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

NCT05492682 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: VALO-0012021-002529-13
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From study protocol day 1 (baseline) until 1 month

• 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.

  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.

  From first month through study completion, an average of 4.5 months.

Secondary Outcomes (6)

• 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.

  Change from Baseline through study completion, an average of 5 months.

• Measurement of NY-ESO-1 and MAGE A3 antibodies in serum.

  Change from Baseline to an average of 3,5 months

• To determine the number of tumor infiltrating lymphocytes (TILs) in tumor mass.

  Change from Baseline to an average of 3 months

• To determine objective response rate (ORR).

  Change from Baseline through study completion, an average of 5 months.

• To determine overall survival.

  Change from Baseline through study completion, an average of 5 months.

Other Outcomes (4)

• Measurement of PFS according to RECIST 1.1, itRECIST, and PERCIST 1.0.

  Change from Baseline through study completion, an average of 5 months.

• 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).

  Changes from baseline to an average of 3,5 months.

• Immune phenotyping in tumor mass.

  Changes from baseline to to an average of 3 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

Patients in Cohort 1 are treated with PeptiCRAd-1 administered i.t.

Drug: PeptiCRAd-1; Drug: Cyclophosphamide; Drug: Pembrolizumab

Cohort 2

EXPERIMENTAL

Patients in Cohort 2 are treated with PeptiCRAd-1 administered i.t. and s.c.

Drug: PeptiCRAd-1; Drug: Cyclophosphamide; Drug: Pembrolizumab

Interventions

PeptiCRAd-1 DRUG

All patients will receive PeptiCRAd-1.

Cohort 1; Cohort 2

Cyclophosphamide DRUG

All patients will be pre-treated with one single dose of Cyclophosphamide.

Cohort 1; Cohort 2

Pembrolizumab DRUG

All patients will receive 6 doses of Pembrolizumab within the study.

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Male or female, ≥18 years of age.
• 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 osteosarcoma
• Inoperable and/or advanced colorectal cancer, patients assessed as positive for NY-ESO-1 or MAGE-A3 expression at baseline
• Inoperable and/or advanced/metastatic sarcoma, patients assessed as positive for NY-ESO-1 or MAGE-A3 expression at baseline
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Tumor lesion which is deemed feasible for biopsy and injection
• ECOG/WHO performance status 0 to 1.
• 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

You may not qualify if:

• Receipt of any oncolytic virus treatment, or administration of a vaccine containing live virus within 4 weeks before Day 1.
• 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.
• Prior or concomitant radiotherapy within 4 weeks before Day 1.
• Participation in a study with an investigational drug or device within 4 weeks prior to Day 1.
• Active bacterial, viral, or fungal infection that requires systemic therapy.
• Active autoimmune disease that has required systemic treatment in the past two years.
• 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.
• 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.
• Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C or active tuberculosis.
• 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.
• 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

Sponsors & Collaborators

• Valo Therapeutics Oy: lead

Study Sites (3)

Krankenhaus Nordwest

Frankfurt, Germany

Location

National Center for Tumor Diseases

Heidelberg, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

MeSH Terms

Conditions

Melanoma; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Sarcoma, Synovial; Liposarcoma, Myxoid; Colorectal Neoplasms; Osteosarcoma; Sarcoma

Interventions

Cyclophosphamide; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Liposarcoma; Neoplasms, Adipose Tissue; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2022
• First Posted: August 8, 2022
• Study Start: February 2, 2023
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 5, 2025

Record last verified: 2025-08

Locations

DE (3)