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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04690699
Recruitment Status : Not yet recruiting
First Posted : December 31, 2020
Last Update Posted : June 14, 2021
Information provided by (Responsible Party):
Istari Oncology, Inc.

Brief Summary:
This is a Phase 1/2, open-label, multi-center, single arm basket study evaluating the administration of PVSRIPO ± 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. Bladder Cancer has been selected as the first tumor specific cancer of interest for enrollment.

Condition or disease Intervention/treatment Phase
Solid Tumor Bladder Cancer Biological: PVSRIPO Biological: Anti-PD-1 / L1 Phase 1 Phase 2

Detailed Description:

For each solid tumor cancer, a Phase 1 evaluation of the safety and tolerability of PVSRIPO monotherapy intratumoral injections will be completed prior to initiation of enrollment in the Phase 2 portion of the study where the anti-tumor efficacy of PVSRIPO in combination with anti PD 1/L1 therapy will be assessed.

Bladder Cancer has been selected as the first solid tumor cancer of interest. Two cohorts of patients will be enrolled: Cohort A will include cisplatin-ineligible patients with resectable MIBC being treated in the neoadjuvant setting and Cohort B will include patients with bladder cancer being treated in the 1st/2nd line unresectable/metastatic setting. The Phase 1 portion of the study (PVSRIPO monotherapy) will only enroll patients from Cohort A. Once the Data Safety Monitoring Committee (DSMC) has evaluated the safety of the patients enrolled in the Phase 1 portion of the study and determined it is "safe to proceed", then the Phase 2 portion of the study (PVSRIPO/pembrolizumab combination) will open. Approximately 6 patients will be enrolled in Phase 1 (Cohort A), and 50 patients will be enrolled in Phase 2 (25 patients in Cohort A and 25 patients in Cohort B).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 155 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: LUMINOS-103: A Basket Trial Evaluating the Safety and Efficacy of PVSRIPO and PVSRIPO in Combination With Anti-PD-1/L1 Checkpoint Inhibitors in Patients With Advanced Solid Tumors
Estimated Study Start Date : June 30, 2021
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm 1: PVSRIPO and Anti-PD-1/L1 Therapy
Subjects will be treated with a combination of PVSRIPO and an FDA-approved anti-PD-1/L1 therapy, the choice of which will be determined based on the solid tumor cancer of interest and specified in the associated tumor specific appendix.
Biological: PVSRIPO
PVSRIPO administered via intertumoral injection.

Biological: Anti-PD-1 / L1
Anti-PD-1 / L1 Therapy administered per package insert instructions.

Primary Outcome Measures :
  1. Safety and Tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE [ Time Frame: 24 months ]
    To evaluate the safety and tolerability of PVSRIPO administered as monotherapy and in combination with an anti-PD-1/L1 therapy.

  2. Tumor Response measured by RECIST 1.1 [ Time Frame: 24 months ]
    To evaluate the tumor response to PVSRIPO administered in combination with an anti-PD-1/L1 therapy.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Master Protocol Inclusion Criteria:

  1. 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.
  2. Age ≥ 18 years of age at the time of signing the informed consent.
  3. 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.

  4. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  5. 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.

  6. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
  7. 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
    • Serum total bilirubin ≤1.5 x ULN OR direct bilirubin <ULN for patients with total bilirubin > 1.5 x ULN
    • For patients not receiving therapeutic anticoagulation: international normalized ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT) (or activated partial thromboplastin time [aPTT]) ≤ 1.5 x ULN
  8. Resolution of nonhematologic toxicities from prior therapy or surgical procedures to

    ≤ Grade 1 or baseline (except alopecia).

  9. Contraceptive use by men or women of childbearing potential should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Master Protocol Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. 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 PVSRIPO), myocardial infarction (≤ 6 months before the first dose of PVSRIPO), 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]).
  5. 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.
  6. 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.
  7. 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
  8. 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.
  9. Uncontrolled pleural effusion, pericardial effusion, or ascites; patients with indwelling catheters (eg, PleurX®) are allowed.
  10. Known serious active infection (eg, human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis, etc.).

