Outcomes of Patients Who Progressed on Avelumab + Axitinib

BACKGROUND METHODS

Outcomes of patients who progressed • RCC is the most common kidney cancer and constitutes • In the phase 3 JAVELIN Renal 101 trial, A + Ax demonstrated • In the JAVELIN Renal 101 trial, treatment-naive patients • Patients receiving 2L systemic Tx were assessed and approximately 3% of all malignant tumors in adults. RCC is often first significantly longer progression-free survival compared with sunitinib in with aRCC were randomized 1:1 to receive avelumab grouped in the following categories: 4 (10 mg/kg intravenously every 2 weeks) + axitinib (5 mg detected at an advanced stage, with 25% to 30% of patients with patients who received these therapies as 1L Tx for aRCC – SA Tx with VEGF(R) or PD-(L)1 inhibitors or other while receiving avelumab + axitinib metastatic disease at diagnosis1 orally twice daily) or sunitinib (50 mg orally once daily for • There are limited data on the outcomes of patients receiving 2L 4 weeks of a 6-week cycle) – Combination therapy (COMBO) with VEGF(R) inhibitors • Avelumab is a human immunoglobulin G1 (IgG1) monoclonal systemic therapy following immunotherapies plus TKIs in the 1L + other, or any other COMBO (A + Ax) and received subsequent antibody targeting PD-L1 that was approved in combination with • At the cutoff date for the third interim analysis (April 28, axitinib, a VEGFR TKI, for 1L Tx of aRCC2,3 2020), patients who received 1L A + Ax and received any • We report the OS and the time receiving 2L treatment for treatment (Tx) in JAVELIN Renal 101 or no subsequent lines of Tx were assessed these groups using the Kaplan-Meier method

RESULTS

• At the cutoff date for the third interim analysis, 346 of 442 patients • 20 of 204 patients received 2L COMBO with VEGF(R) + other, with the Figure 1. Summary of 2L anticancer drug therapy (78.3%) in the A + Ax arm discontinued treatment with avelumab, and combination of lenvatinib + everolimus being more frequently used, 338 of 442 (76.5%) discontinued axitinib (Table 1) while 21 of 204 patients received any other COMBO L. Albiges,1 M. H. Voss,2 B. I. Rini,3 G. Gravis,4 M.O. Grimm,5 P. Nathan,6 n=21 G. Bjarnason,7 Y. Tomita,8 K. Penkov,9 B. McGregor,10 B. Huang,11 D. Thomaidou,12 • At least one 2L anticancer drug therapy was received by 204 of 442 • The median OS in patients receiving 2L COMBO VEGF(R) + other or any (10.3%) M. Mariani,13 A. di Pietro,13 T. K. Choueiri,10 (46.2%) patients following A + Ax Tx (Table 2) other COMBO was not reached in either arm (Table 3), and the median time on treatment was 12.9 months (95% CI, 8.3-NE) and 11.1 months 1Gustave Roussy Cancer Campus, University of Paris Saclay, Villejuif, France; 2Memorial Sloan Kettering Cancer Center, New York, NY, USA; • The most common 2L Tx was SA VEGF(R) received by 132 of 204 n=20 3Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 4Institut Paoli-Calmettes, Department of Medical Oncology, Aix-Marseille University, (95% CI, 3.0-NE), respectively (Table 4) Inserm, CNRS, CRCM, Marseille, France; 5Department of Urology, Jena University Hospital, Jena, Germany; 6The Mount Vernon Cancer Centre, patients, and cabozantinib was the most frequently used SA VEGF(R) (9.8%) Northwood, Middlesex, UK; 7Sunnybrook Odette Cancer Centre, Toronto, ON, Canada; 8Niigata University Graduate School of Medicine, Niigata, Japan; 9Private Medical Institution, Euromedservice, St Petersburg, Russian Federation; 10Dana-Farber Cancer Institute, Boston, MA, USA; TKI Tx • 124 patients discontinued A + Ax without receiving subsequent 11Pfizer, Groton, CT;12 Pfizer, Athens, Greece; 13Pfizer SRL, Milan, Italy anticancer drug therapies. The median OS in this group was 21.3 • 2L SA PD-(L)1 Tx was given in 19 of 204 patients, with nivolumab being months (95% CI, 13.3-29.7) (Table 5) the most frequently used agent n=12 SA VEG(R) (5.9%) • The median OS in patients receiving 2L SA VEGF(R) or PD-(L)1 inhibitors Table 3. Summary of OS in patients who received subsequent treatment SA PD-()1 was 29.8 months (95% CI, 24.1-42.2) and not evaluable (NE), respectively Single agent (N=163)* Combination therapy (N=41) Other SA (Table 3), and the median time on Tx was 12.1 months (95% CI, 8.4-NE) VEGF(R) PD-(L)1 VEGF(R) + others Any other n=19 SCOPE and 8.9 months (95% CI, 2.3-NE), respectively (Table 4) (n=132) (n=19) (n=20) combination (n=21) n=132 VEG(R) others (9.3%) Patients with event, n (%) 73 (55.3) 8 (42.1) 8 (40.0) 6 (28.6) (64.%) • We describe the outcomes of patients with advanced renal cell Any other COMBO Table 1. Summary of reason for discontinuation of A + Ax Patients censored, n (%) 59 (44.7) 11 (57.9) 12 (60.0) 15 (71.4)

