Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Head and Neck Neoplasms

Sarcoma

Skin Neoplasms

Skin Diseases

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Pembrolizumab

Immunomodulating Agents

Nivolumab

Durvalumab

Cemiplimab

Atezolizumab

Poly ICLC

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Interferons

Immunologic Factors

Open labeled, non randomized adaptive 2-stage design protocol. 21 study subjects were enrolled in stage I of the protocol. Up to an additional 60 patients. . Enrolled study subjects will receive Poly-ICLC (Hiltonol®) treatment alone or in combination with anti-PD-1 (Nivolumab, Pembrolizumab or Cemiplimab) or anti-PD-L1 (Atezolizumab or Durvalumab) over 6 months as defined in study treatment described below. MRI or CT imaging will be done per SOC at screening, 3 and 6-month time points.

For purposes of analysis patients enrolled in Stage II of this study will be prospectively identified at initial screening as belonging to statistical Cohorts A, B, or C, which are based on patient status with regard to aPD1/aPDL1 therapy at study entry, (PD, SD, or treatment naïve). For purposes of this study, patient status is considered to be the primary eligibility variable, although sub analyses will also consider histology and particular checkpoint blocker used when possible.

Wk 1 Days 1, 3 and 5: Poly-ICLC (Hiltonol®) 1 mg (0. 5 ml) IntraTumoral (priming treatment course). Weeks 2-25 Poly-ICLC (Hiltonol®) 1 mg (0.5 ml) IM twice a week with a 48-72 hour interval between the two injections, AND either:

No additional immunotherapy OR

ONLY ONE of the Anti-PD1 or anti-PDL-1 regimens will be administered, per manufacturer's dosing and clinical oncologist's discretion as follows: (Not to be Administered on the same day as Poly-ICLC \[Hiltonol®\]) Either Nivolumab, OR Pembrolizumab, OR Atezolizumab, OR Cemiplimab, OR Durvalumab

Hiltonol

Nina Bhardwaj, MD, PhD

David H Smith, MD

Kevin Staveley-O'Carroll, MD

Frederick P Smith, MD

The purpose of this study is to evaluate the safety of sequential intratumoral (IT) plus intramuscular (IM) Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC, Hiltonol®) for treatment of study subjects with accessible solid tumors, with or without checkpoint blockers. Enrolled study subjects will receive Poly-ICLC (Hiltonol®) treatment alone or in combination with anti-PD-1 (Nivolumab, Pembrolizumab or Cemiplimab) or anti-PD-L1 (Atezolizumab or Durvalumab) over 6 months as defined in study treatment described below. MRI or CT imaging will be done per SOC at screening, 3 and 6-month time points.

For purposes of analysis patients enrolled in Stage II of this study will be prospectively identified at initial screening as belonging to statistical Cohorts A, B, or C, which are based on patient status with regard to aPD1/aPDL1 therapy at study entry, (PD, SD, or treatment naïve) per section 11.5. For purposes of this study, patient status is considered to be the primary eligibility variable, although sub analyses will also consider histology and particular checkpoint blocker used when possible. Please see section 12 (Statistical Analysis) for further discussion.

Week 1 Days 1, 3 and 5: Poly-ICLC (Hiltonol®) 1 mg (0. 5 ml) IntraTumoral (priming treatment course).

Weeks 2-25:

1. Poly-ICLC (Hiltonol®) 1 mg (0.5 ml) IM twice a week with a 48-72 hour interval between the two injections, AND either:
2. No additional immunotherapy OR
3. ONLY ONE of the following Anti-PD1 or anti-PDL-1 regimens will be administered, per manufacturer's dosing and clinical oncologist's discretion as follows: (Not to be Administered on the same day as Poly-ICLC \[Hiltonol®\])

   * Either Nivolumab (Opdivo), OR
   * Pembrolizumab (Keytruda), OR
   * Atezolizumab (Tecentriq) OR
   * Cemiplimab (Libtayo) OR
   * Durvalumab (Imfinzi)

NOTE: It is recognized that some patients will have already been on anti-PD-1 or anti-PD-L1 at the time of study entry. Such patients will not have their checkpoint blocker therapy interrupted, but will be started on Poly-ICLC on week one, as above

If well tolerated they continue at full dose of 1 mg IM twice weekly through week 25. Anti-PD-1 or anti-PD-L1 per manufacturers package insert begins on week two and continues through week 25 or beyond per standard of care at physician's discretion. After the end of Poly-ICLC treatment at week 25, aPD1 or aPDL1 can be continued at the discretion of the patient and treating physician, per SOC, independent of this protocol.

At week 26 study subjects will be assessed and response determined using the RECIST 1.1 criteria. This will include measurement of accessible lesions as well as CT scan of the chest, abdomen and pelvis and extremities or neck to assess for response, using RECIST 1.1. MRI of the brain may also be obtained as part of clinical follow of their disease, if clinically indicated as per standard clinical protocol. Study subject's response will be defined as BOR (CR, PR, SD) or PD. If tumors are present and accessible, biopsies of the injected tumor as well as of a non-targeted/non-injected tumor will also be obtained at week 26.

