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)
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
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
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
Cohort Specific Inclusion Criteria (see § 9.5 Evaluation of Best Overall Response
9. Patients who have received at least 8 weeks of immunotherapy.
10. Patients have progressive disease based on RECIST 1.1 criteria
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.
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
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
10. Documented allergic or hypersensitivity response to any protein therapeutics (e.g.,
recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies,
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.