ACTIVE_NOT_RECRUITING

Ph I/II Trial of Systemic VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Select Solid Tumors

Talk to us

Conditions

Solid TumorNon Small Cell Lung CancerNeuroendocrine CarcinomaRenal Cell Carcinoma (RCC)NSCLCNECRCCNon-small cell lung cancerNeuroendocrineRenal Cell

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The safety run-in portion of this study is designed to identify the optimal dose of VSV-IFNβ-NIS in combination with pembrolizumab in patients with solid tumors and follows the 3+3 design. The expansion portion will use one-sample binomial designs to assess the efficacy of the combination in patients with refractory NSCLC or NEC. The optimal dose (RP2D) determined in the dose escalation portion of the trial will be used for the expansion portion. The study has been conducted with a dose of 1.7 × 1010 as the recommended phase II dose in an expansion cohort of 10 patients with NSCLC. However, current data suggests that VSV-IFNβ-NIS doses of up to 1.7 × 1011 is safe and likely more efficacious. Thus, this study will test a second VSV-IFNβ-NIS dose level, 1.0x1011 TCID50. A safety assessment will be carried out after 3 patients are enrolled. If this dose schedule is well tolerated and virus PK are not negatively impacted, both the NSCLC and NEC expansion cohorts will open using this dose schedule. If 2 of the first 3 patients or 2 of the first 6 patients experience a DLT, the dose will be de-escalated to 5 x 1010. The safety run-in/dose escalation portion of this study is expected to require a minimum of 3 patients and a maximum of 18 patients (6 patients per dose level). The expansion portion of this study is expected to require a minimum of 10 per cohort. The NSCLC and NEC patients enrolled at the identified optimal dose in the dose escalation cohort would be included in the dose expansion cohort if they are evaluable for the primary endpoint in the expansion portion (4 dose escalation patients at the optimal dose are expected to roll over to the expansion). Additionally, up to 16 Renal Cell Carcinoma (RCC) patients will be treated in the expansion cohort. This will permit up to 86 treated patients.

Official Title

Phase 1-2 Trial of Systemically Administered VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Selected Solid Tumors

Quick Facts

Study Start:2019-04-09
Study Completion:2025-09-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT03647163

