10 th EADO Congress Vilnius, 7-10 May 2014 Ipilimumab update Michele Maio Medical Oncology and Immunotherapy, Department of Oncology University Hospital of Siena, Istituto Toscano Tumori SIENA, ITALY
Evolving Therapeutic Options for Cancer Treatment Surgery Chemotherapy Radiotherapy
Evolving Therapeutic Options for Cancer Treatment Surgery Chemotherapy Radiotherapy Immunotherapy
Science, 2013 Science 2013
D E C E M B E R 2 0 1 1 VO L 4 8 0 N AT U R E 4 8 1 T-cell costimulatory receptors
Melanoma as a tool for cancer Tissue samples readily accessible Adaptable to tissue culture Amenable to testing of novel therapies research
Immunotherapy in solid tumors with immunomodulating antibodies Brain Mesothelioma Lung cancer (NSCLC, SCLC) Melanoma Breast cancer Renal cancer Gastroesophageal cancer Prostate cancer Bladder cancer Pancreatic cancer Colorectal cancer
Chemotherapy/Targeted Agents and Immuno-therapy Differ in Action and Outcome Response Chemotherapy and Targeted Therapies IMMUNOTHERAPY 0 6 12 Time (months) Maio M. et al, unpublished
Overall survival rates EAP 10 mgs Time 1-year 2-year 3-year 4-year OS 34.8 23.5 20.9 20.9* SE% (9.6) (8.4) (8.0) (8.0) *Di Giacomo AM, et al. Cancer Immunol. Immunother. 2013
Survival Analysis with 5 Years of Follow-up in a Phase III Study of Ipilimumab and Dacarbazine in Metastatic Melanoma Michele Maio, 1 Igor Bondarenko, 2 Caroline Robert, 3 Luc Thomas, 4 Claus Garbe, 5 AlessandroTestori, 6 Haolan Lu, 7 Kevin Chin, 7 Jedd D. Wolchok 8 1 University Hospital of Siena, Siena, Italy; 2 Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; 3 Institute Gustave Roussy, Villejuif, France; 4 Lyon 1 University, Centre Hospitalier Lyon Sud Pierre Bénite France; 5 University Medical Center, Tuebingen, Germany; 6 Istituto Europeo di Oncologia, Milan, Italy; 7 Bristol-Myers Squibb, Wallingford, CT, USA; 8 Memorial Sloan-Kettering Cancer Center, New York, NY, USA Abstract Number 3704
Kaplan-Meier Plot of Overall Survival Proportion Alive 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Patients at Risk DTIC + Ipi DTIC + Placebo 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 Months DTIC + 10 mg/kg Ipi Censored DTIC + Placebo Censored 250 200 159 116 92 80 69 60 57 50 47 46 44 43 42 40 17 6 0 0 252 192 136 90 73 56 44 42 34 30 26 24 23 21 21 20 9 4 1 0 CONFIDENTIAL. Not for further distribution. Maio M, ESMO 2013
Pooled Analysis of Long-term Survival Data From Phase II and Phase III Trials of Ipilimumab in Metastatic or Locally Advanced, Unresectable Melanoma Schadendorf D, 1 Hodi FS, 2 Robert C, 3 Weber JS, 4 Margolin K, 5 Hamid O, 6 Chen TT, 7 Berman DM, 8 Wolchok JD 9 1 University Hospital Essen, Essen, Germany; 2 Dana-Farber Cancer Institute, Boston, MA, USA; 3 Institute Gustave Roussy, Villejuif, France; 4 Moffitt Cancer Center, Tampa, FL, USA; 5 University of Washington, Seattle, WA, USA; 6 The Angeles Clinic and Research Institute, Los Angeles, CA, USA; 7 Bristol-Myers Squibb, Wallingford, CT, USA; 8 Bristol-Myers Squibb, Lawrenceville, NJ, USA; 9 Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Abstract Number 24LBA
Studies Included in OS Analyses* Study ID Phase N Population Dose Retreatment or Maintenance MDX010-20 3 540 Previously treated 3 mg/kg ± gp100 Retreatment CA184-024 3 250 Treatment-naive 10 mg/kg + DTIC Maintenance CA184-022 2 217 Previously treated 0.3, 3, 10 mg/kg Maintenance CA184-008 2 155 Previously treated 10 mg/kg Maintenance CA184-007 2 115 CA184-004 2 82 CA184-042 2 72 Treatment-naive or previously treated Treatment-naive or previously treated Melanoma with brain metastases NCI04C0083 1/2 88 Previously treated NCI02C0106 1/2 56 Previously treated NCI03C0109 1/2 36 Previously treated 10 mg/kg ± budesonide Maintenance 3, 10 mg/kg Maintenance 10 mg/kg Maintenance 3, 5, 9 mg/kg ± gp100 3 mg/kg + gp100 3 1 mg/kg + gp100 0.1, 0.3, 1, 2, 3 mg/kg + IL-2 Not included Not included Not included CA184-338 Observational 160 Treatment-naive 3 mg/kg No (induction only) CA184-332 Observational 90 Treatment-naive 3 mg/kg No (induction only) Expanded Access CA184-045** 2985 Previously treated 3, 10 mg/kg Maintenance for 10 mg/kg Program (EAP) *Total of 1861 patients for primary analysis; N=4846 patients including EAP. **US EAP treatment protocol. Hodi S, ESMO 2013
Primary Analysis of Pooled OS Data: 1861 Patients 1.0 0.9 0.8 Median OS, months (95% CI): 11.4 (10.7 12.1) Proportion Alive 0.7 0.6 0.5 0.4 0.3 3-year OS rate, % (95% CI): 22 (20 24) 0.2 0.1 0.0 Ipilimumab CENSORED Patients at Risk 0 12 24 36 48 60 72 84 96 108 120 Months Ipilimumab 1861 839 370 254 192 170 120 26 15 5 0 Hodi S, ESMO 2013
Pooled OS Analysis Including EAP Data: 4846 Patients 1.0 Proportion Alive 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 Median OS, months (95% CI): 9.5 (9.0 10.0) 3-year OS rate, % (95% CI): 21 (20 22) 0.1 0.0 Ipilimumab CENSORED 0 12 24 36 48 60 72 84 96 108 120 Months Patients at Risk Ipilimumab 4846 1786 612 392 200 170 120 26 15 5 0 Hodi S, ESMO 2013
The European Ipilimumab Expanded Access Programme: Efficacy and Safety Data from the Italian Cohort of Patients with Pretreated Advanced Melanoma Maio et al. European Ipilimumab EAP, Italian Cohort of Patients.
OS for BRAF-mutation Positive (n=173) and BRAF Wild-Type (n=296) Patients AScierto PA et al, Cancer Invest. 2014
Elderly Patients (>70 years): OS Chiarion-Sileni V et al, J Exp Clin Cancer Res. 2014
Survival analysis in MM pts treated with IPI 10mg according to the circulating CD4+ICOS+ (w7) median OS = 118 wks log-rank test, p = 0.009 median OS = 27 wks Di Giacomo AM, et al. Cancer Immunol. Immunother. 2013 CD4+ICOS+ > 4 fold increase CD4+ICOS+ 4 fold increase
Can melanoma continue to serve as a model tumour for immunotherapy? To investigate Adjuvant treatment Might immunotherapies be more effective if used when disease burden is lower and the immune system less compromised by the tumour? Combination/Sequencing therapies Biomarker development (surrogate/predictive) 21
Therapeutic combinations Chemotherapy Surgery Immunotherapy Radiotherapy Target Melero I. et al Nat rev cancer (2007) modified