CMB305 / Merck (MSD) - LARVOL DELTA

NCI-2018-00926: Modified T Cells, Chemotherapy, and Aldesleukin With or Without LV305 and CMB305 in Treating Participants With Advanced or Recurrent Sarcoma (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed

Metastases • Trial completion • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

A phase 2 study of CMB305 and atezolizumab in NY-ESO-1+ soft tissue sarcoma: Interim analysis of immunogenicity, tumor control and survival (ESMO 2017) - P2; "In the interim analysis, Arm A+C resulted in a higher level of anti-NY-ESO-1 IR when compared to Arm A; pts with IR tend to have better target lesion control. Early data indicate that induction of anti-NY-ESO-1 IR may be associated with better survival."

Clinical • P2 data • Sarcoma

Immune response, safety, and survival impact from CMB305 in NY-ESO-1+ recurrent soft tissue sarcomas (STS). (ASCO 2017) - P1b; "Clinical trial information: NCT02387125 CMB305 is safe, well tolerated, and demonstrates a survival rate that is favorable when compared with approved agents for recurrent STS. CMB305 resulted in a stronger and broader integrated IR than LV305, including antigen spreading. These data warrant further investigation of CMB305 as a monotherapy in a randomized clinical study in STS."

Adverse events • Clinical • Biosimilar • Non Small Cell Lung Cancer • Ovarian Cancer • Pain • Sarcoma

NCI-2018-00926: Modified T Cells, Chemotherapy, and Aldesleukin With or Without LV305 and CMB305 in Treating Participants With Advanced or Recurrent Sarcoma (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial primary completion date • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

Immune response, safety, and overall survival of NY-ESO-1+ soft tissue sarcoma patients treated with CMB305 therapy (ESMO 2018) - P1b; "CMB305 is well tolerated, broadly immunogenic, and impacts patient survival favorably when compared with approved agents for recurrent STS. These results support a randomized phase 3 trial evaluating CMB305 in the maintenance setting after 1st line therapy in SS patients."

Clinical • Sarcoma

A Phase II randomized study of CMB305 and atezolizumab versus atezolizumab in NY-ESO-1+ soft tissue sarcoma: Analysis of immunogenicity, tumor control, and patient survival. (ASCO 2019) - P2; "C consists of a dendritic cell-targeting lentiviral vector encoding NY-ESO-1 gene (LV305), and a TLR-4 agonist NY-ESO-1 recombinant protein plus GLA-SE (G305). Despite no major differences in PFS and OS between the treatment arms (Arm C+A had more advanced disease and more prior lines of chemotherapy), Arm A +C achieved PRs, a higher level of anti-NY-ESO-1 IR, and pts with IR had numerically superior outcomes. Moreover, the clinical benefit of C+A in earlier lines of therapy warrant further study. Clinical trial information: NCT02609984Arm C+A pts with only 1 prior line & SD or better, mOS 24.9 mo (11.0, NR) vs Arm A 17.7 mo (4.6, 26.1)."

Clinical • P2 data • Oncology • Sarcoma • Solid Tumor

Addition of Prime-Boost Vaccination Regimen to Atezolizumab in Soft-Tissue Sarcomas Expressing NY-ESO-1 (THE ASCO POST) - P2, N=89; "The investigators concluded, 'Although the combination of CMB305 and atezolizumab did not result in significant increases in progression-free or overall survival compared with atezolizumab alone, some patients demonstrated evidence of an anti–NY-ESO-1 immune response and appeared to fare better … than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti–PD-L1 therapies merits further evaluation in other clinical contexts.'"

Media quote • P2 data

Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1. (PubMed, J Clin Oncol) - "Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti-programmed death ligand-1 therapies merits further evaluation in other clinical contexts."

