Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Subjects will be treated with lerapolturev by intravesical instillation

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

Lerapolturev administered via intravesical instillation once

Lerapolturev

5% DDM

Lisa Franklin

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.

Patients with recurrent non-muscle invasive bladder cancer (NMIBC) intended for transurethral resection of bladder tumor (TURBT) or cystectomy will receive lerapolturev by intravesical instillation. Approximately 12-15 patients will be enrolled.

LUMINOS-103: A Basket Trial Evaluating the Safety and Efficacy of Lerapolturev (PVSRIPO) and Lerapolturev in Combination With Anti-PD-1/L1 Checkpoint Inhibitors in Patients With Advanced Solid Tumors

Istari Oncology, Inc.

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Lerapolturev (up to 1.6x10\^9 TCID50) administered via direct injection of up to 6 lesions given weekly for 7 weeks, followed by every 3 weeks thereafter.

Lerapolturev (up to 1.6x10\^9 TCID50) administered via direct injection of up to 6 lesions given weekly for 7 weeks, followed by every 3 or 4 weeks thereafter. Anti-PD-1 therapy given as per the anti-PD-1 approved package insert.

Lerapolturev administered via direct lesion injection

Anti-PD-1 Checkpoint Inhibitor administered per package insert instructions

Anti-PD-1 Checkpoint Inhibitor

A Phase 2 study to investigate the efficacy and safety of lerapolturev alone or in combination with a programmed death receptor-1 (anti-PD-1) inhibitor.

This multi-center, open-label, randomized, Phase 2 will investigate the efficacy and safety of lerapolturev alone (Arm 1) or in combination with an anti-PD-1 inhibitor (Arm 2). Following a 6 participant safety run-in period, up to approximately 50 participants with cutaneous melanoma who previously failed anti-PD-1/L1-based therapy will be randomized 1:1 to receive either lerapolturev or lerapolturev plus an anti-PD-1.

LUMINOS-102: Lerapolturev With or Without Immune Checkpoint Blockade in Advanced PD-1 Refractory Melanoma

Lerapolturev (Formerly Known as PVSRIPO) With or Without Immune Checkpoint Blockade in Advanced PD-1 Refractory Melanoma

* Assessment and identification of genetic, cytologic, histologic and/or other markers in tumor biopsies and PBMC samples that may correlate with response.
* Assessment of changes over time in immune markers, including, but not limited to immune cell density, T cell receptor repertoire, and chemokine and/or cytokine profile in blood, samples, and/or tissue

ORR in the following subgroups:

* Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020)
* BRAF wild type and mutant
* LDH levels at baseline
* Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks)
* Crossover to combination arm from lerapolturev monotherapy

DOR in the following subgroups:

* Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020)
* BRAF wild type and mutant
* LDH levels at baseline
* Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks)
* Crossover to combination arm from lerapolturev monotherapy

DRR in the following subgroups:

* Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020)
* BRAF wild type and mutant
* LDH levels at baseline
* Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks)
* Crossover to combination arm from lerapolturev monotherapy

DCR in the following subgroups:

* Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020)
* BRAF wild type and mutant
* LDH levels at baseline
* Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks)
* Crossover to combination arm from lerapolturev monotherapy

DCR-6mo in the following subgroups:

* Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020)
* BRAF wild type and mutant
* LDH levels at baseline
* Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks)
* Crossover to combination arm from lerapolturev monotherapy

OS in the following subgroups:

* According to treatment arm and AJCC stage at baseline
* Primary versus acquired resistance as defined by Kluger et al
* BRAF wild type and mutant
* LDH levels at baseline
* Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks)
* Crossover to combination arm from lerapolturev monotherapy

PFS in the following subgroups:

* According to treatment arm and AJCC stage at baseline
* Primary versus acquired resistance as defined by Kluger et al
* BRAF wild type and mutant
* LDH levels at baseline
* Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks)
* Crossover to combination arm from lerapolturev monotherapy

The proportion of patients achieving confirmed complete (CR) or partial response (PR), per RECIST 1.1 criteria

The frequency and severity of treatment-emergent adverse events (TEAE) via Common Terminology Criteria for Adverse Events (CTCAE, v5.0)

Lerapolturev AESIs and anti-PD-1 immune related AEs (irAEs)

Study treatment discontinuation due to AEs

Changes from baseline in the number of CD8+ tumor infiltrating lymphocytes (TILs)

Changes from baseline in PD-L1 expression

Overall survival (OS): time from treatment group assignment until death from any cause.