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Histologically confirmed diagnosis of:
  2. * Arm 1: dose level 1 and below: Advanced and/or metastatic solid tumors for which no existing options are felt to provide clinical benefit
  3. * Arm 2: dose level 2: Advanced and/or metastatic NSCLC OR NEC in which radiological progression has been demonstrated during therapy with a PD-1/PD-L1 immune checkpoint inhibitor, and for which no existing options are felt to provide clinical benefit.
  4. * Arm 3: Advanced and/or metastatic NEC in which radiological progression has been demonstrated during therapy with a PD-1/PD-L1 immune checkpoint inhibitor, and for which no existing options are felt to provide clinical benefit.
  5. * Arm 4: Advanced and/or metastatic NSCLC in which radiological progression has been demonstrated during therapy with a PD-1/PD-L1 immune checkpoint inhibitor, and for which no existing options are felt to provide clinical benefit.
  6. * Arm 5: NEC: poorly differentiated NEC (large or small cell, or not further specified) with progressive disease following at least one prior line of systemic therapy.
  7. * Arm 6: RCC: histologically confirmed diagnosis of advanced or metastatic RCC, including all IMDC risk categories (favorable, intermediate, and poor risk).
  8. * Measurable disease based on RECIST 1.1. The first 3 patients in the safety run-in phase do not need measurable disease. Part C: advanced NEC (neuroendocrine carcinoma based on histopathology according to WHO criteria. Patients with small cell carcinoma, large cell neuroendocrine carcinoma, and neuroendocrine carcinoma not otherwise specified, of any primary organ are eligible in which radiological progression has been demonstrated during therapy with a PD-(L)1 immune checkpoint inhibitor, and for which no existing options are felt to provide clinical benefit.
  9. * Performance status of 0 or 1 on the ECOG Performance Scale.
  10. * Life expectancy of \>3 months if not on active anti-cancer therapy
  11. * Willingness to provide biological samples required for the duration of the study including a fresh tumor biopsy sample.
  12. * Adequate organ function using predefined laboratory values obtained ≤14 days prior to registration.
  13. * Negative pregnancy test for female patients of childbearing potential
  14. * Absence of active CNS involvement. NOTE: Pre-enrollment imaging of asymptomatic patients not mandatory
  15. * Ability to provide written informed consent.
  16. * Willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
  1. * Availability of and patient acceptance of curative therapy.
  2. * Recent or ongoing serious infection, including:
  3. 1. Any active Grade 3 or higher (per the NCI CTCAE, version 4.03) viral, bacterial, or fungal infection within 2 weeks of registration.
  4. 2. Known seropositivity for or active infection by the human immunodeficiency virus (HIV).
  5. 3. Acute hepatitis B or acute hepatitis C. Patients with chronic hepatitis B or hepatitis C may be enrolled provided their liver function is adequate as per section 3.17
  6. 4. Known history of active TB (Bacillus tuberculosis).
  7. * Any serious health condition, which, in the opinion of the investigator, would place the patient at undue risk from the study, including uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 3 months) or neurological disorder (e.g., seizure disorder active within 3 months)
  8. * Prior therapy within the following timeframe before the planned start of study treatment as follows:
  9. * Chemotherapy, small molecule inhibitors, radiation, interventional radiology procedure, and/or other investigational agent: ≤3 weeks or 5 half-lives, whichever is shorter
  10. * Other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or experimental therapies: ≤4 weeks (≤3 weeks with documented disease progression)
  11. * Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization. Subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of randomization are strongly encouraged to receive palliative radiotherapy prior to randomization.
  12. * NSCLC patients only: prior chemotherapy or immunotherapy or a combination of chemotherapy and immunotherapy for stage IV NSCLC.
  13. * RCC patients:
  14. * New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or SVT) (Appendix II).
  15. * Any known or suspected active organ-threatening autoimmune disease, such as inflammatory bowel disease, autoimmune hepatitis, lupus, or pneumonitis, with the exception of hypothyroidism and type 1 diabetes that are controlled with treatment.
  16. * Immunodeficiency or immunosuppression, including systemic corticosteroids at \>10mg/day prednisone or equivalent within 1 week prior to planned start of study treatment
  17. * History of severe immune-mediated adverse reaction to immune checkpoint inhibitors.
  18. * Toxicities from previous therapies that have not resolved to a grade 1 or less.
  19. * History of non-infectious pneumonitis that required steroids, or current pneumonitis, or carcinomatous meningitis, or interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  20. * High volume disease, as assessed clinically via parameters such as radiologic impression and tumor markers or LDH.
  21. * Portal vein thrombosis involving more than intrahepatic portal vein branches: thrombosis of the right or left portal vein branch or the bifurcation, partial or complete obstruction of the portal vein trunk.
  22. * Known concurrent malignancy that is progressing or requires active treatment. EXCEPTIONS: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in-situ cervical cancer that has been treated with curative intent, prostate cancer confined to the prostate gland with Gleason score \<6 or PSA \<1, as well as any stage I cancer treated with curative intent or any prior cancer with a disease-free interval of ≥3 years.
  23. * Other concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-FDA approved indication and in the context of a research investigation)).
  24. * Neuroendocrine neoplasms described as "well-differentiated" or "moderately differentiated" on pathologic review, or reported as "carcinoid", i.e., not true poorly differentiated neuroendocrine carcinoma \[Nagtegaal 2020\].
  25. * Has received a live vaccine within 30 days of planned start of study treatment. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and are NOT allowed.
  26. * Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  27. * Pregnant women or women of reproductive ability who are unwilling to use highly effective contraception
  28. * Nursing women
  29. * Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment.
  30. * Prisoners or subjects who are involuntarily incarcerated.
  31. * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Contacts and Locations

Principal Investigator

Alex Adjei, MD, PhD
PRINCIPAL_INVESTIGATOR
The Cleveland Clinic
Patrick McGarrah, MD
PRINCIPAL_INVESTIGATOR
Mayo Clinic

Study Locations (Sites)

Mayo Clinic
Rochester, Minnesota, 55905
United States
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, 44195
United States

Collaborators and Investigators

Sponsor: Vyriad, Inc.

  • Alex Adjei, MD, PhD, PRINCIPAL_INVESTIGATOR, The Cleveland Clinic
  • Patrick McGarrah, MD, PRINCIPAL_INVESTIGATOR, Mayo Clinic

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-04-09
Study Completion Date2025-09-30

Study Record Updates

Study Start Date2019-04-09
Study Completion Date2025-09-30

Terms related to this study

Keywords Provided by Researchers

  • NSCLC
  • NEC
  • RCC
  • Non-small cell lung cancer
  • Neuroendocrine
  • Renal Cell

Additional Relevant MeSH Terms

  • Solid Tumor
  • Non Small Cell Lung Cancer
  • Neuroendocrine Carcinoma
  • Renal Cell Carcinoma (RCC)