R44CA306565

A Phase 2 trial of AXELOPRAN plus PEMBROLIZUMAB for the first-line treatment of recurrent/metastatic HNSCC that is PD-L1 positive (PD-L1CPS >1) - the proposed project will test if the addition of AXELOPRAN, a peripherally-restricted opioid antagonist, to standard of care PEMBROLIZUMAB will increase objective response rate vs. historic controls in recurrent or metastatic head & neck squamous cell carcinoma (R/M HNSCC) with a CPS≥1, who are also taking opioid analgesics to control cancer-related pain.

This is the first step of a development program that will seek approval for AXELOPRAN as an adjunctive therapy to immune checkpoint inhibitors in R/M HNSCC, and ultimately other solid tumors.

Pain is a common symptom of advanced cancer, and is particularly prevalent in R/M HNSCC due to the sensitive nature of the tissues affected.

Opioid analgesia is a vital cornerstone of adequate pain control, an imperative for patient quality of life.

However, growing evidence demonstrates that opioid analgesia interferes with checkpoint inhibitor efficacy, and this has recently also been shown in R/M HNSCC by our collaborators at the University of Pittsburgh.

A peripherally-restricted antagonist is an appealing strategy to address this problem, because it can block the peripheral actions of the opioid, which have been shown in a mouse model to impair checkpoint inhibitor efficacy, without impairing imperative patient pain control.

The proposed research plan will test the efficacy of AXELOPRAN in improving objective response rate per RECIST 1.1 by comparing against historic controls from University of Pittsburgh Medical Center who received opioid analgesia concomitantly to immune checkpoint inhibitors for R/M HNSCC.

It plans to enroll 18 patients in two stages: 5 patients for a futility analysis (where 1 response would show non-futility) and 13 further patients (where 7 responses out of 18 total patients would show significant improvement over a historical comparator of 11.4% ORR).

The proposed clinical study would also determine safety and tolerability of adding AXELOPRAN to PEMBROLIZUMAB in this population, which is a new study population and therapeutic combination for AXELOPRAN.

AXELOPRAN has previously been studied in >500 non-cancer patients for the indication of opioid-induced constipation, providing a known therapeutic dose that saturates peripheral receptors, and a clear expectation of potential adverse events that inform the safety and tolerability analysis.

If the study is successful, we anticipate further dialog with the FDA, with the goal of initiating, with registrational intent, a larger randomized controlled trial vs. placebo in the same target population.

Glycyx Mor

TO DEVELOP THE MEANS TO CURE AS MANY CANCER PATIENTS AS POSSIBLE AND TO CONTROL THE DISEASE IN THOSE PATIENTS WHO ARE NOT CURED. CANCER TREATMENT RESEARCH INCLUDES THE DEVELOPMENT AND EVALUATION OF IMPROVED METHODS OF CANCER TREATMENT THROUGH THE SUPPORT AND PERFORMANCE OF BOTH FUNDAMENTAL AND APPLIED LABORATORY AND CLINICAL RESEARCH. RESEARCH IS SUPPORTED IN THE DISCOVERY, DEVELOPMENT, AND CLINICAL TESTING OF ALL MODES OF THERAPY INCLUDING: SURGERY, RADIOTHERAPY, CHEMOTHERAPY, AND BIOLOGICAL THERAPY INCLUDING MOLECULARLY TARGETED THERAPIES, BOTH INDIVIDUALLY AND IN COMBINATION. IN ADDITION, RESEARCH IS CARRIED OUT IN AREAS OF NUTRITIONAL SUPPORT, STEM CELL AND BONE MARROW TRANSPLANTATION, IMAGE GUIDED THERAPIES AND STUDIES TO REDUCE TOXICITY OF CYTOTOXIC THERAPIES, AND OTHER METHODS OF SUPPORTIVE CARE THAT MAY SUPPLEMENT AND ENHANCE PRIMARY TREATMENT. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.395 - Cancer Treatment Research

National Cancer Institute (NCI) [HHS - NIH]

San Francisco, California 941212028 United States

Single Zip Code

PHS 2024-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required) (PA-24-246)