Clinical • Journal • P2 data • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • CD8 • CTAG1B • TLR4

Modified T Cells, Chemotherapy, and Aldesleukin With or Without LV305 and CMB305 in Treating Participants With Advanced or Recurrent Sarcoma (clinicaltrials.gov) - P1; N=15; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; Recruiting ➔ Active, not recruiting; Trial completion date: Jun 2021 ➔ Dec 2022; Trial primary completion date: Jun 2021 ➔ Dec 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

A Phase 1b Study Evaluating the Safety, Tolerability, and Immunogenicity of CMB305, a Lentiviral-Based Prime-Boost Vaccine Regimen, in Patients with Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1. (PubMed, Oncoimmunology) - "It is composed of LV305, which is an NY-ESO-1 expressing lentiviral vector, and G305, a recombinant adjuvanted NY-ESO-1 protein...Safety was examined in a 3 + 3 dose-escalation design, followed by an expansion with CMB305 alone or in a combination with either oral metronomic cyclophosphamide or intratumoral injections of a toll-like receptor agonist (glucopyranosyl lipid A)...This is the first trial to test a prime-boost vaccine regimen in patients with advanced cancer. This approach is feasible, can be delivered safely, and with evidence of immune response as well as suggestion of clinical benefit."

Clinical • Journal • P1 data • Fatigue • Hepatology • Liposarcoma • Oncology • Pain • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

CMB305 + atezolizumab: "Interim analysis indicates that addition of CMB305 to atezolizumab may result in clinical efficacy improved over atezolizumab alone in NY-ESO-1+ STS patients with low/absent PD-L1" (Immune Design) - SITC 2017

P2 data • Oncology • Sarcoma

CMB305 + atezolizumab: "Disease Control Rate (Partial Responses (PR) + Stable Disease (SD)): 61%, including 1 PR (C+A) vs. 28% with no PRs (A)" (Immune Design) - ESMO 2017: "Median Progression Free Survival (PFS): 2.6 months (C+A) vs. 1.4 months (A)"

P2 data • Oncology • Sarcoma

Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002) (clinicaltrials.gov) - P2; N=89; Terminated; Sponsor: Immune Design; Completed ➔ Terminated; This study did not meet the efficacy objective

Clinical • Trial termination • Esophageal Squamous Cell Carcinoma • Oncology • Sarcoma • Solid Tumor

CMB305: Anticipated data from P1 monotherapy trial (NCT02387125) in STS at ASCO (June 2-6, 2017)… (Immune Design, Leerink Partners 6th Global Healthcare Conference) - Leerink Partners Global Healthcare Conference 2017: Anticipated data from P1 monotherapy trial (NCT02387125) in STS at ASCO (June 2-6, 2017); Anticipated data from P2 trial (NCT02609984) of CMB305 + atezolizumab in STS at ESMO (September 8-12, 2017)

Anticipated P1 data • Anticipated P2 data • Oncology • Sarcoma

CMB305: Anticipated data from P1 monotherapy trial (NCT02387125) in STS at ASCO (June 2-6, 2017)… (Immune Design, Leerink Partners 6th Global Healthcare Conference) - Leerink Partners Global Healthcare Conference 2017: Anticipated data from P1 monotherapy trial (NCT02387125) in STS at ASCO (June 2-6, 2017); Anticipated data from P2 trial (NCT02609984) of CMB305 + atezolizumab in STS at ESMO (September 8-12, 2017)

Anticipated P1 data • Anticipated P2 data • Oncology • Sarcoma

Immune Design: Corporate Overview (Immune Design) - Anticipated analysis of initial patients in P2 trial (NCT02609984) of CMB305 in combination with atezolizumab for soft tissue sarcoma in Q4 2016; Anticipated data from P1 trial (NCT02387125) for locally advanced, relapsed, or metastatic cancer at ASCO (Jun 2-6, 2017); Anticipated early BLA filing in soft tisue sarcoma in Q4 2018

Anticipated BLA • Anticipated P1 data • Anticipated P2 data • Oncology • Sarcoma

Immune Design: Q3 2015 Results (Immune Design) - Anticipated clinical and immunogenicity data from the first six patients of dose escalation part and from a subset of patients of the expansion part of P1b (NCT02387125) study in metastatic cancer in Q1 2016; Anticipated data from P2 trial of CMB305 in combination atezolizumab in metastatic soft tissue sarcoma in H2 2016