carcinoma (aRCC) who received first line A + Ax in the phase 3 Avelumab Axitinib Probability of being (N=442) (N=442) JAVELIN Renal 101 trial (NCT02684006) and went on to receive event free (95% CI) Discontinued, n (%) 346 (78.3) 338 (76.5) At 12 months 0.854 (0.781-0.904) 0.895 (0.641-0.973) 1.000 (1.000-1.000) 0.905 (0.670-0.975) At 18 months 0.739 (0.654-0.806) 0.895 (0.641-0.973) 0.850 (0.604-0.949) 0.854 (0.613-0.951) subsequent Tx Reason for discontinuation, n (%) At 24 months 0.592 (0.503-0.671) 0.684 (0.428-0.844) 0.750 (0.500-0.887) 0.754 (0.506-0.890) Death 22 (5.0) 24 (5.4) At 36 months 0.416 (0.324-0.505) 0.568 (0.317-0.757) 0.551 (0.288-0.751) 0.700 (0.449-0.853) Progressive disease 175 (39.6) 187 (42.3) OS (95% CI), months Adverse event 98 (22.2) 67 (15.2) Q1 17.7 (15.1-21.3) 21.1 (4.2-NE) 26.4 (14.2-NE) 27.7 (6.4-NE) Median 29.8 (24.1-42.2) NE (21.1-NE) NE (23.3-NE) NE (27.7-NE) CONCLUSIONS Physician decision 8 (1.8) 6 (1.4) Q3 NE (42.2-NE) NE (NE-NE) NE (NE-NE) NE (NE-NE) Global deterioration of health status 15 (3.4) 20 (4.5) • In patients with aRCC who received second-line (2L) therapies NE, not evaluable; OS, overall survival; VEGF(R), vascular endothelial growth factor (receptor). COMBO, combination therapy; SA, single agent; VEGF(R), vascular endothelial growth factor (receptor). Withdrawal of patient 15 (3.4) 19 (4.3) *Twelve patients in the single-agent arm did not receive therapy with VEGF(R) or PD-(L)1 inhibitors and were following first-line (1L) Tx with A + Ax, single-agent (SA) vascular not included in analysis. Study related* 8 (1.8) 9 (2.0) endothelial growth factor (receptor) (VEGF[R]) inhibitor was the Other 5 (1.1) 6 (1.4) Figure 2. Summary of OS most frequent therapy Ongoing n, (%) 96 (21.7) 104 (23.5) Table 4. Summary of time on 2L treatment Median OS (95% CI), months No anticancer drug Tx 21.3 (13.3-29.7) A, avelumab; Ax, axitinib. Single agent (N=163) Combination therapy (N=41) *Includes non-compliance with study drug, protocol deviation, and no longer meets eligibility criteria. SA VEGF(R) 29.8 (24.1-42.2) • The overall survival (OS) in patients receiving 2L treatment was VEGF(R) PD-(L)1 VEGF(R) + others Any other (n=132) (n=19) (n=20) combination (n=21) SA PD-(L)1 NE (21.1-NE) 100 VEGF(R) + others NE (23.3-NE) longer compared with patients who discontinued A + Ax and did Discontinuation of 2L treatment Table 2. Summary of follow-up anticancer therapies 67 (50.8) 11 (57.9) 10 (50.0) 10 (47.6) event, n (%) 90 Any other COMBO NE (27.7-NE) not receive any subsequent Tx Avelumab + axitinib Sunitinib Discontinued, n (%) (N=442) (N=444) Patients censored, n (%) 65 (49.2) 8 (42.1) 10 (50.0) 11 (52.4) 80 Patients who received ≥1 follow-up anticancer drug therapy, n (%) 70 Median time to discontinuation of 2L • Our findings suggest that the use of 2L treatment upon 12.1 (8.4-NE) 8.9 (2.3-NE) 12.9 (8.3-NE) 11.1 (3.0-NE) Yes 204 (46.2) 269 (60.6) treatment (95% CI), months 60

