ASH 2023 Oral Presentation: Iomab-B Improves Survival in Patients with R/R AML and TP53 Mutation

131I-apamistamab-Led Allogeneic Hematopoietic Cell Transplant Significantly Improves Overall Survival in Patients with TP53 Mutated R/R AML

Hannah Choe, MD, Ben K. Tomlinson, MD, Boglarka Gyurkocza, MD, Rajneesh Nath, MD, Stuart Seropian, MD, Mark R. Litzow, MD, Camille N. Abboud, MD, Patrick J. Stiff, MD, Sunil Abhyankar, MD, James Foran, MD, Sameem Abedin, MD, George Chen, MD, Zaid Al-Kadhimi, MD, Partow Kebriaei, MD, Mitchell Sabloff, MSc, MD, FRCPC, Johnnie J. Orozco, MD, PhD, Katarzyna Joanna Jamieson, MD, Margarida Magalhaes- Silverman, MD, Koen Van Besien, MD, PhD, Michael W. Schuster, MD, Arjun D. Law, MD, Sebastian A. Mayer, MD, Hillard M. Lazarus, MD, Jennifer Spross, MA, Kate L Li, PhD, Elaina Haeuber, MS, Madhuri Vusirikala, MD, Akash Nahar, MD, MPH, Brenda M. Sandmaier, MD, John M. Pagel, MD, PhD, Sergio A. Giralt, MD, Avinash Desai, MD and Nebu Koshy, MD.

Background

• Patients with TP53 mutated R/R AML have a dismal prognosis with limited treatment options and are seldom offered alloHCT due to high post-transplant relapse rates.
• 131I-apamistamab(Iomab-B) is an anti-CD45 radioimmunoconjugate designed to deliver high dose targeted radiation to hematopoietic cells, allowing for myeloablation and eradication of leukemic cells to enable alloHCT in patients with active R/R AML while limiting off-target toxicity and being mutation- agnostic
• The SIERRA trial compared Iomab-B followed by alloHCT to physician's choice of conventional care, recently reporting that the study met its primary endpoint of durable complete remission lasting at least 6 months
• We compared the outcomes and safety data in patients enrolled in the SIERRA trial with a documented TP53 mutation versus wildtype

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SIERRA - A Phase 3 Randomized Trial in R/R AML

Total Accrual: N=153

Active, Relapsed
or Refractory		RANDOMIZED 1:1
AML

Key Eligibility Criteria:

• R/R AML ≥55 years of age with active disease (BM blast count ≥5% or the presence of circulating blasts)
• Karnofsky score ≥70
• 8/8 allele-level, related or unrelated matched donor
• Previous HCT were excluded

Iomab-B

HCT

Crossover*

*Control arm subjects

with no CR offered

crossover

Conventional Care**

**Wide range of flexible options at physician's discretion

No CR

CR

No CR or

MLFS

CR or

MLFS

		Endpoints:
		Pre-Specified Primary:
dCR		dCR = CR/CRp lasting
		≥180 days post-CR
		Secondary: OS and EFS

Standard of Care

Physician's Choice

HCT		dCR

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Personalized Single Dose Combined Induction/Conditioning

Dosimetric Dose		Therapeutic Dose
≤20 mCi		• Upper limit of 24 Gy to liver
		• Median 16 Gy to marrow

-19-18

-15

-12

Imaging

	RIC
FLU			TBI
30 mg/m2/d			200 cGy
			HCT

-4-3-2-1 0

Tac/CSA + MMF

RIC: reduced intensity conditioning; FLU: fludarabine; TBI: total body irradiation; HCT: hematopoietic cell transplant;

Tac/CSA: tacrolimus/cyclosporine; MMF: mycophenolate mofetil

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SIERRA Patient Distribution

153 Pts Randomized

Iomab-B

N=76

Conventional Care

N=77

• 4 pts did not receive dosimetric dose
• 6 pts did not proceed to therapeutic dose with
  HCT
  • TP53+: 33.3% (2 / 6)

1 pt did not

receive treatment

(TP53+)

No CR/CRp/MLFS

Achieved

CR/CRp/MLFS

66 patients received			Crossover to Iomab-B
therapeutic dose				N=44
	4 pts did not proceed to
	therapeutic dose with HCT
	TP53+: 50% (2 / 4)

HCT

N=66

TP53+: 22.7%

(15 / 66)

HCT

N=40

TP53+: 20%

(8 / 40)

No Further Treatment

N=18

TP53+: 44.4%

(8 / 18)

