On October 3, 2022 Ascendis Pharma A/S (Nasdaq: ASND) reported completion of the dose-escalation portion and recommendation of the Phase 2 dose in transcendIT-101, a Phase 1/2 clinical trial to evaluate the safety and efficacy of TransCon TLR7/8 Agonist in locally advanced or metastatic solid tumors, alone or in combination with pembrolizumab (Press release, Ascendis Pharma, OCT 3, 2022, View Source [SID1234621613]). TransCon TLR7/8 Agonist is a novel investigational product candidate designed for sustained, localized release of resiquimod (a potent immune-response modifier with clinically demonstrated anti-tumor activity) with low systemic exposure. The abstract for the dose-escalation topline data was accepted for an oral presentation at SITC (Free SITC Whitepaper) 2022, the annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 8-12 in Boston.
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All patients in the dose escalation portion of the trial had advanced or metastatic solid-tumors and had progressed on prior treatments. In the next phase of the trial, the recommended Phase 2 dose of TransCon TLR7/8 Agonist will be evaluated in four cohorts focused on cancers where increased Toll-like receptor (TLR) activity has potential to improve adaptive immune activation and host defense against cancers. The cohorts include head and neck squamous-cell carcinoma (HNSCC); other HPV-associated cancers; melanoma; and cutaneous squamous cell carcinoma (cSCC). In this portion of the study, all participants will be treated every three weeks with intratumoral TransCon TLR7/8 Agonist in combination with intravenous pembrolizumab. Limits on prior lines of therapy vary by cohort.
"Our vision in oncology is to leverage TransCon technologies to turn the body’s immune system into a more potent anti-cancer therapeutic. In this first-in-human oncology trial, we are especially pleased to see TransCon hydrogel technology working as designed to achieve sustained intratumoral release of resiquimod over weeks while limiting systemic exposure," said Stina Singel, Senior Vice President, Head of Clinical Development, Oncology at Ascendis Pharma. "With a favorable safety profile and early signs of clinical activity observed, we are especially excited to be presenting topline dose-escalation data, including pharmacokinetic and biomarker data from injected and non-injected tumors, at the upcoming SITC (Free SITC Whitepaper) meeting. We are thankful to have the continued trust and engagement of patients and physicians working to transform the future of cancer care."
Later this year, Ascendis will initiate a clinical investigation of TransCon TLR7/8 Agonist intratumoral treatment in combination with TransCon IL-2 β/γ, the company’s product candidate designed for systemic activation of tumor-antigen specific cytotoxic cells.
About TransCon TLR7/8 Agonist
Immunotherapies can stimulate, intensify, and sustain the immune system’s natural ability to recognize and eliminate cancer cells, yet many patients do not respond to immunotherapies currently on the market, most of which are designed for intravenous administration and many of which have unfavorable toxicity profiles at therapeutically effective doses. TransCon TLR7/8 Agonist is an investigational long-acting prodrug of resiquimod, a small molecule agonist of Toll-like receptors (TLRs) 7 and 8 designed to provide sustained activation of intratumoral antigen-presenting cells driving tumor antigen presentation and induction of immune-stimulatory cytokines for weeks with a single intratumoral injection. TransCon TLR7/8 Agonist leverages the unique ability of Ascendis Pharma’s TransCon hydrogel technology to achieve sustained, localized release of resiquimod (a potent immune-response modifier with clinically demonstrated anti-tumor activity) in the injected tumor over weeks, where it is designed to steadily activate and intensify the body’s innate and adaptive immune responses to eradicate cancer cells in both injected and distal tumors, while maintaining low systemic drug exposure.