discontinuation of the combination of a checkpoint inhibitor No 63 (14.3) 60 (13.5) S, % 2L, second line; NE, not evaluable; VEGF(R), vascular endothelial growth factor (receptor). O 50 and a VEGFR tyrosine kinase inhibitor (TKI) is likely to provide a Not reported 175 (39.6) 115 (25.9) 40 Follow-up anticancer drug therapy regimens, n (%) benefit, although further studies are warranted to establish the Table 5. Summary of OS in patients who discontinued A + Ax and did not 30 0 regimens 63 (14.3) 60 (13.5) receive subsequent anticancer drug therapy 20 optimal sequence of Tx 1 regimen 135 (30.5) 161 (36.3) 10 2 regimens 46 (10.4) 62 (14.0) No subsequent anticancer drug therapy (N=124) 0 3 regimens 13 (2.9) 31 (7.0) Patients with event, n (%) 71 (57.3) 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 ≥4 regimens 10 (2.3) 15 (3.4) Patients censored, n (%) 53 (42.7) Not reported 175 (39.6) 115 (25.9) Months Probability of being event free (95% CI) GET POSTER PDF Patients who received ≥1 follow-up anticancer radiotherapy, n (%) At 12 months 0.673 (0.577-0.753) No. at risk Copies of this poster obtained through this hyperlink or GET PLAIN LANGUAGE SUMMARY Yes 80 (18.1) 76 (17.1) At 18 months 0.550 (0.451-0.638) quick response (QR) code are for personal use only and No anticancer drug Tx 124 108 98 92 82 78 71 60 58 57 52 48 45 42 41 31 22 13 9 6 5 3 0 At 24 months 0.450 (0.353-0.542) may not be reproduced without permission from ASCO Please scan this quick response (QR) code with No 173 (39.1) 224 (50.5) and the author of this poster your smartphone app or click here to view a plain At 36 months 0.320 (0.228-0.416) SA VEGF(R) 132 131 127 126 123 116 111 110 103 96 92 85 76 69 63 52 40 33 22 16 14 6 1 0 Not reported 189 (42.8) 144 (32.4) language summary of the accepted scientific SA PD-(L)1 19 19 19 18 17 17 17 17 17 17 15 13 13 13 12 10 8 8 7 6 6 2 2 0 abstract Patients who received ≥1 follow-up anticancer surgery, n (%) OS (95% CI), months Correspondence: Q1 9.0 (6.7-12.2) VEGF(R) + others 20 20 20 20 20 20 20 20 19 17 17 16 15 14 14 11 8 5 3 1 1 1 1 0 Laurence Albiges, [email protected] Yes 29 (6.6) 32 (7.2) Median 21.3 (13.3-29.7) No 216 (48.9) 262 (59.0) Q3 NE (31.2- NE) Any other COMBO 21 21 21 21 20 20 19 19 19 17 16 16 15 15 13 13 11 9 6 2 2 2 0

Not reported 197 (44.6) 150 (33.8) A, avelumab; Ax, axitinib; NE, not evaluable; OS, overall survival. COMBO, combination therapy; NE, not evaluable; SA, single agent; Tx, treatment; VEGF(R), vascular endothelial growth factor (receptor).

