JAVELIN Solid Tumor Trial: Avelumab in Locally Advanced or Metastatic Breast Cancer CCO Independent Conference Coverage*: The 2015 Annual Meeting of the CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2015 San Antonio, Texas *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from Genentech and Novartis.

JAVELIN: Background Avelumab (formerly MSB0010718C) Investigational anti–PD-L1 IgG1 monoclonal antibody Binds to PD-L1, blocking interaction with PD-1 receptors[1] PK, preliminary safety data support dosing up to 20 mg/kg every 2 wks[2] Demonstrated activity against solid tumors in pts unselected for PD-L1 expression, including NSCLC, ovarian cancer, gastric cancer, urothelial carcinoma[3-6] This analysis reporting on phase Ib JAVELIN study MBC cohort[7] MBC, metastatic breast cancer; NSCLC, non-small-cell lung cancer. 1. Heery CR, et al. ASCO 2014. Abstract 3064. 2. Heery CR, et al. ASCO 2015. Abstract 3055. 3. Gulley JL, et al. ASCO 2015. Abstract 8034. 4. Disis ML, et al. ASCO 2015. Abstract 5509. 5. Chung, HC, et al. ECC 2015. Abstract 2364. 6. Apolo AB, et al. ECC 2015. Abstract 2630. 7. Dirix LY, et al. SABCS 2015. Abstract S1-04. Slide credit: clinicaloptions.com

JAVELIN: Phase Ib Study Design Pts with refractory or progressive locally advanced or MBC (N = 168)* Avelumab 10 mg/kg IV Q2W Dosing until progression Primary endpoint: DLT Secondary endpoints: clinical activity, immune response, safety PD-L1 expression assessed by IHC DLT, dose-limiting toxicity; ECOG, Eastern Cooperative Oncology Group; MBC, metastatic breast cancer; PS, performance status. *Pts eligible if ≤ 3 previous cytotoxic regimens, previous treatment with taxane + anthracycline, biopsy/tissue sample taken within 90 days of avelumab initial dose, ECOG PS 1 or 2, ≥ 1 quantifiable lesion, life expectancy ≥ 3 mos. Pts unselected for PD-L1 expression, HER2/ER/PR subtype. Slide credit: clinicaloptions.com Dirix LY, et al. SABCS 2015. Abstract S1-04.

JAVELIN: Baseline Characteristics All Pts (N = 168) Pts With TNBC (n = 58) Median age, yrs (range) 55 (31-81) 52.5 (31-80) Female, % 99.4 100 ECOG PS, % 1 49.4 50.6 56.9 43.1 Molecular subtype, % TNBC HER2-/ER+ or HER2-/PgR+ HER2+ Unknown 34.5 42.9 15.5 7.1 -- Previous regimens,* % ≥ 3 2 ≤ 1 52.4 20.8 26.8 22.4 27.6 50.0 Median time since Dx of MBC, mos (range)† 21.6 (0.7-176.8) 13.2 (0.7-176.8) Dx, diagnosis; ECOG PS, Eastern Cooperative Oncology Group performance status; MBC, metastatic breast cancer; TNBC, triple-negative breast cancer. *Excluding neoadjuvants. †Missing data in 8 pts. Slide credit: clinicaloptions.com Dirix LY, et al. SABCS 2015. Abstract S1-04.

JAVELIN: Antitumor Activity Best Overall Response, % All Pts (N = 168) Pts With TNBC (n = 58) CR 0.6 PR 4.2 8.6 SD* 23.2 22.4 PD 63.1 65.5 Not evaluable 8.9 3.4 ORR 4.8 (95% CI: 2.1-9.2) 8.6 (95% CI: 2.9-19.0) DCR† 28.0 31.0 DCR, disease control response; PD, progressive disease; SD, stable disease; TNBC, triple-negative breast cancer. *Defined as SD at first assessment after 6 wks. †Defined as response plus SD. Slide credit: clinicaloptions.com Dirix LY, et al. SABCS 2015. Abstract S1-04.

JAVELIN: ORR According to PD-L1 Expression ORR increased in pts with PD-L1–positive tumors Pts with PD-L1 expression by immune cells showed greater response than pts with PD-L1–negative immune cells (33.3% [4/12] vs 2.4% [3/124]) PD-L1 expression also appeared associated with ORR in subgroup with TNBC (4 of 9 PD-L1 positive vs 1/39 PD-L1 negative) TNBC, triple-negative breast cancer. Slide credit: clinicaloptions.com Dirix LY, et al. SABCS 2015. Abstract S1-04.

JAVELIN: Treatment-Emergent AEs Patients With TEAEs, % Most Common TEAEs All Grades* (n = 168) TEAEs, Grade ≥ 3† Any treatment-related event 68.5 13.7 Fatigue 19.0 1.8 Infusion-related reactions 14.3 Nausea 13.1 Diarrhea 8.9 Arthralgia 7.7 0.6 Decreased appetite 7.1 Influenza-like illness 6.5 GGT increase 2.4 Autoimmune hepatitis Anemia AE, adverse event; GGT, gamma-glutamyl transferase; TEAE, treatment-emergent adverse event. *Occurring in > 5%. †Occurring in > 1%. Slide credit: clinicaloptions.com Dirix LY, et al. SABCS 2015. Abstract S1-04.

JAVELIN: Potential Autoimmune TEAEs Treatment-related discontinuation occurred in 8 pts (4.8%) Death in 2 pts considered treatment related (1.2%) Acute liver failure (autoimmune hepatitis in pt w/ liver metastasis) Respiratory distress (prior/ongoing history respiratory disorders) Pts, % TEAEs, % (N = 168) Grade (n) Pts with any event 10.1 1/2 (13); 3/4 (4) Hypothyroidism 4.8 1/2 (8) Autoimmune hepatitis 1.8 3 (3) Pneumonitis 1/2 (2); 3 (1) Thrombocytopenia 1.2 1 (1); 4 (1) TEAE, treatment-emergent adverse event. Slide credit: clinicaloptions.com Dirix LY, et al. SABCS 2015. Abstract S1-04.

JAVELIN: Conclusions Avelumab had an acceptable safety in pts with locally advanced or metastatic breast cancer ORR in overall population: 4.8% (95% CI: 2.1-9.2) Higher rate in pts with TNBC: 8.6% (95% CI: 2.9-19.0) ORR increased in pts with PD-L1–positive tumors (33.3% [4/12] vs 2.4% in PD-L1- tumors [3/124]) PD-L1 expression also appeared associated with ORR in subgroup with TNBC (PD-L1 positive 44.4% [4/9] vs PD-L1 negative 2.6% [1/39]) Evaluation of avelumab in metastatic breast cancer ongoing ORR, overall response rate; TNBC, triple-negative breast cancer. Slide credit: clinicaloptions.com Dirix LY, et al. SABCS 2015. Abstract S1-04.

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