Immunotherapy developer Immune Design said it will halt a Phase III trial for its lead pipeline candidate, the cancer vaccine CMB305, following disappointing Phase II results in synovial sarcoma, and will instead accelerate and expand development of its next-furthest along candidate, the intratumoral TLR4 agonist G100.

Immune Design said it will “deprioritize” development of CMB305, a prime-boost cancer vaccine designed to target tumors that express the cellular protein NY-ESO-1, which is often frequently expressed in synovial sarcomas.

The company said it will halt the Phase III SYNOVATE trial (NCT03520959), which is designed to assess the cancer vaccine in patients with unresectable, locally-advanced, or metastatic NY-ESO-1 positive synovial sarcoma following first-line systemic anticancer therapy. SYNOVATE had been recruiting patients toward a planned enrollment of 248 participants, as of the study’s most recent update August 24 on

Immune Design cited an early analysis of data from a Phase II study (NCT02609984) that has been assessing the combination of the cancer vaccine and the cancer immunotherapy Tecentriq® (atezolizumab), marketed by Roche and its Genentech subsidiary, in patients with locally advanced, relapsed or metastatic sarcoma (synovial or myxoid/round cell liposarcoma) expressing the NY-ESO-1 protein.

Following the close of trading on the NASDAQ Global Market, Immune Design acknowledged that the Phase II study “showed the combination of CMB305 and Tecentriq (atezolizumab) is not likely to show a survival benefit in relapsed synovial sarcoma patients.”

“Immune Design will seek external collaborations to explore the continued development of CMB305 in sarcoma,” the company added.

Investors responded to the CMB305 Phase III trial halt with a stock selloff that sent the company’s shares tumbling nearly 47% from yesterday’s close of $2.79, to $1.49 as of 9:56 a.m.

CMB305 is administered by injection and is designed to generate an anti-NY-ESO-1 immune response by activating a participant’s antigen-presenting dendritic cells.

G100 is Immune Design’s first product candidate solely generated from the Glucopyranosyl Lipid A Adjuvant Systems (GLAAS) platform. The discovery platform is based on Glucopyranosyl Lipid A (GLA), which is designed to selectively bind to the TLR4 receptor to cause potent activation of dendritic cells. The company says G100 is designed to leverage the range of neoantigens and other endogenous antigens found in the tumor microenvironment to create a systemic antitumor immune response from local injection.

Two Development Goals

According to Immune Design, G100 has a unique mechanism of action that differs from current therapies in lymphoma. It triggers an immune-mediated antitumor effect with a favorable safety profile that the company reasons could position the treatment as a pillar of chemo-free regimens for the treatment of lymphomas and beyond.

Immune Design has articulated two development goals for G100. One is to develop G100 in combination with Merck & Co.’s marketed cancer immunotherapy Keytruda® (pembrolizumab) in follicular lymphoma patients who have received three prior lines of systemic therapy. These patients may represent an unmet medical need, which the company said may allow for an accelerated approval path in that indication.

Immune Design said it plans to evaluate the clinical activity of the G100/Keytruda combination based on Objective Response Rate (ORR) in an open-label setting. To accelerate enrollment, the company said it plans to use both an open IND and submit a new IND for this specific unmet medical need population, as requested by the FDA. Data from both INDs would be combined in a potential BLA filing.

Based on existing ORR data, Immune Design has estimated that approximately 100 patients may be required—though the sample size will depend on the ORR observed in the initial set of patients.

The second development goal for G100, Immune Design said, will be to assess the treatment beyond late-stage follicular lymphoma, including:

  • In earlier-stage follicular lymphoma patients in combination with the Genentech (Roche)/Biogen co-marketed Rituxan® (rituximab).
  • In combination with unspecified other agents in both indolent and aggressive lymphomas that are known to express TLR4.
  • In solid tumors, initially through supporting investigator-sponsored studies.

Immune Design said the ramp-up of G100 and wind-down of CMB305, and “an associated company restructuring” on which the company offered no details, will extend its cash runway into 2021. As of June 30, the company reported $73.430 million in cash and cash equivalents, up 1% from $72.454 million as of December 31, 2017.

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