Duration of Response (DOR): time from confirmed objective response (CR or PR per RECIST 1.1) until unequivocal disease progression or death, whichever occurs first

Disease control rate (DCR): the proportion of patients achieving confirmed CR, confirmed PR, or stable disease (SD) per RECIST1.1, as best response.

Disease control rate-6months (DCR-6mo): the proportion of patients achieving confirmed CR (any duration), confirmed PR (any duration) or SD (≥ 6 months) per RECIST 1.1 as best response.

Durable Response Rate (DRR): the proportion of participants with confirmed CR or PR (per RECIST 1.1) lasting at least 6 months

Progression-free survival (PFS): time (number of months) from treatment group assignment until date of documented radiologic disease progression per RECIST 1.1 or death due to any cause, whichever comes first

Symptoms and General Pathology

Recurrence

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Antineoplastic Agents

All Drugs and Chemicals

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Lerapolturev (intratumoral) will be dosed by Convection Enhanced Delivery (CED), infused twice, 4 days apart, in the remaining disease of recurrent Glioblastoma (rGBM) subjects following maximal safe resection of the disease recurrence.

To assess treatment response and/or immunologic responses in the brain, a tissue biopsy of the area infused will be recommended 5 weeks (± 1 week) after the 2nd lerapolturev infusion via CED, in the event that changes suggestive of tumor progression are seen on the MRI obtained 4-5 weeks after the 2nd lerapolturev infusion via CED.

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Lerapolturev (intratumoral) will be given by Convection Enhanced Delivery (CED), infused twice, 4 days apart, in the remaining disease of recurrent Glioblastoma (rGBM) subjects following maximal safe resection of their disease recurrence. This will be followed by subcutaneous injections of lerapolturev in the cervical perilymphatic (CPL) area on the same side as their tumor, weekly for 4 weeks and afterward every 3 weeks for about a year.

Following maximal safe resection of their tumor recurrence subjects will receive Lomustine as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.

Lerapolturev (intratumoral) will be dosed at 2x108 TCID50 in 3.0 mL x 2 doses (total dose 4x108 TCID50) by Convection Enhanced Delivery.

For the patients randomized to the lerapolturev Arm 1 of Stage 2, seven days (±2 days) following completion of the 2nd intratumoral infusion of lerapolturev, patients will begin cervical perilymphatic subcutaneous injection of lerapolturev at a dose of 2 x 108 TCID50 (in 0.5 ml diluent) around the cervical lymph node chain ipsilateral to the intracranial tumor.

Lomustine will be given as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.

Lomustine Pill

Madison Shoaf, MD

Stevie Threatt

The purpose of this research study is to determine the safety and efficacy of administering two doses of lerapolturev in residual disease (within tumor margins) after surgery, followed later by repeated injections of lerapolturev in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adult patients diagnosed with recurrent glioblastoma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

The study will be conducted in two stages: Approximately twelve patients with recurrent supratentorial glioblastoma will enroll in stage 1.

Stage 1 is a safety lead-in which will assess the safety of lerapolturev when infused twice, 4 days apart, via Convection Enhanced Delivery (CED) in the residual disease of recurrent Glioblastoma (GBM) patients following maximal safe resection of the enhancing/necrotic portion of the disease recurrence.

A tissue biopsy of the area infused will be recommended 5 weeks (± 1 week) after the 2nd lerapolturev infusion via CED, if imaging changes suggest tumor progression vs. immune effect on the MRI obtained 4-5 weeks after the 2nd lerapolturev infusion via CED.