Study subjects with CR, PR, or SD may be offered an additional treatment cycle depending on study subject's health status, costs and/or drug availability. At week 26 a repeat tumor assessment will be performed, an optional biopsy may be performed.

Follow up Period:

After completion of study treatment, study subjects may be contacted by telephone at least twice over 12 months, or longer with patient consent to inquire on their health status (e.g., alive, remission, progressive disease, on new cancer treatment). Study subjects with an initial tumor response but then long-term recurrence during the follow up period may be offered additional cycles of treatment depending on the study subject's health status, costs and/or drug availability.

In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol®

In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC): An Adaptive, Multicenter, Phase II Clinical Study

Wk 26 study subject's response will be defined as BOR (CR, PR, SD) or PD.

Week 26 tumor assessment will be performed, an optional biopsy may be performed.

Serial blood samples collected at certain time points and processed and used to evaluate humoral and cellular immunity induced by IT and IM polyICLC injections

In the present protocol, we propose to induce both innate and adaptive cellular immune mechanisms with IT injections of poly-ICLC (Nierkens, den Brock et al. 2008)

Bi-dimensional measurements will be performed on injected and non-injected lesions at the indicated time points in the study calendar.

Up to 5 visible deep measureable lesions will be designated as Target Lesions (index lesions)

Survival and disease control/progression-free survival (PFS) will be estimated using Kaplan-Meir curves.

National Institutes of Health (NIH)

Icahn School of Medicine at Mount Sinai

Bay Hematology Oncology

National Cancer Institute (NCI)

University of Missouri-Columbia

Chevy Chase Regional Cancer Care Associates LLC

Dermatologic Surgery Center of Washington LLC and Skin Cancer Treatment Center

Oncovir, Inc.

Carcinoma

Carcinoma, Squamous Cell

Breast Neoplasms

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Basal Cell

Neoplasms, Basal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Enrolled patients will receive two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle.

Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks.

Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms.

Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan.

Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks.

Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms.

Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation.

Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy

Follow Up via phone every 3 months for 30months, after completion of treatments.

Poly-ICLC

The purpose of this study is to test the safety of a course of injections containing Poly-ICLC in patients with advanced solid tumors that can be easily and safely reached with a needle.

Poly-ICLC is a compound that has been used to help the body in its fight against cancer.

We hypothesize that this therapeutic in-situ autovaccination strategy is comprised of three immunomodulatory steps. The first is the innate immune local tumor killing induced by intratumoral Hiltonol (via NK, TNF, etc). A very close second step is optimal Th1-weighted priming through the in-situ combination of the poly-ICLC danger signal with the tumor antigens released in step 1 and further processed and cross-presented by poly-ICLC activated mDC, etc. The repeated administration of the Hiltonol danger signal IT in the context of the patient's own tumor antigens and in a way that mimics a natural viral infection may be critical to this step. Once the system is optimally primed, the third step is targeting and maintenance of the immune response and its facilitation at remote tumor sites with IM poly-ICLC through chemokine release, inflammasome activation and other costimulatory factors.

Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC)

Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC): A Phase II Clinical Study

Patients who are alive on the date of closing follow-up, or 30 months after completing all study treatments, will be censored on that date

Progression-free survival defined as the time in weeks from study entry until tumor progression defined using the Wolchok criteria or death. Patients who are alive and free from progression on the date of closing follow-up will be censored on that date.

In order to minimize the potential for misdiagnosis of pseudoprogression, related to early inflammation, tumor measurement for determination of progression will be made at the earliest at 26 weeks.

Induction of innate and/or an adaptive, specific anti-tumor T cell immune response in the injected tumor lesion and also systemically.

Nina Bhardwaj

Director, Immunotherapy Program

Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle.

Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks.

Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms.

Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan.

Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks.

Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation.

Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy

Participants With Stage 4 Cancer

Age, Continuous

Sex: Female, Male

Dr. Nina Bhardwaj

Progression-free Survival

study terminated early, data not collected. study terminated before all study visits completed. this 24 month visit was not done.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol®	NCT02423863	Melanoma Head and Neck C... Sarcoma Non-Melanoma Sk...	Hiltonol	18 Years -	Oncovir, Inc.
Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC)	NCT01984892	Melanoma Squamous Cell C... Squamous Cell C... Sarcoma of the ... Basal Cell Canc... Breast Cancer	Poly-ICLC	14 Years -	Icahn School of Medicine at Mount Sinai
In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol®	NCT02423863	Melanoma Head and Neck C... Sarcoma Non-Melanoma Sk...	Hiltonol	18 Years -	Oncovir, Inc.

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