S E P T E M B E R 2 7 TH - 29 TH,

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1 Intralesional Injection of the CD47-blocking Immune Checkpoint Inhibitor TTI-621 (SIRPαFc) Induces Antitumor Activity in Patients with Relapsed/Refractory Mycosis Fungoides and Sézary Syndrome: Interim Results of a Multicenter Phase 1 Trial C H R I S T I A N E Q U E R F E L D 1, J O H N A T H O M P S O N 2, M AT T H E W TAY LO R 3, R A J U K P I L L A I 1, L I S A D S J O H N S O N 4, T I N A C ATA L A N O 4, P E N K A S P E T R OVA 4, R O B E R T A U G E R 4, M E G H A N I R W I N 4, T H E R E S A T H O M P S O N 4, E R I C L S I E V E RS 4, YA P I N G S H O U 4, O L EG A K I LOV 5 1 C I T Y O F H O P E, D U A R T E, C A, U S A ; 2 U N I V E R S I T Y O F WA S H I N G TO N / S C C A, S E AT T L E, WA, U S A ; 3 O R E G O N H E A LT H A N D S C I E N C E U N I V E R S I T Y, P O R T L A N D, O R, U S A ; 4 T R I L L I U M T H E R A P E U T I C S I N C., M I S S I S S A U G A, O N TA R I O, C A N A D A ; 5 U N I V E R S I T Y O F P I T T S B U R G H M E D I C A L C E N T E R, P I T T S B U R G H, PA, U S A S E P T E M B E R 2 7 TH - 29 TH, 2 1 8

2 Conflict of Interest Research Support/P.I. Celgene Employee - Consultant - Major Stockholder Speakers Bureau Honoraria miragen, Medivir, Kyowa Kirin, Actelion Scientific Advisory Board Trillium, miragen, Medivir, Bioniz, Kyowa Kirin, Actelion 2

3 Many Tumor Cells use the CD47 Do Not Eat Signal to Inhibit Macrophage Phagocytosis CD47 delivers an inhibitory do not eat signal to macrophages through SIRPα Many hematologic and solid tumors express high levels of CD47 High CD47 expression often correlates with aggressive disease and poor clinical outcomes 3

4 TTI-621: A Dual Function SIRPαFc Decoy Receptor that Blocks CD47 and Delivers an Activating Signal Blocks the CD47 DO NOT EAT signal Delivers an EAT signal through FcγRs 4

5 TTI-621 Activates both Innate and Adaptive Immune Systems 5

6 TTI Study Overview Study Population Solid tumors w percutaneous lesions & CTCL Dose Escalation Phase Modified 3+3 scheme Maximum 2 week induction treatment Dose Expansion Phase Injection of multiple lesions permitted Continuation therapy (weekly injections post-induction) at Investigator s discretion Data Cut: August 3, 218 6

7 Baseline Characteristics in CTCL Subjects Disease stages IA through IVB are included All subjects received prior local and/or systemic therapies Subjects received a median of 3 prior systemic treatments Data Cut-off: August 3, 218 7

8 Intralesional TTI-621 Injections were Well Tolerated Related adverse events (AEs) all Grade 1 or 2; no Grade 3 AEs Common related AEs include chills, injection site pain, and fatigue No related serious adverse events (SAEs) or dose-limiting toxicity Data Cut-off: August 3, 218 8

9 CAILS Reduction in Injected Lesions were Observed in Majority of Patients 18 Patients have available CAILS scores 16 (89%) with decreased CAILS 8 (44%) with 5% reduction in CAILS CAILS decreases: Occurred at all dose levels Following single and multiple injections In all stages IA to IVB Data Cut-off: August 3, 218 9

10 C A IL S C h a n g e (% ) fro m B a se lin e CAILS Responses Occurred Rapidly within the 2-Week Induction Period C A IL S % D e c r e a s e in In d u c t io n T h e r a p y P a tie n ts* 2 C o h o r t 1 (s in g le in je c tio n 1 m g ) C o h o r t 2 (s in g le in je c tio n 3 m g ) -2 C o h o r t 3 (s in g le in je c t io n 1 m g ) -4 C o h o r t 4 (m u ltip le in je c t io n s 1 m g M W F x 1 w k ) # D a y 1 4 C o h o rt 5 (m u lt ip le in je c t io n s 1 m g M W F x 2 w k s) C o h o rt 7 (m u lt ip le in je c tio n s m u litp le le s io n s 1 m g M W F x 2 w k s) S tu d y D a y * Patients received maximally 2 weeks of study treatment (induction phase) Response assessments beyond day 14 are provided if patients have not progressed or continued onto another therapy # The first patient treated obtained a CR of the injected lesion that is ongoing after 52+ weeks Data Cut-off: August 3, 218 1