    • Participants with a negative hepatitis B surface antigen (HBsAg) test and a positive total hepatitis B core antibody (HBcAb) test are allowed.
    • History of positive hepatitis C virus (HCV) antibody test, but negative HCV RNA test is allowed.
    • Participants with a historical positive HIV test are not allowed.
  11. Treatment with systemic immunosuppressive medication within 28 days of Cycle 1 Day 1, with the following exceptions:

    • Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (eg, 48 hours of corticosteroids for a contrast allergy) are eligible.
    • Patients receiving mineralocorticoids (eg, fludrocortisone), or systemic prednisone equivalent corticosteroid doses of < 10 mg per day are eligible for the study.
  12. Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation.
  13. Receipt of any live, attenuated vaccines within 28 days of Cycle 1 Day 1. Vaccination to prevent symptomatic SARS-CoV-2 infection is allowed as long as the vaccine is NOT a live attenuated vaccine (e.g. adenovirus-based constructs); however, the vaccine should be administered ≥ 1 week before or after a PVSRIPO injection.
  14. Known hypersensitivity to any of the drugs used in this study.
  15. Pregnant or lactating women.
  16. History of human serum albumin allergy.
  17. History of neurological complications due to PV infection.
  18. History of agammaglobulinemia.
  19. Legal incapacity or limited legal capacity.
  20. Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator's opinion could affect the patient's safety, compliance, or follow-up in the protocol.

Bladder Cancer Specific Inclusion Criteria:

Both Cohorts:

  1. Histologically or cytologically confirmed urothelial carcinoma arising from the lower urinary tract and amenable to intratumoral injection. Both urothelial carcinoma and mixed urothelial/non-urothelial cell histologies are allowed. Patients with pure non-urothelial histologies are excluded.
  2. Measured or calculated (per institutional standard) creatinine clearance ≥ 45 ml/min (GFR can also be used in place of creatinine clearance).
  3. A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh biopsy if collection date of archival specimen > 6 months prior to Cycle 1 Day 1) 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.

Cohort A:

  1. Clinical stage T2-T4a, N0, M0 by computed tomography (CT) abdomen/pelvis urogram or magnetic resonance imaging (MRI) abdomen/pelvis urogram.
  2. Have refused or are ineligible for cisplatin-based therapy, defined as meeting one of the following criteria. Note: the master protocol excludes patients with Eastern Cooperative Oncology Group (ECOG) ≥ 2 or congestive heart failure New York Heart Association (NYHA) class ≥ II.

    1. Glomerular filtration rate (GFR) < 60 mL/min calculated per institutional standard
    2. Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 Grade ≥ 2 hearing loss
    3. CTCAE v 5.0 Grade ≥ 2 peripheral neuropathy NOTE: the hearing loss and peripheral neuropathy criteria are exceptions to the criterion in the master protocol stating all nonhematologic toxicities from prior therapy or surgical procedures be ≤ Grade 1 or baseline.
  3. Fit and planned for cystectomy (according to local guidelines).
  4. Have received no prior systemic therapy for MIBC.
  5. Must have post-TURBT site/lesion amenable for injection via cystoscopy (determined by the Investigator).
  6. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is NOT required. This is an exception to the inclusion criterion outlined in the master protocol.

Cohort B:

  1. Unresectable locally advanced or metastatic bladder cancer

    1. T4b, any N
    2. Any T, N 2-3
    3. Any T, any N, M1
  2. Have received no more than one prior line of systemic therapy in the unresectable/metastatic setting; systemic therapy given in the neoadjuvant or adjuvant setting where the last date of administration is > 12 months prior to the date of recurrence is allowed.
  3. Must have lesion that is amenable to injection via cystoscopy of intact bladder (per the Investigator) and at least one measured dimension ≥ 1 cm.
  4. Must have at least 1 lesion amenable to biopsy a. The lesion must be safely accessible as determined by the investigator and should not be located at sites that require significant risk procedures to biopsy. Examples of sites considered to be of significant risk include but are not limited to: biopsies of the brain, lung, mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel wall.

Bladder Cancer Specific Exclusion Criteria:

Both Cohorts:

  1. Patients who require antiplatelet agents (including low dose aspirin) or therapeutic anticoagulation and cannot discontinue these agents safely during the 3 days prior to, day of, and 3 days after intratumoral injection of PVSRIPO.
  2. Received prior treatment with a PD-1/L1 inhibitor for any malignancy including early-stage bladder cancer.
  3. Received prior treatment with an agent directed to another stimulatory or co-inhibitory T-cell receptor.

Cohort A:

1. TURBT does not qualify as a major surgery/procedure or open biopsy (see exclusion criterion in master protocol).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04690699

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Contact: Kristin Orr 9193950132
Contact: Lisa Franklin

Sponsors and Collaborators
Istari Oncology, Inc.
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Responsible Party: Istari Oncology, Inc. Identifier: NCT04690699    
Other Study ID Numbers: LUMINOS-103
First Posted: December 31, 2020    Key Record Dates
Last Update Posted: June 14, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases