17 slides from Actinium Pharmaceuticals, Inc. (delaware)'s technical presentation, 2023
Slide 1: Efficacy and Safety Results of the SIERRA Trial
Efficacy and Safety Results of the SIERRA Trial: A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Older Patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) Boglarka Gyurkocza, MD, Stuart Serop
Slide 2: Relevant Disclosures
Relevant Disclosures Dr. Boglarka Gyurkocza Dr. Patrick Stiff Dr. Ben Tomlinson Actinium MorphoSys, CRISPR Therapeutics, Amgen, Gamida Cell, Seagen, BMS, Chimerics Karyopharm, Kite, Macrogenics, BMS, Janssen, Pfizer, Gilead, Incyte, Dr. Hannah Choe Cellectar, Actinium Dr. George Chen AbbVie Actinium
Slide 3: Background
Background ⧫ Patients with active, R/R AML have a dismal prognosis, particularly with increasing age, and typically are not offered allogeneic HCT due to failure to achieve remission, poor tolerance of conditioning, and substantial transplant-related mortality ⧫ Iomab-B (Iodine (131I) apamistamab),
Slide 4: SIERRA: Study of Iomab-B in Elderly R/R AML
SIERRA: Study of Iomab-B in Elderly R/R AML Accrual Target: N=150 No CR Endpoints: Iomab-B HCT Pre-Specified Primary: dCR = CR/CRp lasting CR dCR ≥180 days post-CR Crossover* Active, Relapsed *Control arm subjects with Secondary: OS and EFS RANDOMIZED 1:1 no CR offered crossover or Refractory AML No
Slide 5: Personalized Single Dose Combined Induction/Conditioning
Personalized Single Dose Combined Induction/Conditioning RIC Dosimetric Dose Therapeutic Dose FLU TBI ≤20 mCi • Upper limit of 24 Gy to liver 30 mg/m2/d 200 cGy • Median 16 Gy to marrow HCT Day: -19 -18 -15 -12 -4 -3 -2 -1 0 Imaging Tac/CSA + MMF RIC: reduced intensity conditioning; FLU: fludarabine
Slide 6: CONSORT Chart
CONSORT Chart 153 Pts Randomized Iomab-B Conventional Care N=76 N=77 1 pt did not • 4 pts did not receive receive chemo dosimetric dose • 6 pts did not proceed to therapeutic dose with HCT No CR Achieved CR N=62 N=14 66 patients received Crossover to Iomab-B therapeutic dose N=44 4 pts did not proce
Slide 7: Patient Characteristics
Patient Characteristics Complete Enrollment, N = 153 Randomized to Conventional Iomab-B Arm (N=76) Conventional Care Arm (N=77) Care and Crossed Over to Iomab-B (N=44) Age, years Median 64 (55-77) 66 (55-76) 64 (55-76) (Range) Pts ≥70 yrs: 14 (18.4%) Pts ≥70 yrs: 16 (20.8%) Pts ≥70 yrs: 12 (27.3%) C
Slide 8: Conditioning and Transplant Characteristics
Conditioning and Transplant Characteristics Iomab-B (N=66)1 Standard HCT (N=14) Crossover (N=40)2 Infused Activity 664.4 mCi (354-1027) N/A 613.3 mCi (313-1008) Median (Range) Dose to the Marrow 16 Gy (4.6-44.6) N/A 16 Gy (6.3-39.8) Median (Range) Time to HCT From Randomization 29 Days (23-60) 66.5
Slide 9: Superior dCR Rate for Iomab-B versus CC
Superior dCR Rate for Iomab-B versus CC dCR assessed by Independent Endpoint Adjudication Committee Iomab-B CC N (%) N (%) Evaluable Per-Protocol* 59 64 Achieved CR/CRp 44 (74.6) 4 (6.3) Maintained dCR 13 (22.0) 0 (0.0) of ≥180 days p<0.0001; 95% CI [12.29, 34.73] ‒ In the crossover arm (N=44), 91%
Slide 10: Iomab-B Doubles Overall Survival Compared to CC
Iomab-B Doubles Overall Survival Compared to CC Iomab-B (N=76) CC Only (without Crossover) (N=33) Overall Survival (mos) 6.4 (5.1, 7.9) 3.2 (1.6, 7.0) Median (95% CI) One-Year Survival 26.0 (16.7, 36.4) 13.1 (4.2, 27.4) % (95% CI) Duration of Follow-up (mos) 6.3 (0.5-49.5) 3 (0.6-28.8) Median (Range
Slide 11: Iomab-B Superior to CC Across Subgroups
Iomab-B Superior to CC Across Subgroups ⧫ Forest Plot of Hazard Ratios for Overall Survival – Iomab-B, N=76; CC (without Crossover), N=33 1 2 3 1. PIF: Primary induction failure; FER: First early relapse; RR: Relapse refractory; SSR: Second or subsequent relapse. 2. Median 3 prior regimens across bo
Slide 12: Significantly Improved Event-Free Survival with Iomab-B Versus CC
Significantly Improved Event-Free Survival with Iomab-B Versus CC EFS in Intent-to-Treat Groups Iomab-B (N=76) CC (N=77) HR 0.22 (95% CI [0.15, 0.34]) EFS at 180 days 28% 0.2% p<0.0001 Events defined as: ‒ Induction treatment Event-Free Survival Probability (%) failure (ITF), defined as day of rando
Slide 13: Long-Term Survival in Patients with dCR
Long-Term Survival in Patients with dCR Rate of OS at: Iomab-B (N=13) CC (N=0) 6 months 100% 12 months 92.3% NA 18 months 71.9% 24 months 59.9% Overall Survival Probability (%) Time (Months) 13
Slide 14: Favorable Safety Profile for Iomab-B Compared to CC
Favorable Safety Profile for Iomab-B Compared to CC Grade ≥3 Treatment-Emergent Adverse Events in Transplanted Patients Through Day 100 Post-HCT Adverse Event Iomab-B (N=66) CC (N=14) Sepsis1 4 (6.1) 4 (28.6) N (%) Febrile Neutropenia 29 (43.9) 7 (50.0) N (%) Mucositis2 10 (15.2) 3 (21.4) N (%) Acut
Slide 15: Conclusions
Conclusions ⧫ In pts ≥55yrs with active R/R AML, Iomab-B followed immediately by RIC conditioning with fludarabine and low-dose TBI enabled allogeneic HCT in a population not typically eligible for transplant ⧫ Iomab-B was well-tolerated and resulted in engraftment in all treated patients, a high ra
Slide 16: Acknowledgments
The Investigators and Actinium Pharmaceuticals would like to thank all the care teams and staff at the clinical sites for their hard work over the past several years. In particular, we would like to thank our Nuclear Medicine colleagues, whose time and expertise was critical to the successful admini
Slide 17: Thank you
Thank you