Anticipated P1 data • Anticipated P2 data • Oncology

Immune Design: Corporate Overview (Immune Design) - Anticipated initiation of P2 trial in combination with atezolizumab for soft tissue sarcoma in Q4 2015; Anticipated data on dose escalation from P1 trial (NCT02387125) for solid tumors in YE 2015; Anticipated initial data from signal-seeking expansion arm of P1 trial (NCT02387125) for solid tumors in YE 2015

Anticipated new P2 trial • Anticipated P1 data • Oncology

Immune Design: Corporate Overview (Immune Design) - Anticipated early data from P1 trial (NCT02387125) for ovarian cancer at ASCO (June 3-7, 2016); Anticipated analysis from initial 40 patients of P2 trial (NCT02609984) for soft tissue sarcoma in 2016; Anticipated FDA meeting regarding P2 data of soft tissue sarcoma in 2016; Anticipated complete data from P2 trial (NCT02609984) for soft tissue sarcoma at ASCO (June 2-6, 2017); Anticipated BLA filing for soft tissue sarcoma in 2018

Anticipated FDA event • Anticipated NDA • Anticipated P1 data • Anticipated P2 data • Oncology • Ovarian Cancer • Sarcoma

CMB305 + atezolizumab: Data on >1 year survival from P2 trial (NCT02609984) in STS at ASCO (June 1-5, 2018) (Immune Design) - Corporate Overview: Data on >2 year survival from P2 trial in sarcoma in H1 2019

P2 data • Oncology • Sarcoma

New randomized data from CMB305 + checkpoint inhibitor study demonstrate greater clinical benefit and immune response (GlobeNewswire) - P2, N=88; NCT02609984; "Immune Design...today announced that an interim analysis of...Phase 2 trial showed that NY-ESO-1+ soft tissue sarcoma (STS) patients receiving the combination of CMB305 and...atezolizumab (TECENTRIQ®), experienced greater clinical benefit and immune response than those receiving atezolizumab alone. The data will be presented in a poster discussion session at the European Society of Medical Oncology (ESMO) 2017 Congress..."

P2 data • Oncology • Sarcoma

ID-CMB305: Initiation of pivotal monotherapy trial in STS in H1 2018 (Immune Design) - Corporate Presentation: 18-month survival data from P2 trial (NCT02609984) of CMB305 + atezolizumab in STS in H2 2018

New trial • P2 data • Oncology • Sarcoma

Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1 (clinicaltrials.gov) - P1b; N=79; Terminated; Sponsor: Immune Design; Completed ➔ Terminated; This study did not meet the efficacy objective

Clinical • Trial termination • Gynecologic Cancers • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Reperfusion Injury • Sarcoma • Solid Tumor • Thoracic Cancer

Immune Design reports second quarter 2018 financial results and provides corporate update [CMB305] (GlobeNewswire) - "CMB305: the SYNOVATE Phase 3 trial [NCT03520959] is open for enrollment; combination with atezolizumab Phase 2 ongoing...Immune Design plans to present long-term follow-up data from its CMB305 monotherapy trial in soft tissue sarcoma patients at the European Society for Medical Oncology (ESMO) 2018 Congress in October. The ESMO presentation will be in the forms of both a poster and poster discussion session."

Clinical data • Enrollment open • Oncology • Sarcoma • Solid Tumor

Immune design reports data update for lead immunotherapy programs: improvement in survival for CMB305 monotherapy in sarcoma and increased objective responses for G100/pembrolizumab combination in follicular lymphoma (GlobeNewswire) - P2, N=51; NCT02501473; Sponsor: Immune Design; "Additional responses have been observed in the combination arm (54% ORR, compared to a 15% ORR in the G100+XRT arm)...The patient population with high TLR4 expression in the tumor continue to receive greater benefit, with an updated 75% ORR on the combination arm (6/8 patients)...."

P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor