Clinical Trials

Date: 2018-03-12

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: Immune Design (USA - MA)

Product: CMB305 (LV305 and G305) - dendritic-cell targeting, lentiviral vector encoding the NY-ESO-1 gene05

Action mechanism:

• immunotherapy product/cell therapy/gene therapy. CMB305 is a cancer immunotherapy product candidate that involves the sequential dosing of LV305 and G305. LV305 is a hybrid vector from the 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 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 the 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.

Disease: soft tissue sarcoma

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On October 11, 2018, Immune Design announced program updates CMB305 cancer vaccine program in development for the treatment of cancer. Based on a recent review of the CMB305 program, including an early analysis of the ongoing Phase 2 study that showed the combination of CMB305 and Tecentriq® (atezolizumab) is not likely to show a survival benefit in relapsed synovial sarcoma patients, the company has decided to discontinue the SYNOVATE trial. Immune Design will seek external collaborations to explore the continued development of CMB305 in sarcoma.
• • On March 12, 2018, Immune Design announced updated data from trials evaluating its lead product candidate, CMB305.
• Data Update from the CMB305 Monotherapy Trial: Immune Design initially presented data at the American Society of Clinical Oncology 2017 Annual Meeting from 25 NY-ESO-1⁺ soft tissue (STS) patients, including 14 synovial sarcoma patients. The median follow up at the time was 11.4 months, in a patient population where 92% had relapsed or refractory metastatic disease, 52% had received ?2 lines of chemotherapy, and 56% had actively progressing disease at study entry, an unfavorable prognostic factor.
• As of the time of the most recent data analysis, median follow up of patients was 17.7 months.  Observations are as follows:
• • Median overall survival (OS) across all STS patients has been reached at 23.7 months. The median OS for the subset of synovial sarcoma patients, the targeted patient population in the company’s planned Phase 3 trial, has still not yet been reached.
  • These survival data compare favorably to the reported median OS for approved second line and later agents, which are only 12.4-13.5 months for STS patients, and 11.7 months for synovial sarcoma patients specifically.

  • Patients who develop an anti-NY-ESO-1 immune response on CMB305 therapy have better survival. • CMB305 continues to be well tolerated, with only one Grade 3 adverse event. • On June 5, 2017, Immune Design announced updated clinical and biomarker data for its lead immuno-oncology product candidate CMB305  at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting in Chicago.
• CMB305 Monotherapy in Soft Tissue Sarcoma Patients: Clinical Benefit, Safety and Patient Selection
• Data in an oral presentation by Neeta Somaiah, M.D., Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, highlight the results of 25 soft tissue sarcoma (STS) patients with recurrent disease treated with CMB305:
• Patient characteristics: 92% metastatic, 56% progressing upon trial entry, and 52% with ?2 prior lines of chemotherapy
• Survival: median overall survival (mOS) has still not yet been reached.
• The overall survival rate at 12 and 18 months was 83% and 76%, respectively.
• • These new data compare favorably to mOS for approved second line and later sarcoma agents, which is only 12.4-13.5 months, as well as a published mOS of 11.7 months for synovial sarcoma patients specifically; the largest patient population enrolled in this trial.
• Disease control: a disease control rate (CDR) of 64% (16/25) was observed, including durable tumor growth arrest in patients who had evidence of disease progression at study entry.
• Safety: CMB305 was well tolerated, with only one related Grade 3 adverse event (AE).
• Immune response: CMB305 generated a strong and broad anti-NY-ESO-1 immune response in >50% of the patients, with 32% patients experiencing an integrated response (T cells and antibodies).
• Antigen spreading: induction of an immune response against other tumor antigens not targeted by CMB305 was detected in 33% of evaluable patients following CMB305 therapy.

Is general: Yes