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Results 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
Annals of Oncology 25 (Supplement 4): iv374–iv393, 2014 doi:10.1093/annonc/mdu344.18
melanoma and other skin tumours 1102P
abstracts
J.J. Nemunaitis1, R.H. Andtbacka2, M. Ross3, T. Amatruda4, J. Chesney5, F. A. Collichio6, K.J. Harrington7, N.M. Steven8, S. Fourie9, L. Dreosti10, A. Li11, K. Liu11, M. Shilkrut12, R. Coffin13, H. Kaufman14 1 Medical Oncology, Mary Crowley Cancer Research Center, Dallas, TX, USA 2 Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA 3 Surgical Melanoma, MD Anderson Cancer Center, Houston, TX, USA 4 Oncology, Hubert H. Humphrey Cancer Center, Robbinsdale, MN, USA 5 Medical Oncology/hematology, University of Louisville, Louisville, KY, USA 6 Division of Hematology and Oncology, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA 7 Cancer Biology and Radiotherapy and Imaging, Institute of Cancer Research/The Royal Marsden Hospital, London, UK 8 Medical Oncology, Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital Queen Elizabeth Medical Centre, Birmingham, UK 9 Radiation Oncology, Wilgers Oncology Centre, Pretoria, SOUTH AFRICA 10 Medical Oncology, University of Pretoria, Pretoria, SOUTH AFRICA 11 Biostatistics, Amgen Inc., Thousand Oaks, CA, USA 12 Clinical Oncology, Amgen Inc., Thousand Oaks, CA, USA 13 Clinical Oncology, Amgen Inc., Woburn, MA, USA 14 Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
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 < 0.0001) in patients ( pts) with stage IIIB-IV melanoma (Andtbacka et al,
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv382/2241805 by guest on 24 October 2019
RESULTS 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
ASCO 2013). Here we report the results of an extension trial of OPTiM as of Mar 2013. 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 <6 m). A tolerable safety profile consistent with that seen in the main OPTiM study was observed. 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.
melanoma and other skin tumours 1102P
abstracts
J.J. Nemunaitis1, R.H. Andtbacka2, M. Ross3, T. Amatruda4, J. Chesney5, F. A. Collichio6, K.J. Harrington7, N.M. Steven8, S. Fourie9, L. Dreosti10, A. Li11, K. Liu11, M. Shilkrut12, R. Coffin13, H. Kaufman14 1 Medical Oncology, Mary Crowley Cancer Research Center, Dallas, TX, USA 2 Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA 3 Surgical Melanoma, MD Anderson Cancer Center, Houston, TX, USA 4 Oncology, Hubert H. Humphrey Cancer Center, Robbinsdale, MN, USA 5 Medical Oncology/hematology, University of Louisville, Louisville, KY, USA 6 Division of Hematology and Oncology, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA 7 Cancer Biology and Radiotherapy and Imaging, Institute of Cancer Research/The Royal Marsden Hospital, London, UK 8 Medical Oncology, Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital Queen Elizabeth Medical Centre, Birmingham, UK 9 Radiation Oncology, Wilgers Oncology Centre, Pretoria, SOUTH AFRICA 10 Medical Oncology, University of Pretoria, Pretoria, SOUTH AFRICA 11 Biostatistics, Amgen Inc., Thousand Oaks, CA, USA 12 Clinical Oncology, Amgen Inc., Thousand Oaks, CA, USA 13 Clinical Oncology, Amgen Inc., Woburn, MA, USA 14 Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
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 < 0.0001) in patients ( pts) with stage IIIB-IV melanoma (Andtbacka et al,
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv382/2241805 by guest on 24 October 2019
RESULTS 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
ASCO 2013). Here we report the results of an extension trial of OPTiM as of Mar 2013. 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 <6 m). A tolerable safety profile consistent with that seen in the main OPTiM study was observed. 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.