ASH 2023: Iomab-B Produces Long Term Remissions Irrespective of Multiple High-Risk Features

65th ASH Annual	131I-apamistamab Effectively Achieved Durable Responses in Patients with
Meeting & Exposition
San Diego, CA	R/R AML Irrespective of the Presence of Multiple High-Risk Factors
Dec 9-12, 2023
PUBLICATION #2159	Stuart Seropian, MD1, James Foran, MD2, Boglarka Gyurkocza, MD3, Rajneesh Nath, MD4, Hannah Choe, MD5, Mark R. Litzow, MD6, Nebu Koshy, MD7, Patrick J. Stiff, MD8, Ben K. Tomlinson, MD9, Sunil Abhyankar, MD10, Sameem Abedin, MD11, George Chen, MD12,13, Zaid Al-Kadhimi,
	MD14,15, Partow Kebriaei, MD16, Mitchell Sabloff, MSc, MD, FRCPC17, Johnnie J. Orozco, MD, PhD18, Katarzyna Joanna Jamieson, MD19, Margarida Magalhaes-Silverman, MD20, Koen Van Besien, MD, PhD21,22, Michael W. Schuster, MD23, Arjun D. Law, MD24, Sebastian A. Mayer, MD25,
	Hillard M. Lazarus, MD26, Jennifer Spross, MA27, Kate L Li, PhD27, Elaina Haeuber, MS27, Madhuri Vusirikala, MD27, Akash Nahar, MD, MPH27, Brenda M. Sandmaier, MD28, John M. Pagel, MD, PhD29, Sergio A. Giralt, MD30, Avinash Desai, MD27 and Camille N. Abboud, MD31

1.Yale Univ. School of Med., New Haven, CT; 2.Hematology/Oncology, Mayo Clinic, Jacksonville, FL; 3.Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; 4.Banner MD Anderson Cancer Center, Scottsdale, AZ; 5.The James Cancer Hospital Solove Research Institute and The Ohio State University Wexner Medical Center, Columbus, OH; 6.Division of Hematology, Mayo Clinic, Rochester, MN; 7.Texas Oncology Baylor Charles A. Sammons Cancer Center, Dallas, TX; 8.Division of Hematology and Oncology, Loyola University Medical Center, Maywood, IL; 9.University Hospitals Seidman Cancer Center, Cleveland, OH; 10.University of Kansas Medical Center, Westwood, KS; 11.Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI; 12.MD Anderson Cancer Center, Houston, TX; 13.Roswell Park Comprehensive Cancer Center, Buffalo, NY; 14.University of Alabama at Birmingham, Birmingham, AL; 15.University of Nebraska Medical Center, Omaha, NE; 16.Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; 17.Ottawa Hospital, Ottawa, ON, CAN; 18.Translational Science and Therapeutics Division, Fred Hutch Cancer Research Center, Seattle, WA; 19.University of North Carolina, Chapel Hill, NC; 20.Holden Comprehensive Cancer Center, University of Iowa Hospital and Clinics, Iowa City, IA; 21.Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY; 22.Weill Cornell Medical College, New York, NY; 23.Stony Brook University Cancer Center, Stony Brook, NY; 24.Hans Messner Allogenic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; 25.Weill Cornell Medical Center, New York, NY; 26.Case Western Reserve University, Cleveland, OH; 27.Actinium Pharmaceuticals, New York, NY; 28.Fred Hutchinson Cancer Center, Clinical Research Division; University of Washington School of Medicine, Seattle, WA; 29.Loxo Oncology at Lilly, Stamford, CT; 30.Memorial Sloan Kettering Cancer Center, New York, NY; 31.Washington University School of Medicine, Saint Louis, MO

Background

SIERRA Iomab-B Treatment Schedule

Rate of dCR Stratified by Number of Risk Factors

Most older patients with relapsed/refractory (R/R) AML cannot tolerate intensive treatment and are not eligible for curative allogeneic hematopoietic cell transplant (HCT).

131I-apamistamab delivers high dose targeted radiation to hematopoietic cells, allowing for myeloablation and eradication of leukemic cells while sparing toxicity to healthy organs.

131I-apamistamab-based novel induction/conditioning can thus provide these high-risk patients with access to allogeneic HCT.

Objective

11% (4/35 pts)

14% (9/63 pts)

Risk Factors Assessed:

• Adverse-RiskCytogenetics
• Age >65 years
• Prior treatment failure with Venetoclax
• HCT Comorbidity Index ≥3
• KPS <90

27% (6/22 pts)

We analyzed the rate of durable complete response (dCR) in patients with high-risk factors, such as adverse risk cytogenetics, age >65, prior treatment failure with venetoclax, high HCT comorbidity index, or reduced KPS. We compared the rate of dCR across subgroups in the presence of one or more of these high-risk factors.

131I-apamistamab(Iomab-B)

Iomab-B targets CD45, expressed on hematopoietic cells, including the majority of malignant myeloid and lymphoid cells. Iomab-B delivers targeted radiation directly to leukemic cells and avoids non-targeted tissue.

Study Design: SIERRA was a controlled, optional one-way crossover study of Iomab-B versus Investigator's choice of salvage therapy in patients aged 55 years or older with active, R/R AML. Patients randomized to Conventional Care (CC) who achieve CR could proceed to allogeneic HCT or other standard treatment. Patients not achieving CR could crossover to Iomab-B.

Patient Characteristics dCR vs. non-dCR

Overall Survival Favors Iomab-B Across Most Subgroups

Overall Survival: Iomab-B, N=76; CC (Excluding Crossover), N=33

1. PIF: Primary induction failure; FER: First early relapse; RR: Relapse refractory; SSR: Second or subsequent relapse.
2. Median 3 prior regimens across both treatment groups for the Intent-to-Treat Analysis set
3. Median 25% marrow blasts across both treatment groups for the Intent-to-Treat Analysis set

		0 - 1 Risk Factors			2 - 3 Risk Factors			4 - 5 Risk Factors
0%		5%	10%		15%	20%		2 %	30%

Axis Title

There was no difference between the dCR rates in patient groups across the risk factor categories (p=0.251).

Superior dCR Rate for Iomab-B versus CC

• In the crossover arm (N=44), 91% received transplant with 52.3% achieving CR/CRp.
• Six crossover patients (13.6%) achieved dCR of ≥ 180 days (95% CI [5.17,
  27.35]).
• Post-HCTmaintenance with TKI allowed only for Iomab-B patients with FLT-3 mutation or BCR-ABL translocation at baseline.
• CC patients received investigator's choice post-HCT maintenance therapy.

Conclusions

• Patients with R/R AML who have multiple risk factors are typically not considered for allogeneic HCT due to high transplant-related mortality and post-transplant relapse rates.
• 131I-apamistamab was effective in achieving durable responses in R/R AML patients irrespective of the presence of multiple high-risk factors such as adverse cytogenetics, age >65, venetoclax failure, high comorbidity index, or reduced

KPS, due to its targeted mechanism of action.

The SIERRA trial has completed enrollment (www.sierratrial.com or clinicaltrials.gov, NCT02665065)