Curis, Inc. · NASDAQ:CRIS
Curis — Technical Presentation (2014)
17 slides from Curis's technical presentation, 2014
Slide 1: Long-term safety and efficacy of vismodegib in advanced BCC: 24-month update of ERIVANCE
Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma (BCC): 24-month update of the pivotal ERIVANCE BCC study A Sekulic,1 MR Migden,2 AE Oro,3 L Dirix,4 K Lewis,5 JD Hainsworth,6 JA Solomon,7-9 J Hou,10, B Lyons,10 D Schadendorf11 1Mayo Clinic, Scottsdale, AZ, U
Slide 2: Introduction
2 Introduction • Basal cell carcinoma (BCC) is the most common human malignancy1 • Although most BCCs are amenable to surgery, a small subset progress to become locally advanced (la) or metastatic (m)1 • Therapies for advanced basal cell carcinoma (aBCC) are limited1 • Abnormal Hedgehog (Hh) pathway
Slide 3: ERIVANCE BCC
3 ERIVANCE BCC • ERIVANCE BCC trial was an international, 2-cohort, nonrandomized study in which patients with laBCC or mBCC received 150 mg of oral vismodegib daily. Results from the primary analysis (26 Nov 2010) for the efficacy-evaluable population have been published.1 • Primary endpoint was ob
Slide 4: Study design
4 Study design • Primary end point: ORR by independent review • Secondary end points: investigator-assessed ORR, PFS, DOR, OS, and safety laBCCa aBCC n = 71 Treatment discontinued Enrollment Continuous Patient oral on disease progression, vismodegib intolerable toxicity,c or N = 104 150 mg/day study
Slide 5: Eligibility
5 Eligibility • ≥18 years of age, adequate organ function, ECOG PS ≤2 • laBCC: • ≥1 lesion (longest diameter ≥10 mm) that was considered inoperable, or for which surgery was considered inappropriate because of (1) multiple previous recurrences and low likelihood of cure, or (2) substantial morbidity
Slide 6: Baseline demographics
6 Baseline demographics laBCC mBCC Variable n = 63a n = 33 Age, median (range), yr 62 (21-101) 62 (38-92) Sex, n (%) Male 35 (55.6) 24 (72.7) Female 28 (44.4) 9 (27.3) Race, n (%) White 63 (100) 33 (100) laBCC, n (%) Inoperable 24 (38.1) Surgery inappropriate 39 (61.9) ̶ Multiple previous recurrence
Slide 7: Patient disposition
7 Patient disposition • At data cutoff, 14 (13.5%) patients continued to receive treatment, and 63 (60.6%) patients were in survival follow-up laBCC mBCC All Patients Status n = 71 n = 33 N = 104 Patients still on treatment, n (%) 12 (16.9) 2 (6.1) 14 (13.5) Discontinued treatment, n (%) 59 (83.1) 3
Slide 8: Exposure
8 Exposure • Median dose intensity (97%) was comparable to the primary analysis laBCC mBCC All Patients Exposure n = 71 n = 33 N = 104 Duration of treatment, mo Median 12.7 13.3 12.9 Range (1.1-42.3) (0.7-33.4) (0.7-42.3) Dose intensity, % Median 96.9 98.9 97.4 Range (58.5-107.5) (77.4-102.5) (58.5-
Slide 9: Objective response
9 Objective response All Investigator-Assessed Overall laBCC mBCC Patients Responsea n = 63 n = 33 N = 96d 24-month Primary 24-month Primary 24-month follow-upb analysis1 follow-upc analysis1 follow-up Objective responsee, n (%) 38 (60.3) 38 (60.3) 16 (48.5) 15 (45.5) 54 (56.3) Complete response, n
Slide 10: Progression-free survival and overall survival
Progression-free survival and 10 overall survival laBCC mBCC All Patients Survival n = 63 n = 33 N = 96 Progression-free survival, mo Median 12.9 9.3 12.8 Range 0.0+ – 38.8+ 0.0+ – 32.8 0.0+ – 38.8+ Overall survival, mo Median Not estimable 33.4 Not estimable Range 2.4+ – 43.0+ 6.7 – 40.2+ 2.4+ – 43
Slide 11: Progression-free survival
11 Progression-free survival Kaplan-Meier plot of investigator -assessed progression-free survival (PFS INV) 1.0 + + ++ + + 0.8 ++ +++ + ++ ++ Proportion 0.6 + + 0.4 + + ++ + ++ + + ++ + 0.2 + Metastatic (n = 33) + Locally advanced (n = 63) 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 Number at Risk PF
Slide 12: Overall survival
12 Overall survival Kaplan-Meier plot of investigator-assessed duration of survival 1.0 ++++ + ++ ++ + + + + ++ + + +++++++++++++ ++++ ++++ +++++ 0.8 ++ Proportion 0.6 + + + ++ ++++++ + + + 0.4 0.2 Metastatic (n = 33) Locally advanced (n = 63) 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Number a
Slide 13: Adverse events in >10% of patients by maximum grade
13 Adverse events in >10% of patients by maximum grade NCI CTCAE Grade (N = 104) Adverse Eventa, n (%) Total 1 2 3 4 5 Any adverse event 104† (100) 9 (8.7) 39 (37.5) 35 (33.7) 13 (12.5) 7 (6.7) Muscle spasms 74 (71.2) 46 (44.2) 22 (21.2) 6 (5.8) 0 0 Alopecia 68 (65.4) 48 (46.2) 20 (19.2) 0 0 0 Dysge
Slide 14: Serious adverse events (occurring in ≥2 patients)
Serious adverse events 14 (occurring in ≥2 patients) All Patients Serious Adverse Event, n (%) N = 104 Any 36 (34.6) Syncope 4 (3.8) Hip fracture 3 (2.9) Death 3 (2.9) Pneumonia 3 (2.9) Cardiac failure 2 (1.9) Gastrointestinal hemorrhage 2 (1.9) Cellulitis 2 (1.9) Squamous cell carcinoma 2 (1.9) Pul
Slide 15: Deaths
15 Deaths • In the update period following the primary analysis, 13 additional deaths were reported, leading to a total count of 29 deaths • These occurred during survival follow-up (while the patients were not receiving study drug) and were not considered to be related to vismodegib laBCC mBCC All
Slide 16: Response after long-term vismodegib treatment
Response after long-term 16 vismodegib treatment Screening Week 104
Slide 17: Conclusions
17 Conclusions • Vismodegib is the first approved Hedgehog pathway inhibitor • With longer duration of follow-up, median duration of response approximately tripled in the laBCC cohort compared with the primary analysis • The safety profile of vismodegib remained consistent with that reported in the