an investigational drug or device within 4 weeks prior to Day 1.
5. Active bacterial, viral, or fungal infection that requires systemic therapy.
6. Active autoimmune disease that has required systemic treatment in the past two years.
7. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient, if included in this study.
8. Any concomitant medical condition requiring receipt of a therapeutic anticoagulant that, in the opinion of the treating physician, cannot safely be withheld to allow for repeated injection of PeptiCRAd 1 and tumor biopsies.
9. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C or active tuberculosis.

10. Known active central nervous system metastases. Patients with leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiographic signs of CNS hemorrhage are excluded.

    Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted.

11. Any prior severe AE according to Common Terminology Criteria for Adverse Events (CTCAE), severe hypersensitivity reaction attributed to prior anti-PD1 or PDL1 therapy or components of the study intervention or has a history of any contraindication that, in the investigator's opinion, would contraindicate pembrolizumab administration such as:

    • Resolution of side effect of prior anti-PD1 or PDL1 therapy to Grade 1
    • Grade 2 or higher pneumonitis
    • Grade 4 AST or ALT elevation
    • Grade 3 or higher colitis attributable to immunotherapy Note: in the absence of clinical symptoms of pancreatitis, elevations of amylase or lipase are not contraindications to therapy on this trial.
12. History of or planned tissue / organ transplant.
13. Females who are pregnant or breast feeding or expecting to conceive within the projected duration of the study starting with the screening visit or males expecting to father children within the projected duration of the study starting with the screening visit.
14. Unwillingness or inability to comply with the study protocol for any reason.
15. Admission to an institution by virtue of an order issued by the judicial or administrative authorities.
16. Sponsor or Contract Research Organization employees, or employees under the direct supervision of the investigator or the investigational sites and/or involved directly in the study.
17. Prior or concurrent malignancy, unless the natural history or treatment of the disease does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Backman, MsC; 0505876088 ext 358; info@valotx.com

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT05492682
• Other Study ID Numbers: VALO-001; 2021-002529-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Valo Therapeutics Oy
• Original Responsible Party: Same as current
• Current Study Sponsor: Valo Therapeutics Oy
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Valo Therapeutics Oy
• Verification Date: January 2024