LUMINOS-103: A Basket Trial of Safety & Efficacy of Lerapolturev With or Without Checkpoint Inhibitors

NCT04690699 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: LUMINOS-103
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1/2, open-label, multi-center, single arm basket study evaluating the administration of lerapolturev ± anti programmed cell death protein 1 (PD 1)/programmed death-ligand 1 (PD L1) monoclonal antibody (mAb) (which will be referred to throughout this protocol as "anti-PD-1/L1 therapy") therapy in adult patients with solid tumor cancers. Non-muscle invasive Bladder Cancer has been selected as the tumor specific cancer of interest for enrollment.

Conditions

Solid Tumor; Bladder Cancer; Non-muscle-invasive Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Underwent TURBT or Cystectomy as Scheduled

  To evaluate the safety and tolerability of lerapolturev monotherapy administered by intravesical instillation to patients with recurrent NMIBC intended for TURBT or cystectomy

  1 month

Study Arms (2)

Cohort E: Lerapolturev

EXPERIMENTAL

Subjects will be treated with lerapolturev by intravesical instillation

Biological: Lerapolturev

Cohort F: Lerapolturev + 5% DDM

EXPERIMENTAL

Subjects will be treated with lerapolturev by intravesical instillation after a sequence of 5% DDM and saline washes

Biological: Lerapolturev; Other: 5% DDM

Interventions

Lerapolturev BIOLOGICAL

Lerapolturev administered via intravesical instillation once

Cohort E: Lerapolturev; Cohort F: Lerapolturev + 5% DDM

5% DDM OTHER

5% DDM and saline washes

Cohort F: Lerapolturev + 5% DDM

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Age ≥ 18 years of age at the time of signing the informed consent.
• Prior CDC-recommended vaccination series against PV and has received a boost immunization with trivalent Poliovirus Vaccine Inactivated (IPOL®) (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to Cycle 1 Day 1.
• \* Note: Patients who are unsure of their vaccination status must provide evidence of anti-PV immunity prior to enrollment, as applicable.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh biopsy) with an associated pathology report documenting the histology of the tumor type of interest must be confirmed to be available to send to the Sponsor.
• \* Note: additional details can be found in the tumor specific appendix.
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
• Adequate bone marrow and liver function as assessed by the following:
• Hemoglobin ≥9.0 g/dl (patients may be transfused)
• Lymphocyte count ≥ 0.5 x 109/L (500/µL)
• Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/µL)
• Platelet count ≥100 x 109/L (100,000/µL) without transfusion
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Subjects with documented liver metastases: AST and ALT ≤5 x ULN

You may not qualify if:

• Any radiotherapy, chemotherapy, immunotherapy, biological, investigational, or hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast cancer or prostate cancer defined as M0 disease or prostate-specific antigen persistence/recurrence without metastatic disease) within 21 days of Cycle 1 Day 1.
• Patients requiring anticoagulation with warfarin are excluded. Additional eligibility criteria for anticoagulation requirements for each solid tumor cancer of interest will be provided in the tumor specific appendix.
• Presence of central nervous system (CNS) metastases requiring immediate treatment with radiation therapy or steroids (ie, patient must be off steroids administered for brain metastases for ≥ 14 days prior to Cycle Day 1). Leptomeningeal disease is excluded regardless of clinical stability or treatment status.
• Clinically significant (ie, active) cardiovascular disease at the time of signing the informed consent; for example, cerebrovascular accidents (≤ 6 months before the first dose of lerapolturev, myocardial infarction (≤ 6 months before the first dose of lerapolturev), unstable angina, serious cardiac arrythmia requiring medication, or uncontrolled symptomatic congestive heart failure \[Class II or higher as defined by the New York Heart Association \[NYHA\] functional classification system; see Appendix 4\]).
• QTcF interval \> 450 msec (males) or \> 470 msec (females) at Screening (confirmed in triplicate). For patients with ventricular pacemakers or bundle branch block, QTcF \>500 msec.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Cycle Day 1, or anticipation of the need for major surgical procedure during the course of the study.
• Active or history of autoimmune disease or immune deficiency within previous 2 years, with the following exceptions:
• History of autoimmune-related hypothyroidism that is managed by thyroid replacement hormone
• Type 1 diabetes mellitus that is well-controlled (as determined by the Investigator) by an established insulin regimen
• Eczema, psoriasis, or lichen simplex chronicus with dermatologic manifestations only (eg, patients with psoriatic arthritis are excluded), provided all of the following conditions are met:
• Rash must cover \< 10% of body surface area
• Disease is well-controlled (as determined by the Investigator) at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within 12 months of Cycle 1 Day 1
• History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• History of radiation pneumonitis in the radiation field (fibrosis) is allowed.

Sponsors & Collaborators

• Istari Oncology, Inc.: lead

Study Sites (1)

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

DDMS

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Istari Oncology

info@istarioncology.com

919-245-7662

Study Officials

• Lisa Franklin

  Istari Oncology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: December 31, 2020
• Study Start: August 1, 2021
• Primary Completion: April 4, 2024
• Study Completion: June 12, 2024
• Last Updated: October 24, 2024
• Results First Posted: October 24, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)