Clinical Trials /

Poly-ICLC (Hiltonol) and Anti-PD1 or Anti-PD-L1

NCT03721679

Description:

This is an open labeled, non-randomized adaptive pilot study. The study interventions involved in this study are: Poly-ICLC (Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose, also known as Hiltonol®) treatment in combination with anti-PD-1 (Nivolumab, Cemiplimab or Pembrolizumab) or anti-PD-L1 (Atezolizumab or Durvalumab)

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Poly-ICLC (Hiltonol) and Anti-PD1 or Anti-PD-L1
  • Official Title: Poly-ICLC (Hiltonol®) Plus Anti-PD1 or Anti-PD-L1 in Unresectable Solid Cancers An Adaptive Phase I/II Clinical Pilot Study

Clinical Trial IDs

  • ORG STUDY ID: ONC2018-001
  • NCT ID: NCT03721679

Conditions

  • Solid Cancer

Interventions

DrugSynonymsArms
Poly-ICLC combination treatment with aPD-1 (Nivolumab or Pembrolizumab) or aPD-L1 (Atezolizumab or Durvalumab) over 6 monthsSame as abovePoly-ICLC treatment combination aPD-1or aPD-1L1

Purpose

This is an open labeled, non-randomized adaptive pilot study. The study interventions involved in this study are: Poly-ICLC (Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose, also known as Hiltonol®) treatment in combination with anti-PD-1 (Nivolumab, Cemiplimab or Pembrolizumab) or anti-PD-L1 (Atezolizumab or Durvalumab)

Detailed Description

      This research study is a PhaseI/II clinical trial investing a combination of targeted
      therapies as possible treatment for advanced solid cancers

      FDA has not yet approved Poly-ICLC as treatment for diseases in this study

      Pembrolizumab, Nivolumab, Atezolizumab, Cemiplimab and Durvalumab are now FDA approved for
      certain patients with multiple cancer types.

      The study is designed to evaluate the safety of intramuscular (IM) Polyinosinic-polycytidylic
      acid stabilized with polylysine and carboxymethylcellulose (Poly-ICLC, Hiltonol®) in
      combination with Anti-PD-1 or Anti-PD-L1 for treatment of study subjects with advanced solid
      cancers.
    

Trial Arms

NameTypeDescriptionInterventions
Poly-ICLC treatment combination aPD-1or aPD-1L1ExperimentalWeeks 1 and 2: Poly-ICLC (Hiltonol®) 1 mg (0.5 ml) IM ONLY twice a week with a 48-72 hour interval between the two injections Weeks 3-25: Poly-ICLC (Hiltonol®) 1 mg (0.5 ml) IM twice a week with a 48-72 hour interval between the two injections, AND ONLY 1 of the following regimens will be administered, per manufacturer's dosing and clinical oncologist's discretion as follows: Nivolumab (Opdivo), OR Pembrolizumab (Keytruda), OR Cemiplimab (Libtayo) OR Atezolizumab (Tecentriq) OR Durvalumab (Imfinzi) Follow up: After completion of treatment subjects may be contacted by telephone at least twice over 12 months, or longer with patient consent, in order to inquire on their health status (e.g., in remission, progressive disease, on new cancer treatment).
  • Poly-ICLC combination treatment with aPD-1 (Nivolumab or Pembrolizumab) or aPD-L1 (Atezolizumab or Durvalumab) over 6 months

Eligibility Criteria

        Inclusion Criteria

          1. Histologically confirmed diagnosis of Solid Cancer, independent of PD-L1 tumor status.

          2. Patients must be 18 years of age or older.

          3. Unresectable disease. Patients with resectable disease but who refuse surgery may be
             enrolled after a documented consultation with a surgeon.

