SEATTLE & SOUTH SAN FRANCISCO, Calif.—Giving it more data to drive support solidly behind continuation of its CMB305 and G100 programs, clinical-stage oncology-focused immunotherapy company Immune Design in February reported positive top-line data from three ongoing Phase 1 oncology studies.
This follows news the month before that the U.S. Food and Drug Administration (FDA) had granted Orphan Drug designations for LV305 and G305 for the treatment of soft tissue sarcoma. LV305 and G305 are the complementary agents that comprise CMB305, Immune Design’s “prime boost” cancer immunotherapy product candidate—the company touts that CMB305 is, in fact, a first-in-class prime-boost immunotherapy targeting NY-ESO-1 tumors.
So, let’s start with the data from a completed first-in-human dose-escalation study and an early subset of patients from an expansion study of CMB305 as a single agent in patients with cancers expressing the NY-ESO-1 tumor antigen, which revealed:
- CMB305 seems to be safe, without dose-limiting toxicities
- A significant subset of CMB305-treated patients had NY-ESO-1-specific CD8 T cell responses that were generated or increased after therapy
- Patients who did respond immunologically had a greater degree of antigen-specific T cell response than that previously reported in a Phase 1 study of LV305 alone, which is consistent with the intent of the prime-boost approach
- Preliminary clinical benefit in the form of progression-free rate was observed in patients with soft tissue sarcoma.
Next, there is data from the expansion study following the previously reported dose escalation study of LV305 in patients with tumors expressing NY-ESO-1, which shows a consistently favorable safety profile, consistent immune response rate and improved clinical benefit profile.
Finally, moving away from data realted to CMB305 or one of its components, there were top-line results from the completed pilot trial of G100—Immune Design’s intratumoral immune activation approach to treating cancer—with local radiation in patients with Merkel cell carcinoma. Those data indicated:
- Safety was consistent with that originally reported, demonstrating an acceptable profile alone or in combination with local radiation
- G100 significantly altered the tumor microenvironment, causing inflammation and transforming tumors to a “hot” state in G100-responding patients
- Clinical benefit remained constant with the full patient set.
Abstracts for each of these three Phase 1 studies have been submitted for presentation at the American Society of Clinical Oncology Annual Meeting to be held in June.
“The accumulating data, including this new set, clearly supports proceeding with the clinical development of our two first products, CMB305 and G100, each activating the antitumor immune response by targeting a predefined tumor antigen or neo-antigens, respectively,” said Dr. Carlos Paya, president and CEO of Immune Design. “The initiation of randomized studies in which we are combining our two products with inhibitors of the PD-1/L1 axis through our collaborations with Genentech and Merck will provide the evidence as to how novel products that activate the immune system and aim to make tumors 'hot' add or synergize with checkpoint inhibitors.”
CMB305 is an immuno-oncology product candidate that involves the sequential dosing of two active agents, LV305 and G305. LV305 is a hybrid vector from the Immune Design’s ZVex discovery platform that specifically targets dendritic cells in vivo and delivers the RNA for NY-ESO-1, enabling the dendritic cells to express the entire tumor antigen and potentially induce a diverse set of cytotoxic T lymphocytes (CTLs) targeting NY-ESO-1 in tumors. G305, in contrast, is designed to boost the CTL response via the induction of antigen-specific CD4 “helper” T cells. G305 consists of recombinant NY-ESO-1 protein formulated with a proprietary synthetic small molecule called glucopyranosyl lipid A (GLA), the novel TLR4 agonist at the core of Immune Design’s GLAAS platform.
CMB305 is intended to be an “off-the-shelf” therapy that does not require patient-specific manufacturing or ex-vivo manipulation of patient samples. Immune Design has conducted prior studies to establish the safety and individual immunologic activity of LV305 and G305. CMB305 is currently being evaluated in a Phase 1b trial in patients with locally advanced, relapsed or metastatic solid cancers whose tumors express NY-ESO-1 and a randomized Phase 2 trial of CMB305 combined with Genentech’s investigational cancer immunotherapy atezolizumab (anti-PD-L1) in patients with soft tissue sarcoma, pursuant to a collaboration with Genentech.
As for G100, Immune Design’s intratumoral immune activation approach to treating cancer, which is expected to directly activate dendritic and other antigen presenting cells near the tumor, it may enhance the function of preexisting CTLs and create both a local and systemic immune response against neo-antigens. G100 is a product of the company’s GLAAS platform. G100 also has potential therapeutic utility in any accessible tumor and will be investigated in combination with local radiation and Merck’s anti-PD-1 agent, Keytruda, in a randomized study in patients with follicular non-Hodgkin's lymphoma, pursuant to a collaboration with Merck.
ZVex and GLAAS are Immune Design’s complementary discovery platforms designed to activate and expand the immune system’s natural ability to create tumor-specific CTLs in vivo. Immune Design’s product candidates generated from the ZVex and GLAAS discovery platforms have the potential to target multiple types of cancers, the company says on its website. While the two platforms have utility individually Immune Design notes: “An exciting aspect of the Immune Design discovery platforms is the mechanistical synergy of ZVex + GLAAS. When combined, ZVex plus GLAAS are designed to yield a more potent immune response called a heterologous prime boost ... This combination of two novel technologies may result in the generation of a first-in-class and best-in-class approach to generating and expanding CTLs. CMB305 is the first combination product candidate that will combine ZVex- and GLAAS-derived agents LV305 and G305.”