REFERENCES 1. Gupta K, et al. Cancer Treat Rev. 2008;34(3):193-205. 2. Bavencio (avelumab) [prescribing information]. EMD Serono, Inc., and Pfizer, Inc; 2018.3. Inlyta (axitinib) [prescribing information]. Pfizer Labs; 2020. 4. Motzer RJ, et al. N Engl J Med. 2019;380(12):1103-15. DISCLOSURES L. Albiges has served in consulting or advisory roles for the institute from Amgen, Bristol Myers Squibb, Ipsen, Roche, Novartis, Pfizer, Astellas Pharma, Merck & Co, MSD , AstraZeneca, Exelixis, Corvus Pharmaceuticals, Peloton Therapeutics, and Janssen; has received research funding from Bristol Myers Squibb (Inst); and has received reimbursement for travel and accommodations expenses from Bristol Myers Squibb and MSD. M. H. Voss holds stock and other ownership interests in CellGenix; has received honoraria from Bristol Myers Squibb; has served in a consulting or advisory role for AVEO, Calithera Biosciences, Corvus Pharmaceuticals, Eisai, Exelixis, MSD, and Pfizer; has received research funding from Pfizer; has received reimbursement for travel and accommodations expenses from AstraZeneca/MedImmune; and has other relationship with Bristol Myers Squibb.B. I. Rini holds stock and other ownership interests in PTC Therapeutics; has served in consulting or advisory roles for Bristol Myers Squibb, Pfizer, GNE/Roche, AVEO, Synthorx, Compugen, Merck & Co., Corvus, Surface Oncology, 3D Medicines, Aravive, Alkermes, Arrowhead, GSK, and Shionogi; has received research funding from Pfizer, Merck & Co. GNE/Roche, AVEO, AstraZeneca, Bristol Myers Squibb, and Exelixis; and has received reimbursement for travel and accommodations expenses from Merck & Co., Pfizer, and Bristol Myers Squibb.G. Gravis has received reimbursement for travel and accommodations expenses from Janssen Oncology, Bristol Myers Squibb, Astellas Pharma, Pfizer, Ipsen, and Sanofi.M-O Grimm has served in consulting or advisory roles for AstraZeneca, Bristol Myers Squibb, Ipsen, MSD, Ono Pharmaceitical, Pfizer, Astellas Pharma, EUSA Pharma; has received reimbursement for travel and accommodations expenses from Bristol Myers Squibb and Merck Serono; has received honoraria from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Medac, MSD, Ono Pharmaceutical. Novartis, Pfizer, Ipsen, Merck Serono, and EUSA Pharma; has received research funding from Bristol Myers Squibb (Inst), and Intuitive Surgical (Inst).P. Nathan has served in consulting or advisory roles for AstraZeneca, Bristol Myers Squibb, MSD, Immunocore, Pfizer, Pierre Fabre, Novartis, GSK, Ipsen, 4SC, Merck; has served on a speaker’s bureau for Bristol Myers Squibb, Novartis, MSD, and Merck Serono Ltd; has received reimbursement for travel and accommodations expenses from Bristol Myers Squibb and MSD. G. Bjarnason has served in consulting or advisory roles for Pfizer, Novartis, Bristol Myers Squibb, Eisai, and Ipsen; has received reimbursement for travel and accommodations expenses from Pfizer and Novartis; holds stock and other ownership interests in Merck KGaA; has received honoraria from Pfizer, Novartis, Bristol Myers Squibb, Eisai, and Ipsen; has received research funding from Pfizer (Inst) and Merck KGaA.Y. Tomita has received honoraria from Pfizer, Astellas Pharma, Novartis, Ono Pharmaceutical, Bristol Myers Squibb, and Chugai Pharma; has served in consulting or advisory roles for Novartis, Ono Pharmaceutical, and Taiho Pharmaceutical; has received research funding from Pfizer, Ono Pharmaceutical, Takeda, Astellas Pharma, AstraZeneca, Novartis, and Chugai Pharma (Inst).K. Penkov has received honoraria from Roche, Pfizer, Nektar, MSD, Regeneron, and AstraZeneca; has served in