Stage 2 is a Phase 2 randomized clinical trial to compare the efficacy and safety of two treatment regimens for recurrent GBM patients who undergo maximal safe resection for their recurrence. Approximately eighty patients with recurrent supratentorial glioblastoma will enroll in stage 2 of the study.

Stage 2 has 2 arms and is randomized, like the flip of a coin. Arm 1 is Lerapolturev and Arm 2 is Lomustine. After the recurrent tumor has been removed by surgery, subjects will be randomly assigned to receive either the FDA-approved chemotherapy (lomustine) or the study drug (lerapolturev). Subjects receive lerapolturev infused in the residual disease via CED twice, 4-day apart. About 1 week after the 2nd lerapolturev infusion, subjects will start subcutaneous (under the skin) injections of lerapolturev into the area of the cervical lymph nodes (head and neck) nearest to their tumor weekly for 4 weeks and afterward every 3 weeks for about a year.

Subjects assigned to receive lomustine will begin taking it 3-4 weeks after surgery to remove their recurrent tumor. One prescribed dose of lomustine will be taken no more than once every 6 weeks, for no more than 1 year or up to 9 cycles.

Subjects will be followed for serious adverse events (side effects) for 30 days after stopping the study. Subjects' medical records will be reviewed for the remainder of their life, in order to collect data on subsequent treatments, disease progression, tumor size/volume, and survival.

There are risks to the study drug, lerapolturev, and the chemotherapy drug, lomustine. The most common risks of lerapolturev are headache, seizure, weakness on one side of the body, difficulty thinking or processing, difficulty receiving or responding to sensory information, fatigue, and difficulty speaking or comprehending. Risks associated with infusion procedure include mild discomfort at the infusion site, bleeding in the brain, pain, infection, and swelling of the brain. The study drug and procedures used together could also potentially cause more serious side effects. The most common risks of lomustine are changes in your red blood cell count, changes in platelets, changes in your liver, feeling confused and tired, poor appetite, and loss of ability to conceive or father a child.

Lerapolturev (PVSRIPO) in GBM

Randomized Phase 2 Clinical Trial of Repeated Intratumoral and Cervical Perilymphatic Lerapolturev Injections Versus Lomustine in Recurrent Glioblastoma (GBM)

Dose-limiting toxicities (DLTs) are defined as any of the following events that are possibly, probably, or definitely attributable to study treatment (i.e., lerapolturev) during dose escalation (Stage 1):

* Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms
* Any life-threatening event within 2 weeks
* Treatment-related death at least possibly, probably, or definitely attributable to study treatment
* Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion

Unacceptable toxicity is defined as any of the following events that are possibly, probably, or definitely attributable to study treatment:

* Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms
* Any life-threatening event within 2 weeks
* Treatment-related death at least possibly, probably, or definitely attributable to study treatment
* Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion

Median OS, where OS is defined as the time between randomization and death

Median PFS, where PFS is defined as the time between randomization and initial failure (disease progression or death)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LUMINOS-103: A Basket Trial Evaluating the Safety and Efficacy of Lerapolturev (PVSRIPO) and Lerapolturev in Combination With Anti-PD-1/L1 Checkpoint Inhibitors in Patients With Advanced Solid Tumors	NCT04690699	Solid Tumor Bladder Cancer Non-muscle-inva...	Lerapolturev 5% DDM	18 Years -	Istari Oncology, Inc.
LUMINOS-102: Lerapolturev With or Without Immune Checkpoint Blockade in Advanced PD-1 Refractory Melanoma	NCT04577807	Melanoma	Lerapolturev Anti-PD-1 Check...	18 Years -	Istari Oncology, Inc.
Lerapolturev (PVSRIPO) in GBM	NCT06177964	Recurrent Supra...	Lerapolturev Lomustine Pill	18 Years -	Duke University

Spots Global Cancer Trial Database for lerapolturev

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We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.