Conventional HCT

N=14

TP53+: 7.1%

(1 / 14)

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Baseline Characteristics in Patients with TP53 Mutations (N = 37)

	Iomab-B (N=17)	Conventional (N=10)	Crossover (N=10)
Age, years	63 (56-74)	66 (61-71)	64 (55-74)
Median (Range)
Pts >65 yrs: 6 (35.3)	Pts >65 yrs: 7 (70.0)	Pts >65 yrs: 4 (40.0)
N (%)
Disease Status at	Primary Induction Failure: 12 (70.6)	Primary Induction Failure: 7 (70.0)	Primary Induction Failure: 4 (40.0)
First Early Relapse: 4 (23.5)	First Early Relapse: 2 (20.0)
Randomization	First Early Relapse: 5 (50.0)
Relapse/Refractory: 0 (0.0)	Relapse/Refractory: 1 (10.0)
N (%)	Relapse/Refractory: 0 (0.0)
2nd + Relapse: 1 (5.9)	2nd + Relapse: 0 (0.0)
	2nd + Relapse: 1 (10.0)
Prior Lines of
Treatment	2 (1-4)	3 (1-4)	4 (1-6)
Median (Range)
Prior Venetoclax
Treatment	9 (52.9.)	6 (60.0)	6 (60.0)
N (%)
Karnofsky	≥90: 9 (52.9)	≥90: 1 (10.0)	≥90: 5 (50.0)
Performance Status
<90: 8 (47.1)	<90: 9 (90.0)	<90: 5 (50.0)
N (%)
HCT Co-Morbidity	0-2:9 (52.94)	0-2:6 (60.0)	0-2:6 (60.0)
Index
≥3: 8 (47.05)	≥3: 4 (40.0)	≥3: 4 (40.0)
N (%)

1. Per NCCN Guidelines, Version 3, 2020

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CR and dCR by TP53 Mutation Status and Treatment Received

• Overall dCR Rates at 6 months were 22% in the Iomab-B group vs. 0% in the CC group (95% CI;12.29, 34.73; p<0.0001), irrespective of TP53 mutational status.
• Median OS of TP53 positive patients on CC arm was 1.66 mos versus 5.49 mos in TP53 positive patients who received Iomab-B and alloHCT

		Iomab-B + Crossover		Conventional Care
	N		%	95% CI	N		%		95% CI
TP53 Positive	N = 27				N = 10
CR	15		55.56	(35.33, 74.52)	0		0		-
Durable CR	4		14.81	(4.19, 33.73)	0		0		-
TP53 Wildtype	N = 93		%	95% CI	N = 23		%		95% CI
CR	54		58.06	(47.38, 68.22)	4		17.39		(4.95, 38.78)
Durable CR	15		16.13	(9.32, 25.20)	0		0		-

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Survival Probability (%)

Improved Survival with 131I-apamistamab in Patients with TP53 Mutation

		Iomab-B +	Conventional
		Crossover	Care
		N = 27	N = 10
Iomab-B +	Median OS (mos)	5.49	1.66
(95% CI)	(3.94, 8.25)	(0.99, 2.96)
Crossover
CC	Hazard Ratio		0.23
	(95% CI)	(0.10, 0.52)
	p value (log-rank)		0.0002

Overall Survival (Months)

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SIERRA Trial Patients with TP53 Mutation

Treatment-Emergent Adverse Events (Grade ≥3)

	TP53 Positive Patients	TP53 Negative Patients
	Receiving Iomab-B +	Standard HCT
	Receiving Iomab-B + HCT1
	HCT1
		N = 14
		N = 83
	N = 23
Febrile
Neutropenia	11 (47.8)	35 (42.2)	7 (50.0)
N (%)
Mucositis2	4 ( 17.4)	13 (15.7)	3 (21.4)
N (%)
Sepsis	4 (17.4)	8 (9.6)	4 (28.6)
N (%)
Cumulative
Incidence	8.7 (1.4, 24.7)	8.6 (3.8, 16.1)	14.3 (2.1 , 37.6)
aGVHD (Gr III-IV)

% (95% CI)

• TP53 mutations are not associated with increased transplant-related toxicity

• Safety data in TP53 positive patients transplanted with Iomab-B aligns that of the entire Iomab-B-treated population

1. Includes patients randomized to Iomab-B arm and CC patients who crossed over to Iomab-B

2. 'Mucositis' includes the Preferred Terms 'Stomatitis' and 'Mucosal Inflammation'

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