a consulting or advisory role for Nektar.B. McGregor has served in a consulting role for Bayer, Astellas, AstraZeneca, Seattle Genetics, Exelixis, Nektar, Pfizer, Janssen, Genentech, Eisai, Dendreon, Bristol Myers Squibb, and EMD Serono; and has received research funding to the institution from Bristol Myers Squibb, Calithera, Exelixis, and Seattle Genetics. B. Huang is an employee of Pfizer.D. Thomaidou is an employee of Pfizer.M. Mariani is an employee of Pfizer; and holds stock and other ownership interests in Pfizer.A. di Pietro is an employee of Pfizer; and hold stock and other ownership interests in Pfizer. T. K. Choueiri owns stock and has received additional ownership interests from Pionyr and Tempest Therapeutics; has received honoraria from Alexion Pharmaceuticals, Alligent, Analysis Group, American Society of Clinical Oncology (ASCO), AstraZeneca, Bayer, Bristol Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, GlaxoSmithKline, Harborside Press, HERON, Ipsen, Kidney Cancer Association, Lancet Oncology, Lilly, Lpath, MSD, Michael J. Hennessy Associates, Navinata Health, National Comprehensive Cancer Network (NCCN), Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Sanofi-Aventis,The New England Journal of Medicine, and UpToDate; has served in consulting or advisory roles for Alexion Pharmaceuticals, Alligent, Analysis Group, ASCO, AstraZeneca, Bayer, Bristol Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono, European Society Medical Oncology, Exelixis, Foundation Medicine, GlaxoSmithKline, Harborside Press, HERON, Ipsen; Kidney Cancer Association, Lancet Oncology, Lilly, Lpath; MSD, Michael J. Hennessy Associates, Navinata Health, NCCN, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Roche/Genentech, Sanofi-Aventis,The New England Journal of Medicine, and UpToDate; has received research funding from Agensys (Inst), Analysis Group (Inst), AstraZeneca (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Calithera Biosciences (Inst), Celldex (Inst), Cerulean Pharma (Inst), Congressionally Directed Medical Research Programs (DOD) (Inst), Corvus Pharmaceuticals (Inst), Eisai (Inst), Exelixis (Inst), Foundation Medicine (Inst), Gateway for Cancer Research (Inst), GlaxoSmithKline (Inst), Ipsen (Inst), MSD (Inst), NCI (Inst), Novartis (Inst), Peloton Therapeutics (Inst), Pfizer (Inst), Prometheus (Inst), Roche (Inst), Roche/Genentech (Inst), Seattle Genetics/Astellas (Inst), Takeda (Inst), and TRACON Pharma; (Inst); owns patents, royalties, or other intellectual property for International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy; International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response; and has received reimbursement for travel and accommodations expenses from Alexion Pharmaceuticals, Alligent, Analysis Group, AstraZeneca, Bayer, Bristol Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono, ESMO, Exelixis, Foundation Medicine, GlaxoSmithKline, Harborside Press, HERON, Ipsen, Kidney Cancer Association, Lancet Oncology, Lilly, Lpath, MSD, Michael J. Hennessy Associates, Navinata Health, NCCN, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Roche/Genentech, Sanofi-Aventis,The New England Journal of Medicine, and UpToDate. ACKNOWLEDGMENTS The authors would like to thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers and at Pfizer. This trial was sponsored by Pfizer and is part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany. Medical writing support was provided by Samil Patel of ClinicalThinking, and was funded by Pfizer and Merck KGaA.

Abstract No. 4514. Presented at 2021 ASCO Annual Meeting, June 4-8, 2021; Virtual.