Mark Shilkrut

Final planned overall survival (OS) from OPTiM, a randomized Phase III trial of talimogene laherparepvec (T-VEC) versus GM-CSF for the treatment of unresected stage IIIB/C/IV melanoma (NCT00769704)

Meeting abstracts T-VEC is an oncolytic immunotherapy derived from herpes simplex virus type-1 designed to selectively replicate within tumors and to produce GM-CSF to enhance systemic antitumor immune responses. OPTiM, a randomized Phase III trial of T-VEC vs GM-CSF in patients with unresected

Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma

Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).

1102PRESULTS OF THE EXTENSION TRIAL OF OPTIM, A MULTICENTER, RANDOMIZED PHASE 3 TRIAL OF TALIMOGENE LAHERPAREPVEC (T-VEC) VS GM-CSF FOR UNRESECTED STAGE IIIB-IV MELANOMA

ABSTRACT Aim: T-VEC is an HSV-1-derived oncolytic immunotherapy designed to selectively replicate in tumors and produce GM-CSF to enhance systemic antitumor immune responses. Compared to GM-CSF alone, T-VEC significantly improved durable response rate (DRR; partial response [PR] or complete response [CR] lasting continuously for ≥ 6 months [m]) from 2% to 16% (p Methods: Pts were eligible for the extension trial if: 1) they had received the maximum treatment (tx) cycles allowed on OPTiM and did not have disease progression (PD) associated with reduced performance status or 2) had a CR on OPTiM and then developed new lesions within 12 m. In the extension study, pts could continue their randomized tx: T-VEC (intralesional ≤ 4 mL × 108 pfu/mL q2w) or GM-CSF (sc 125 µg/m2 qd × 14 days q4w) until CR, additional 12 m of tx, PD or unacceptable toxicity. The primary endpoint was safety; efficacy was also evaluated. Results: 30 (27 T-VEC, 3 GM-CSF) of the 436 pts enrolled in OPTiM entered the extension trial. Including OPTiM tx, median duration of tx was 91 wks (range: 29-132) for T-VEC and 100 wks (54-120) for GM-CSF. Most common adverse events (AE) on each arm were chills and pyrexia. There were no grade 5 tx-related AEs. For T-VEC, 5 new CR occurred (best OPTiM response was 3 PR and 2 stable disease [SD]). Best overall response was maintained in 16 pts (1 CR, 6 PR, and 9 SD), 2 pts progressed from PR to SD; PD occurred in 4 pts. A new DR occurred in 1 T-VEC- treated pt. For GM-CSF, PR was maintained in 1 pt and 2 pts progressed from PR to SD. For both trials combined, CR, OR, and DR rates per investigator for T-VEC were 16.3%, 31.5%, and 19.3%, respectively, and 0.7%, 6.4%, and 1.4% for GM-CSF. Conclusions: Continued tx with T-VEC but not GM-CSF was associated with improved response rates, with 5 additional CR and one DR (ie. previously a response of Disclosure: R.H. Andtbacka: RHIA has participated in advisory boards for Amgen Inc.; T. Amatruda: TA has been a site principal investigator for trials funded by Amgen Inc. He has no financial conflicts of interest; J. Chesney: JC has participated in an advisory board for Amgen Inc.; F.A. Collichio: FC has been a consultant to Amgen and received research support from Bristol-Myers Squib, GSK, Morphotek and Amgen, all paid to her institution. (University of North Carolina). (per OPTIM MS disclosure); A. Li: AL is an employee of and shareholder in Amgen Inc.; K. Liu: KL is an employee of and shareholder in Amgen Inc.; M. Shilkrut: MS is an employee of and shareholder in Amgen Inc.; R. Coffin: RC has been a consultant to Amgen Inc. and is a shareholder in Amgen Inc.; H. Kaufman: HK has received honoraria from Amgen Inc. for participating in advisory boards and research funding to conduct clinical trials. All other authors have declared no conflicts of interest.

Abstract B13: A phase 2, randomized, open-label trial assessing efficacy and safety of talimogene laherparepvec (T-VEC) neoadjuvant treatment (tx) plus surgery vs. surgery for resectable stage IIIB-IVM1a melanoma

