Celldex Therapeutics, Inc. · NASDAQ:CLDX
Celldex Therapeutics — Technical Presentation (November 2013)
20 slides from Celldex Therapeutics's technical presentation, November 2013
Slide 1: ReACT: A Phase II Study of Rindopepimut Vaccine Plus Bevacizumab in Relapsed GBM
ReACT: A Phase II Study of Rindopepimut Vaccine (CDX-110) Plus Bevacizumab in Relapsed Glioblastoma (GBM) David A. Reardon1, Gordon Li2, Lawrence Recht2, Karen Fink3, Louis Nabors4, David Tran5, Annick Desjardins6, Nitin Chandramouli 7, J. Paul Duic8, Morris Groves9, Anne Clarke10, Thomas Hawthorne1
Slide 2: EGFR Mutation Variant III (EGFRvIII)
EGFR Mutation Variant III (EGFRvIII) • Tumor-specific oncogene expressed in one-third of primary GBM, seldom expressed with IDH mutations but not in normal tissue • EGFRvIII(+) cells may induce growth in EGFRvIII(-) cells via paracrine signaling, membrane-derived microvesicles, and tumor stem cells1
Slide 3: Rindopepimut: Long-Term Follow-up from Phase 2 Trials in de novo GBM
Rindopepimut: Long-Term Follow-up from Phase 2 Trials in de novo GBM • Three Phase 2 Studies: ACTIVATE (n=18), ACT II (n = 22), ACT III (n=65) ‒ Newly diagnosed, resected, EGFRvIII-expressing GBM • Significant anti-EGFRvIII immunity in 85% of ACT III patients (67% > 1:12,800). • EGFRvIII eliminated
Slide 4: Rationale for Rindopepimut Plus Bevacizumab in Relapsed GBM
Rationale for Rindopepimut Plus Bevacizumab in Relapsed GBM • Anecdotal evidence suggest that Bevacizumab-experienced patients rindopepimut may induce specific are historically difficult to treat immune responses and regression Treatment ORR PFS6 Median Median in multifocal and bulky tumors (%) (%)
Slide 5: Phase II ReACT Study Design
Phase II “ReACT” Study Design Study vaccine + Bevacizumab naïve (n=70): Randomization (1:1) bevacizumab No prior bevacizumab or VEGF/ VEGF receptor-targeted agents Double-blind Control + treatment bevacizumab Bevacizumab refractory (n=25): Open-label treatment Study vaccine + Progression during or w
Slide 6: Phase II ReACT Study Design
Phase II “ReACT” Study Design Eligibility • 1st or 2nd relapse of GBM • EGFRvIII+ (as per centralized IDE-approved RT-PCR assay) • Prior conventional radiation and temozolomide • No radiation within 3 months of entry • Systemic corticosteroid therapy ≤ 4 mg of dexamethasone daily • No metastatic dis
Slide 7: ReACT Study Status
“ReACT” Study Status Bevacizumab-refractory Data evaluation • Enrollment to initial cohort is complete; 25 • Investigator assessment of tumor response patients treated (according to RANO - 1 patient continues to receive treatment criteria) complete. - A total of 6 patients continue to be followed •
Slide 8: Patient Characteristics
Patient Characteristics Bevacizumab Bevacizumab Naïve Refractory Study Vaccine + Control + (n=25) Bevacizumab Bevacizumab (n=20) (n=20) Age, years (median [range]) 58 (39-79) 60 (51-79) 56 (30-75) ≥50 years (n [%]) 20 (80%) 20 (100%) 15 (75%) Male (n [%]) 16 (64%) 9 (45%) 11 (55%) KPS (n [%]) 100 1
Slide 9: Safety
Safety Bevacizumab-Refractory and Bevacizumab Naïve Relapsed GBM • Rindopepimut plus bevacizumab (dosing for up to 13 months) has been well-tolerated • No unexpected toxicity associated with concomitant bevacizumab administration • No treatment-related toxicity resulting in discontinuation of study
Slide 10: Robust Anti-EGFR Immunity in Patients Receiving Rindopepimut plus Bevacizumab