          4. Radiologically or visually measurable disease that is at least 10mm in longest
             dimension, AND/OR with elevated disease specific serum markers that can be followed
             for progression (eg CA-125, AFP, PSA, CA19-9 or CEA)

          5. ECOG performance status of ≤ 2.

          6. Acceptable hematologic, renal and liver function as follows:

             A) Absolute neutrophil count > 1000/mm3 B) Platelets > 50,000/mm3, C) Creatinine ≤ 2.5
             mg/dl, D) Total bilirubin ≤ 1.5 mg/dl, unless due to tumor or Gilbert's syndrome E)
             Transaminases ≤ 2 times above the upper limits of the institutional normal. F) INR<2
             if off of anticoagulation. Patients on anticoagulation therapy with an INR>2 may be
             enrolled at the discretion of the investigator if they have not had any episodes of
             severe hemorrhage.

          7. Patients must be able to provide informed consent.

          8. Patients with the potential for pregnancy or impregnating their partner must agree to
             follow acceptable birth control methods to avoid conception. Contraception must be
             continued for at least 2 months following the last dose of Poly-ICLC. Women of
             childbearing potential must have a negative pregnancy test. While animal reproductive
             studies have been negative, the simulated viral infection and anti-proliferative
             activity of this experimental drug may theoretically affect the developing fetus or
             nursing infant.

             Cohort Specific Inclusion Criteria (see § 9.5 Evaluation of Best Overall Response
             (BOR)

             Cohort A

          9. Patients who have received at least 8 weeks of immunotherapy.

         10. Patients have progressive disease based on RECIST 1.1 criteria

             Cohort B)

         11. Patients who have received at least 8 weeks of aPD1 or aPDL1 immunotherapy.

         12. Patients have stable disease or a partial response based on RECIST 1.1 criteria.

             Cohort C)

         13. Patients who have not received an anti-PD-1 or anti-PD-L1 agent, but who carry a
             diagnosis for which one of these agents is the SOC.

         14. Patients willing to delay receipt of first dose of anti-PD-1 or anti-PD-L1 until after
             the receipt of their first two doses of intramuscular Poly-ICLC

        Exclusion Criteria

          1. Patients may not be receiving any other investigational agents.

          2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection requiring antibiotics (exception is a brief (≤10days) course of antibiotics
             to be completed before initiation of treatment), symptomatic congestive heart failure,
             unstable angina pectoris, or psychiatric illness/social situations that would limit
             compliance with study requirements.

          3. Patients must not be pregnant or nursing due to the potential for congenital
             abnormalities and the potential of this regimen to harm nursing infants.

          4. Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy
             or any other form of immunosuppressive therapy within 7 days prior to the first dose
             of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose)
             equivalent to ≤ 10mg prednisone will not be excluded.

          5. Has active autoimmune disease that has required systemic treatment in the past 1 year
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.

          6. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the patient's
             participation for the full duration of the trial, or is not in the best interest of
             the patient to participate, in the opinion of the treating Investigator.

          7. HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART)
             regimen, or with <200 CD4+ T cells/microliter in the peripheral blood.

          8. Has known active Hepatitis B (e.g., HBV detected by elevated PCR or active Hepatitis C
             (e.g., HCV RNA [qualitative] is detected).

          9. History of allogeneic hematopoietic cell transplantation or solid organ
             transplantation.

         10. Documented allergic or hypersensitivity response to any protein therapeutics (e.g.,
             recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies,
             receptor traps)

         11. Principal investigator believes that for one or multiple reasons the patient will be
             unable to comply with all study visits, or if they believe the trial is not clinically
             in the best interest of the patient.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor assessment
Time Frame:6 month timepoint compared to baseline
Safety Issue:
Description:Response and progression will be evaluated in this study. Tumor Response will be assessed by the RECIST 1.1 Criteria. Response is defined as CR, PR or SD over a period of at least 4 weeks. Changes in the sum of the two largest perpendicular diameters (SPD) of the tumor lesions, or the shortest diameter in the case of malignant lymph nodes are used in the RECIST 1.1 criteria. Study subjects with progressive disease will be evaluated to determine whether the progression causes symptoms and/or functional decline and study subjects with non-clinically relevant progression of disease may remain on study at the investigator's discretion.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oncovir, Inc.

Trial Keywords

  • Immunotherapy
  • Vaccine Therapy

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