11 Local-Regional Responses were Observed in Non-injected, Adjacent Control Lesions Change (%) Change (%) Change (%) Change (%) Change (%) Change (%) 1 5 1mg Single Injection CAILS Change (%) from Baseline in Injected vs Non-Injected paired control lesions 7 patients with reduced CAILS had a paired CAILS assessments in an adjacent non-injected lesion mg MWF x mg MWF x 2 Injected lesion CAILS decreased -14% to -67% in all patients Non-injected lesion CAILS decreased -12% to -67% in 6/7 patients Median distance between paired injected and non-injected lesions is estimated to be 5.3 cm (range.2-15 cm) 5 1mg MWF x 2 5 1mg MWF x 2 All CAILS scores: Injected vs Non-Injected Control Lesions Injected Control 1 5 1mg MWF x Study Day Data Cut-off: August 3,

12 Abscopal (Systemic) Effects were Observed in One of Two Patients Receiving Continuation Monotherapy Injected Lesion T1 (Left Calf) Rapid resolution of lesions on abdomen (lower panel), left flank/back and arms (not shown) following TTI-621 injections of target lesions on left calf (upper panel), left ankle and right foot. Screening Week 2 Week 7 Week 11 Distal Non-Injected Lesion Abdomen Screening Week 2 Week 2 Week 9 Data Cut-off: August 3,

13 V 9 + o f C D 4 + (% ) C D 4 :C D 8 C D 4 :C D 8 Peripheral Responses were Observed Following Local Injections Single 1 mg Injection Single 1 mg Injection Single 3 mg Injection Screening Day 8 S e z a r y C e ll C o u n t Screening Day 8 C D 4 :C D 8 Screening Day 8 C D 4 :C D P r e - T r e a t m e n t D a y 3 D a y 8 P r e - T r e a t m e n t D a y 8 P r e - T r e a t m e n t D a y 8 13

14 Intralesional TTI PEG-IFNα2a Resulted in More Rapid Systemic Effects than Expected for PEG-IFNα2a Alone TTI-621: Single 3 mg Injection (Week 1) PEG-IFN-α2a: Two 9 mg Injections (Week 2-3) TTI-621: Multiple 1 mg Injections MWF x 2 (Week 1-2) PEG-IFN-α2a: Two 9 mg Injections (Week 3-4) Screening Week 2 Week 4 Screening Week 5 14

15 Conclusions Single and multiple intralesional injections of up to 1 mg TTI-621 have been well tolerated All treatment-related AEs were Grade 1 or 2 in severity No treatment-related SAEs or dose-limiting toxicity have been observed CAILS-based local effects were observed in injected lesions in majority of heavily pretreated MF/SS patients across various disease stages 89% of patients with available CAILS data had a reduction in CAILS; 44% had 5% CAILS decrease Responses were rapid and in some patients, occurring after a single injection of varying doses Similar CAILS-based changes were seen in adjacent, non-injected lesions suggesting the local regional effect may not be confined to the site of injection Initial evidence of distal abscopal or systemic effect was observed in one of two patients receiving continuation monotherapy Continued weekly injections after the 2-week induction and rolling injection of additional lesions may offer higher probability to introduce systemic effect Initial experience with PEG-IFNα2a is suggestive of combination effect Translational studies are ongoing and initial data suggest modulation of innate immune system in tumor biopsies 15

16 Acknowledgement The authors would like to thank: The patients who participated in this study and their families The staff members who contributed to the conduct of the study and development of this presentation City of Hope Cancer Center University of Pittsburg Medical Center Oregon Health & Science University Knight Cancer Institute University of Washington Seattle Cancer Care Alliance Trillium Therapeutics Inc., Sponsor Sarah Cannon Development Innovations, CRO 16