Background: The risk of recurrence and death in patients (pts) with stages IIIB to IVM1a melanoma following resection is high. T-VEC is an HSV-1 derived oncolytic immunotherapy designed to selectively replicate in tumors and produce GM-CSF to enhance systemic antitumor immune responses. In OPTiM, a randomized phase 3 trial of intralesional T-VEC vs subcutaneous GM-CSF in pts with unresected Stage IIIB-IV melanoma, intralesional T-VEC improved durable response rate (DRR; partial response or complete response [CR] lasting continuously for ≥6 months [m]) from 2% to 16% (P Methods: This is a phase 2, multicenter, randomized, open-label study designed to estimate the efficacy of neoadjuvant T-VEC followed by surgery compared to surgery alone in pts with resectable stage IIIB, IIIC, or IVM1a melanoma. Key eligibility criteria are age ≥ 18 y old, melanoma stages IIIB/C or IVM1a with at least 1 injectable lesion, and Eastern Cooperative Oncology Group performance status 0 or 1. Prior systemic, regional, and radiation therapies for melanoma must have been completed ≥ 3 m prior to randomization. Primary ocular and mucosal melanoma is excluded. Pts with history or evidence of symptomatic autoimmune disease, immunodeficiency, clinically significant immunosuppression, active herpetic skin lesions or prior complications of HSV-1 infection, intermittent/chronic systemic tx with an antiherpetic drugs, and prior T-VEC or tumor vaccines are excluded. 150 pts are planned to be randomized 1:1 to receive either (A) 6 doses of T-VEC for 12 w followed by resection or (B) immediate resection. T-VEC will be administered intralesionally into injectable cutaneous, subcutaneous, and nodal tumors initially at a dose of 106 plaque forming units (PFU)/mL at d1 w1 followed by 108 PFU/mL at d1 of w4, 6, 8, 10, and 12, or until all injectable tumors have disappeared or intolerance to T-VEC, whichever is first. Pts experiencing growth in existing tumors or the appearance of new tumors can remain on T-VEC until w12 of therapy unless other tx, including immediate surgery, is warranted per investigator. The primary endpoint is recurrence-free survival (RFS). The primary analysis of the RFS will occur at the later timepoint of either 2 y after the end of randomization or 64 events of recurrence based on assumption of HR 0.6 benefiting T-VEC arm in RFS at 2 y. Additional and the final analyses will occur at 3 and 5 y after the randomization. Secondary endpoints are 2-y, 3-y, 5-y RFS, OS, overall tumor response and tumor response in injected and uninjected lesions (T-VEC arm only), rates of R0 resection and pathological CR, local recurrence and distant metastases-free survival, and safety. Tumors and blood samples will be collected before and after T-VEC tx to investigate the relationship between biomarkers of the immune system and response to tx. Citation Format: Robert HI Andtbacka, Mohamed Shabooti, Ai Li, Michael Chastain, Mark Shilkrut. A phase 2, randomized, open-label trial assessing efficacy and safety of talimogene laherparepvec (T-VEC) neoadjuvant treatment (tx) plus surgery vs. surgery for resectable stage IIIB-IVM1a melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B13.

Use Patterns and Costs of Isolated Limb Perfusion and Infusion in the Treatment of Regionally Metastatic Melanoma: A Retrospective Database Analysis

Aim: Isolated limb perfusion and infusion (ILP/ILI) are therapies for regionally metastatic melanoma where high doses of anticancer drugs are delivered directly into the circulation of an affected limb, while minimizing systemic drug exposure. This procedure can lead to high response rates but without proven benefits to overall survival. It is recommended by ESMO and NCCN guidelines as a treatment option for patients with stage III unresectable metastatic melanoma. However, limited information is available on its use pattern and costs in the literature. This study was to examine patterns of ILP/ILI use and associated costs in patients with melanoma in the US. Methods: This is a retrospective, observational study using large administrative claims from the MarketScan® databases. Patients who underwent ILP/ILI (CPT-4: 36823) with diagnosis of melanoma (ICD-9-CM: 172.xx, V10.82) between 1/1/2002 and 3/31/2013 were included. Patient characteristics, use patterns, hospital length of stay, and costs (2013 US

Association between durable response (DR) and overall survival (OS) in patients with unresected stage IIIb-IV melanoma treated with Talimogene Laherparepvec (T-VEC) in the Phase III OPTiM trial

) of ILP/ILI were assessed.

1118PUSE PATTERNS AND COSTS OF ISOLATED LIMB PERFUSION AND INFUSION IN THE TREATMENT OF REGIONALLY METASTATIC MELANOMA: A RETROSPECTIVE DATABASE ANALYSIS

Meeting abstracts T-VEC is an HSV-1-derived oncolytic immunotherapy designed to selectively replicate within tumors, produce GM-CSF and enhance systemic antitumor immune responses. In OPTiM ([NCT00769704][1]), a randomized Phase III trial of intralesional T-VEC vs subcutaneous GM-CSF for unresected

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial

Introduction Isolated limb perfusion and infusion (ILP/ILI) are therapies for regional metastatic melanoma that allow high doses of anticancer drugs to be delivered directly into the circulation of an affected limb, thereby minimizing systemic drug toxicity. This procedure can lead to high response rates and is recommended in patients with Stage III unresectable metastatic melanoma. However, limited information is available on patterns of use and costs. This study examined patterns of ILP/ILI use and associated costs in patients with melanoma in the United States (US).