A phase I investigator-initiated trial ofevorpacept (ALX148), lenalidomide andrituximab for patients with relapsed or refractory
B-cell non-Hodgkin lymphoma
Paolo Strati, Lei Feng, Dai Chihara, Jason Westin, Sairah Ahmed, Luis Fayad,
Jared Henderson, Jeffrey Davidson, Elizabeth McChesney, Loretta J Nastoupil,
Sattva S Neelapu, Christopher R Flowers
Department of Lymphoma and Myeloma, Biostatistics
The University of Texas MD Anderson Cancer Center
Houston, Texas, USA
AACR Abstract #10285

Disclosures
Research support: Sobi, Astrazeneca Acerta, ALX
Oncology, ADC Therapeutics, Kite-Gilead
Advisory Board/Consultancy: Kite Gilead, Hutchinson
Medipharma, ADC Therapeutics, TG Therapeutics, IncyteMorphosys, Astrazeneca Acerta, Sobi, Roche Genentech,
Abbvie-Genmab
Active grants: Leukemia Lymphoma Society, Kite-Gilead,
Sabin Family

MD Anderson

Department of Lymphoma/Myeloma

Lenalidomide and rituximab (R2) is active in patients withfollicular lymphoma (FL)
RELEVANCE trial(frontline)

AUGMENT trial(salvage)

Phase II trial at MDACC

Only CR associated with PFS
CR rate for R2 in relapsed FL only 34%

MD Anderson

Department of Lymphoma/Myeloma

Morschhauser F et al, JCO 2022
Leonard JP et al, JCO 2019
Strati P et al, Blood 2021

SIRPα-positive macrophages increase at time of progression after
R2 in patients with FL
CSF1-R+ SIRPα+ M before R2
CSF1-R+ SIRPα+ M

CD163+ SIRPα+ M

CSF1-R+ SIRPα+ M after R2

Marques-Piubelli M et al, Blood Adv 2022
MD Anderson

Department of Lymphoma/Myeloma

Evorpacept (ALX148) abrogates the ‘do-not-eat-me signal’ for
SIRPα+ macrophages without targeting red blood cellsHighaffinity

Courtesy of ALX Oncology
MD Anderson

Department of Lymphoma/Myeloma

Evorpacept increases antibody-dependent cellular phagocytosis
in combination with rituximab

Courtesy of ALX Oncology
MD Anderson

Department of Lymphoma/Myeloma

The combination of evorpacept and rituximab is well tolerated
and active in patients with relapsed B-NHL

Indolent B-NHL
10 mg/kg QW: 3 CR, 1 PR
15 mg/kg QW: 3 CR, 1 PR
Lakhani N et al, ASCO 2018
Kim TM et al, ASH 2019
MD Anderson

Department of Lymphoma/MyelomaHypothesis and Methods
We hypothesize that evorpacept and R2 will be synergize, and be safe andeffective for the treatment of pts with relapsed refractory B-NHL
Phase 1 single arm study (NCT05025800) conducted between 11/2021 and09/2023 (data cutoff 12/2023).
Adult pts with relapsed refractory B-NHL≥2 prior lines of systemic therapy (1 in case of indolent B-NHL); patientspreviously treated with lenalidomide excluded.
Evorpacept administered IV every 28 days x 12 cycles, at two dose levels:
30 mg/Kg on D1 and D15, or 60 mg/Kg on D1. Standard R2.
Dose limiting toxicity evaluated by CTCAE v5 during cycle 1, with a target
DLT rate of 0.3 (Bayesian Optimal Interval design).
Response was assessed by Lugano 2014 criteria.
MD Anderson

Department of Lymphoma/Myeloma

Treatment schema*(*) if PET CR, treatment
with ALX148 can be stopped
after 6 more cycles
Doselevel

ALX148 IV

Rituximab Lenalidomide
IV Q4W
PO DAILY(QW in C1)(D1-21)

