Phase 2 Study of Imprime PGG & Pembrolizumab in Subjects With Adv SCCHN Who Failed Pembro Monotherapy or Experiencing SD

NCT03246685 | Terminated Phase 2 FDA Drug

• 1 other identifier: BT-CL-PGG-HNC-1622MK3475PN-544
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To determine the Overall Response Rate (ORR) to Imprime PGG + pembrolizumab in subjects with advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) Safety: To characterize the safety of Imprime PGG + pembrolizumab given in combination Hypothesis: Restore (for subjects who have failed pembrolizumab mono therapy) or enhance (for subjects who actively experiencing SD) sensitivity to checkpoint inhibitors (CPI) by appropriate and effective stimulation of the subject's innate and adaptive immune systems by combining Imprime PGG with pembrolizumab. The study will require documenting at least 5 objective responses among the 38 subjects enrolled who have failed prior pembrolizumab monotherapy and at least 17 objective responses among the 49 subjects enrolled who are actively experiencing stable disease following at least 4 cycles (but no more than 8 cycles) of pembrolizumab monotherapy.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) to Imprime PGG + pembrolizumab using RECIST v1.1 criteria

  Within 18 months of last patient enrolled

Secondary Outcomes (6)

• Time to response (TTR) using RECIST v1.1 criteria

  Within 24 months of last patient enrolled

• Complete response rate (CRR) using RECIST v1.1 criteria

  Within 24 months of last patient enrolled

• Duration of overall response (DoR) using RECIST v1.1 criteria

  Within 24 months of last patient enrolled

• Progression-Free Survival (PFS) and PFS rate at 6 months and 1 year using RECIST v1.1 criteria

  6 months and 1 year after first dose and within 24 months of last patient enrolled

• Overall survival (OS) and OS rate at 1 year

  1 year after first dose and within 24 months of last patient enrolled

Other Outcomes (6)

• ORR based on irRECIST

  Within 24 months of last patient enrolled

• PFS based on irRECIST

  Within 24 months of last patient enrolled

• Correlate levels of baseline serum anti-β-glucan antibody (ABA) with objective response and treatment outcomes

  Within 24 months of last patient enrolled

Study Arms (2)

Pembrolizumab Failures

EXPERIMENTAL

Imprime PGG + Pembrolizumab

Biological: Imprime PGG; Drug: Pembrolizumab

Active Stable Disease on Pembrolizumab

EXPERIMENTAL

Imprime PGG + Pembrolizumab

Biological: Imprime PGG; Drug: Pembrolizumab

Interventions

Imprime PGG BIOLOGICAL

Imprime PGG is a soluble, β-1,3/1,6 glucan isolated from the cell wall of a proprietary Saccharomyces cerevisiae yeast strain. Imprime PGG acts as a Pathogen-Associated Molecular Pattern (PAMP). Imprime will be administered at a dose of 4 mg/kg IV over a 2-hour infusion time on Days 1, 8 and 15 of each 3-week treatment cycle.

Also known as: Imprime

Active Stable Disease on Pembrolizumab; Pembrolizumab Failures

Pembrolizumab DRUG

Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 protein. Pembrolizumab will be given at a fixed dose of 200 mg IV over 30 minutes on Day 1 of each 3-week treatment cycle after the Imprime infusion.

Also known as: Keytruda

Active Stable Disease on Pembrolizumab; Pembrolizumab Failures

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have signed an informed document prior to any study-specific procedures or treatment
• Be ≥ 18 years of age at time of consent
• Have histologically or cytologically confirmed diagnosis of SCCHN irrespective of PD-L1 status, which is either inoperable and recurrent, or metastatic
• Up to 3 prior chemotherapy regimens or metastatic disease
• Have either:
• Investigator determined assessment of disease progression after treatment with pembrolizumab monotherapy, OR
• Investigator determined assessment of current stable disease following completion of at least 4 cycles but no more than 8 cycles, of pembrolizumab monotherapy
• Have resolution of all previous treatment-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (less than or equal to Grade 2) or alopecia. If subject received major surgery or radiation therapy of \> 30 Gy, must have recovered from the toxicity and/or complications from the intervention.
• Have at least one radiologically measurable lesion as per RECIST v1.1 defined as a lesion that is at least 10 mm in longest diameter or lymph node that is at least 15 mm in short axis imaged by CT scan or MRI and obtained by imaging within 28 days prior to start of study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have peripheral blood levels of IgG anti-β-glucan antibody (ABA) of ≥ 20 mcg/mL as determined by an ELISA test within 90 days prior to start of study treatment
• Be willing to consider providing fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality, for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded block specimens are preferred to slides.
• Note: Information on 1 tumor biopsy sample is mandatory and is as follows: (1) To determine eligibility, historical (diagnostic) tumor biopsy official pathology report +/- an archival sample. Additional biopsy samples, preferably obtained from the same localized region, are highly desirable when feasible at the following time points: (2) Sample before the first dose of study treatment, (3) Sample after completion of Cycle 2 but before the start of Cycle 3 dosing, and (4) Sample either at the time of response or at the End of Study Visit (if no response).
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 14.3)
• Have life expectancy of 6 months or greater as determined by the treating physician
• Have adequate organ function (all screening labs should be performed within 15 days prior to study treatment):

You may not qualify if:

• Has disease that is suitable for local therapy administered with curative intent
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
• Has known history of active tuberculosis
• Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• Has known active Hepatitis B (eg, HBsAg reactive) or Hepatitis C (eg, HCV RNA \[qualitative\] is detected
• Has a history of clinically severe autoimmune disease, or history of organ transplant
• Has known hypersensitivity to baker's yeast
• Had previous exposure to Betafectin® or Imprime PGG
• Has severe hypersensitivity to pembrolizumab or any of its excipients
• Had a prior anti-cancer monoclonal antibody (other than pembrolizumab) within 30 days prior to start of study treatment, or failure to recover to CTCAE Grade 1 or better from the adverse events of prior therapies
• Had within 2 weeks prior to the first dose of study treatment, received prior chemotherapy, targeted small molecule therapy, or radiation therapy, or who has not recovered from adverse events due to a previously administered agent or major surgery
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF, or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment
• Has known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.

Sponsors & Collaborators

• HiberCell, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Northwestern Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2017
• First Posted: August 11, 2017
• Study Start: November 8, 2017
• Primary Completion: April 13, 2018
• Study Completion: April 13, 2018
• Last Updated: December 14, 2018

Record last verified: 2018-12

Locations

US (1)