Immune Design’s Immunotherapy Candidates Show Promise in Early Clinical Trials

Immune Design’s Immunotherapy Candidates Show Promise in Early Clinical Trials

Updated clinical trial data of Immune Design’s two lead immunotherapy candidates indicate the treatments hold promise to become new additions to the portfolio of immune-targeting compounds available to oncologists.

Researchers from several leading cancer institutions presented the data recently at American Society of Clinical Oncology (ASCO) 2017 Annual Meeting in Chicago.

“These data demonstrate that both CMB305 and G100, our lead cancer immunotherapy product candidates, are capable of activating patients’ immune systems in ways that have a direct effect on patients’ tumor growth, whether it is tumor-growth arrest on CMB305 therapy and subsequent survival benefit, or ORR and systemic tumor shrinkage after local therapy with G100,” Sergey Yurasov, MD, PhD, senior vice president and chief medical officer at Immune Design, said in a press release.

The company’s candidates were featured in three presentations, two of which dealt with CMB305.

Neeta Somaiah, MD, from the University of Texas MD Anderson Cancer Center, presented data from a Phase 1 clinical trial in sarcoma (NCT02387125).

The study, “Immune response, safety, and survival impact from CMB305 in NY-ESO-1+ recurrent soft tissue sarcomas (STS),” described data from 25 patients with soft tissue sarcoma with recurrent disease.

Most patients in the study had seen their cancer spreading; 92 percent had metastases. More than half of the group, 56 percent, was progressing when enrolled in the trial, and 52 percent had gone through two or more lines of chemotherapy.

Despite their advanced disease, the median overall survival of this CMB305-treated group still has not yet been reached. Overall survival at 12 months was 83 percent, and dropped to 76 percent six months later.

Compared to approved second and later line sarcoma treatments, these figures speak to the benefits CMB305. Median overall survival with other treatments is in the range of 12.4-13.5 months. The previously published median overall survival in people with synovial sarcoma — making up the largest group enrolled in the trial — is 11.7 months, researchers underscored.

The study also showed that CMB305 was linked to a disease control rate of 64 percent, including halted tumor growth in patients with progressing disease at study start.

Importantly, the treatment was well-tolerated, with only one grade 3 adverse event that could be related to the treatment.

CMB305 is a compound targeting a molecule called NY-ESO-1. In more than half the group, the drug triggered a strong immune response toward the molecule. In nearly one-third of patients, the immune response involved actions of both T-cells and antibodies.

In addition, researchers noted that the treatment triggered immune responses directed at other tumor factors not directly targeted by CMB305, in one-third of patients.

In another presentation, “Association of CMB305 or LV305-induced and baseline anti-NY-ESO-1 immunity with survival in recurrent cancer patients,” Seth M. Pollack, MD, of the Fred Hutchinson Cancer Research Institute, highlighted data of the relationship between immune response against NY-ESO-1 and clinical benefits in 64 patients with various tumors, treated with CMB305 and LV305 in two ongoing Phase 1 trials (NCT02387125 and NCT02609984).

LV305 is a component of CMB305, and was explored in a separate Phase 1 trial.

The data show that about half of included patients had a low level of anti-NY-ESO-1 immunity before the treatment. This immunity seemed to be expanded by CMB305 treatment.

Findings suggested that biomarker measures of the immune response associated with  the treatment was linked to better patient survival, particularly among those who had pre-existing anti-NY-ESO-1 immunity.

The insights might aid in selecting patients likely to respond to CMB305 treatment for future trials.

The last presentation — “Intratumoral G100 to induce systemic immune responses and abscopal tumor regression in patients with follicular lymphoma,” — given by Christopher Flowers, MD, from the Emory University School of Medicine, focused on G100 treatment effects.

The Phase 1/2 study (NCT02501473) involved nine patients with follicular lymphoma. The group was composed of those who had received previous treatments, as well as treatment-naïve patients. Most had stage 3 or 4 disease, and 78 percent were progressing when they enrolled in the trial.

Researchers reported that 44 percent of patients, receiving three different doses, had a treatment response, defined as at least 50 percent tumor reduction. Some patients saw their tumors continuously shrink for more than eight months, while others had responses for more than four months.

All patients, however, achieved at least stable disease status. Importantly, about half the group experienced that tumors at locations not receiving the localized treatment also shrank, a phenomenon researchers call abscopal tumor regression. Analyses showed that the immune response also was active at tumor sites distant from the treated area.

Patients experienced only mild adverse events that could be linked to the treatment.

“We plan to present these clinical data to regulatory agencies in planning for a pivotal trial that may lead to subsequent regulatory approval, and enable us to bring these novel, safe immunotherapies to cancer patients,” said Yurasov.

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