Robust Anti-EGFR Immunity in Patients Receiving Rindopepimut plus Bevacizumab • 4-fold increase over baseline in anti-EGFRvIII antibody titers in 79% of bev-refractory and Anti-EGFRvIII Antibody Titers 84% of bev-naïve patients 100,000,000 10,000,000 ‒ Remaining patients received 1,000,000 treatment
Slide 11: Anti-Tumor Effect
Anti-Tumor Effect Bevacizumab-Refractory Relapsed GBM • ITT analysis of primary endpoint: 2/25 (8%) patients receiving rindopepimut + bevacizumab were progression-free at 6 months – Study designed with an ambitious goal of PFS6 = 20% – No comparative data available to define expected outcome for EGF
Slide 12: Tumor Response in Bevacizumab-Refractory Relapsed GBM
Tumor Response in Bevacizumab-Refractory Relapsed GBM Pre-Rindopepimut 63 yr, female with PD after XRT/TMZ and 7 cycles of adjuvant TMZ; then 2nd PD after 3.5 months on BEV monotherapy Ongoing response after 5 cycles of Rindopepimut + BEV Patient continues to be progression free, currently at 8+ mon
Slide 13: Maximum Shrinkage of Target Lesions
Tumor Shrinkage Bevacizumab-Refractory Relapsed GBM > 200% 175% Maximum Shrinkage of Target Lesions 150% 125% 100% 75% 50% 25% PD 0% ‐25% ‐50% PR ‐75% ‐100% * * Data from Investigator Read * Previously treated with bevacizumab but did not have progression within 2 months of 13 discontinuation.
Slide 14: Progression-Free and Overall Survival
Progression-Free and Overall Survival Bevacizumab-Refractory Relapsed GBM Median, 6-Month Months Rate (95% CI) (%) Overall Survival 5.6 (3.2, 6.7) 48% Progression-free 1.9 (1.8, 2.8) 8% Survival PFS based on Investigator Review Median follow-up: 10.0 months 14
Slide 15: Preliminary Analysis of Anti-Tumor Effect Bevacizumab-Naive Relapsed GBM
Preliminary Analysis of Anti-Tumor Effect Bevacizumab-Naïve Relapsed GBM Study Vaccine + Control + Bevacizumab Bevacizumab Stable disease or better for 14/20 (70%) 11/20 (55%) ≥ 2 months Steroids initiated or increased 1/20 (5%) 7/20 (35%) (1st adjustment) ORR (confirmed CR/PR)1,2 3/19 (16%)** 2/16
Slide 16: Maximum Shrinkage of Target Lesions
Tumor Shrinkage Bevacizumab-Naïve Relapsed GBM > 100% 75% Maximum Shrinkage of Target Lesions 50% 25% PD 0% ‐25% ‐50% PR ‐75% ‐100% Study Vaccine + Bevacizumab Control + Bevacizumab 16
Slide 17: Interim Progression-Free and Overall Survival
Interim Progression-Free and Overall Survival Bevacizumab-Naïve Relapsed GBM Median PFS, Median OS, Months (95% CI) Months (95% CI) Study Vaccine + Bevacizumab (n=20) 3.7 (1.9, 3.9) 12.0 (5.8, Not est.) Control + Bevacizumab (n=20) 2.0 (1.9, 5.6) 7.9 (4.1, Not est.) Median follow-up: 6.4 months for
Slide 18: Early Anti-EGFRvIII Response Correlates with Survival in Relapsed GBM
Early Anti-EGFRvIII Response Correlates with Survival in Relapsed GBM Treated with Rindopepimut + Bevacizumab Bevacizumab-Refractory Bevacizumab-Naïve Median OS 6-Month Median OS 6-Month Months (95% CI) OS (%) Months (95% CI) OS (%) Highest Titers* (n=13) 6.6 (3.7, 12.6) 69% Highest Titers* (n=8) No
Slide 19: Conclusions
Conclusions • Rindopepimut combined with bevacizumab was very well tolerated • Remarkable frequency and level of anti-EGFRvIII immune responses were generated despite prior chemotherapy and growing tumor • Encouraging tumor response and survival data – 48% OS rate at 6 months in refractory patients
Slide 20: Acknowledgements
Acknowledgements Atlanta Cancer Care Rhode Island Hospital University of Pennsylvania Expert Review Panel Ron Steis Heinrich Elinzano James Schuster John de Groot Jacqueline Asea Christine Hopkins‐Spidell Bernard Michel Whitney Pope Barrow Neurologic Clinics Stanford University University of Rochest
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