PVSRIPO for Patients With Unresectable Melanoma

NCT03712358 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: Pro00090774K08CA237726
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase I study of oncolytic polio/rhinovirus recombinant (PVSRIPO) to primarily characterize the safety and tolerability of PVSRIPO in patients with AJCC Stage IIIB, IIIC, or IV melanoma in a modified 3+3 phase 1 trial design. Lesion biopsies and blood samples will be obtained pre- and post-injection throughout the study for routine histology/molecular genetic testing and immunologic analysis, respectively. Exploratory objectives include describing the response rates of PVSRIPO-injected versus non-injected lesion(s), the number of CD8 positive T cells present in the tumor biopsies before and after injection of PVSRIPO, and after PVSRIPO administration: the pathologic response in tumor biopsies, changes in the tumor microenvironment, and how systemic immune cell populations may change.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Dose Limiting Toxicity by Cohort

  To characterize the safety and tolerability of PVSRIPO in American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC, or IV melanoma.

  24 months

Other Outcomes (6)

• Response Rates Via Measurement of Cutaneous Lesions Every 3 Weeks

  24 months

• Number of CD8 Positive T Cells by Immunohistochemistry on Pre Treatment and Post Treatment Biopsy (Cohorts 0-3 Only)

  4.1 months

• The Change in Tumor Pathology From Baseline to After PVSRIPO Injection

  4.1 months

Study Arms (5)

Cohort 0 (PVSRIPO)

EXPERIMENTAL

A single dose of PVSRIPO into a single lesion.

Biological: PVSRIPO

Cohort 1 (PVSRIPO)

EXPERIMENTAL

A single dose of PVSRIPO into 2 different lesions, 21 days apart, when applicable per dose escalation guidelines.

Biological: PVSRIPO

Cohort 2 (PVSRIPO)

EXPERIMENTAL

A single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines.

Biological: PVSRIPO

Cohort 3 (PVSRIPO)

EXPERIMENTAL

A single dose of PVSRIPO into 3 different lesions, 21 days apart, when applicable per dose escalation guidelines.

Biological: PVSRIPO

Cohort 4 (PVSRIPO)

EXPERIMENTAL

A single dose of PVSRIPO into a single lesion, followed by PVSRIPO injected into up to 6 lesions at Day 10 and every 21 days thereafter.

Biological: PVSRIPO

Interventions

PVSRIPO BIOLOGICAL

Intralesional injection of PVSRIPO.

Cohort 0 (PVSRIPO); Cohort 1 (PVSRIPO); Cohort 2 (PVSRIPO); Cohort 3 (PVSRIPO); Cohort 4 (PVSRIPO)

Eligibility Criteria

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

You may qualify if:

• Undergone prior vaccination against PV and received a boost immunization with trivalent IPOL® (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to administration of PVSRIPO (within 6 months of PVSRIPO retreatment).
• a. Note: Patients who are unsure of their prior vaccination status/who have not been vaccinated must provide proof of vaccination and/or evidence of anti-PV immunity prior to enrollment, as applicable.
• The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week prior to administration of the study agent.
• Patient must have histologically proven unresectable, recurrent, melanoma, stage IIIB, IIIC, or stage IV (AJCC staging must be documented in patient's medical record, as determined by CT of the chest, abdomen and pelvis, and/or whole body positron emission tomography (PET) scan, and MRI of the brain within 4 weeks prior to administration of study drug).
• Patients with BRAF mutations, must have failed at least 2 lines of therapy, specifically one BRAF targeted therapy and at least one anti-PD-1 based therapy. For BRAF wild type, patients must have failed at least one anti-PD-1 based therapy.
• Patient must be ≥ 18 years of age.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) / Zubrod status of 0-1.
• Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the immune-related response criteria (irRC).
• At least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion ≥ 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of ≥ 10 mm (Cohorts 0 and possibly 1). For cohorts where 2 or 3 injections are planned (Cohorts 1 and 2), the patient must have at least 2 injectable melanoma lesions (when 2 doses are planned) or ≥3 injectable melanoma lesions when at least 3 doses are planned in different lesions (Cohorts 2 through 4).
• a. Note: PVSRIPO retreatment requires ≥2 lesions amenable to injection.
• At least one measurable lesion that will not be injected.
• Serum lactate dehydrogenase (LDH) levels less than 1.5 x upper limit of normal (ULN).
• Patient must have adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin \> 9.0 g/dl
• White blood count (WBC) of \> 2000 m3

You may not qualify if:

• Females who are pregnant or breast-feeding.
• Adults of reproductive potential not employing an effective method of birth control.
• Patients with severe, active co-morbidity, defined as follows:
• Patients with an active infection requiring treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C).
• Patients with impaired cardiac function or clinically significant cardiac disease, such as congestive heart failure requiring treatment (New York Heart Association Class ≥ 2), uncontrolled hypertension or clinically significant arrhythmia; QTcF \> 470 msec on ECG if performed or congenital long QT syndrome; acute myocardial infarction or unstable angina pectoris \< 3 months prior to study.
• Patients with known lung (FEV1 \< 50%) disease or uncontrolled diabetes mellitus (HgbA1c\>7).
• Patients with albumin allergy.
• Known immunosuppressive disease, human immunodeficiency virus (HIV) infection, or chronic Hepatitis B or C.
• Patients with a previous history of neurological complications due to PV infection.
• Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used. Toxicities must have resolved to CTCAE grade 1 or less with the following exceptions (alopecia, fatigue, vitiligo).
• Patients with undetectable anti-tetanus toxoid IgG.
• Patients with known history of agammaglobulinemia.
• Patients on greater than 10 mg per day of prednisone within the 2 weeks prior to admission for PVSRIPO injection.
• Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups).
• Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Istari Oncology, Inc.: lead
• Duke University: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (3)

• Brown MC, Beasley GM, McKay ZP, Yang Y, Desjardins A, Randazzo DM, Landi D, Ashley DM, Bigner DD, Nair SK, Gromeier M. Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils. J Immunother Cancer. 2023 Apr;11(4):e006463. doi: 10.1136/jitc-2022-006463.

  PMID: 37072349 DERIVED

• Beasley GM, Brown MC, Farrow NE, Landa K, Al-Rohil RN, Selim MA, Therien AD, Jung SH, Gao J, Boczkowski D, Holl EK, Salama AKS, Bigner DD, Gromeier M, Nair SK. Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma. J Immunother Cancer. 2022 Sep;10(9):e005052. doi: 10.1136/jitc-2022-005052.

  PMID: 36175036 DERIVED

• Beasley GM, Nair SK, Farrow NE, Landa K, Selim MA, Wiggs CA, Jung SH, Bigner DD, True Kelly A, Gromeier M, Salama AK. Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma. J Immunother Cancer. 2021 Apr;9(4):e002203. doi: 10.1136/jitc-2020-002203.

  PMID: 33875611 DERIVED

MeSH Terms

Conditions

Melanoma

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

Results Point of Contact

• Title: Lisa Franklin
• Organization: Istari Oncology

lfranklin@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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 19, 2018
• Study Start: November 26, 2018
• Primary Completion: March 23, 2021
• Study Completion: March 23, 2021
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Locations

US (1)