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

CMB305: FDA feedback related to pivotal path by Q4 2017 (Immune Design) - Corporate Overview: Initiation of pivotal monotherapy trial in STS in 2018; 1-year data from pivotal monotherapy trial in STS in H1 2019

Clinical data • FDA event • New trial • Oncology • Sarcoma • Solid Tumor

Study of Adoptive Immunotherapy Using Autologous CD8+ NY-ESO-1-Specific T Cells and the NY-ESO-1 Immunostimulatory Agents LV305 or CMB305 For Patients With Sarcoma (clinicaltrials.gov) - P1; N=18; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center

New P1 trial • Biosimilar • Cardiovascular • Oncology • Reperfusion Injury • Sarcoma • Solid Tumor