Cohort -1

15 mg/Kg
QW
30 mg/Kg
Q2W
60 mg/Kg
Q4W

375 mg/m2

20 mg

375 mg/m2

20 mg

375 mg/m2

20 mg

Cohort 1
Cohort 2
MD Anderson

Department of Lymphoma/MyelomaBaseline characteristics
Patients (N=20)
AgeCaucasian
Male
Hemoglobin (g/dL)
β2-microglobulin (mg/L)
LDH (U/L)
Follicular lymphoma
Marginal zone lymphoma
Mantle cell lymphoma
Richter Syndrome
Grade 3A
Bone marrow, involved
B-symptoms, present
Ann Arbor Stage III-IV
Involved nodal areas (n)Largest lymph node (cm)
Extra-nodal disease, present
SUVmaxMD Anderson

Number (%);
Median [Range]
61 [27-85]
13 (65)10 (50)12.8 [9.2-15.2]
2.3 [0.8-6.2]
222 [129-338]
15 (75)
3 (15)
1 (5)
1 (5)3/15 (20)
4 (20)
3 (15)
18 (90)3 [1-5]
2.9 [1.5-5.6]
11 (55)15.8 [3.9-53.7]

Department of Lymphoma/Myeloma

Patients (N=20)
FLIPI score, lowIntermediate
high
FLIPI-2 score, lowIntermediate
high
PRIMA PI, lowIntermediatehighPrevious systemic therapies (n)Previous anti-CD20 antibody
Previous chemotherapy
Previous POD24

Number (%);
Median [Range]
3/18 (17)
6/18 (33)
9/18 (50)
4/18 (22)
10/18 (56)
4/18 (22)
13 (72)4 (22)1 (6)
1 [1-3]20 (100)
13 (72)16 (80)Dose adherence
Patients (N=20)
Cycles (n)Cycle delay
Lenalidomide dose reduction
Lenalidomide delay
Lenalidomide discontinuation
Evorpacept dose reduction
Evorpacept delay
Evorpacept discontinuation
Rituximab omission

Number (%); Median [Range]
12 [1-12]
8 (40)
6 (30)
12 (60)1 (5)0 (0)7 (38)1 (5)0 (0)Protocol modified to allow treatment with G1 LFT elevation
Delays mainly driven by R2-related complications
1 case of biopsy proven lenalidomide associated myocarditis
MD Anderson

Department of Lymphoma/Myeloma

Treatment-emergent adverse eventsPatients (N=20)
Neutropenia
Infections
ALT increased
Skin rash
AnemiaAST increase
ALP increased
Infusion-related reaction
Myocarditis

Grade 1-2
6 (30)
5 (23)
12 (60)8 (40)
12 (60)12 (60)4 (20)
6 (30)0 (0)Grade 3-4
11 (55)6 (30)
3 (15)
2 (10)
2 (10)
2 (10)
1 (5)
1 (5)
1 (5)

3 patients received DL1; 17 patients DL2
No DLT observed

MD Anderson

Department of Lymphoma/Myeloma

Patients (N=20)
Fatigue
Thrombocytopenia
Creatinine increase
Musculo-skeletal pain
Constipation
NauseaCOVID infectionHyponatremia
DiarrheaDizziness
Bilirubin increase
Peripheral neuropathy
HeadacheHypercalcemia
Xerostomia
Mucositis

Grade 1-2
13 (65)10 (50)10 (50)9 (45)
7 (35)
5 (25)
5 (25)
4 (20)
4 (20)
4 (20)
4 (20)
3 (15)
3 (15)
3 (15)
2 (10)
2 (10)

Grade 3-4
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)

Efficacy results: Response rates

Among the 18 patients with iNHL
ORR 94%, CR rate 83%

Evaluable patients
MD Anderson

201511(3 cycles)(6 cycles)(12 cycles)

Department of Lymphoma/Myeloma

Efficacy results: duration of response

1 Richter Syndrome (from CLL)
1 suspected transformation of FL

MD Anderson

Department of Lymphoma/Myeloma

Efficacy results: Progression-free and overall survival

Progression-free survival

N PD/dead 1-y PFS
20670%
No transformations
1-y PFS for iNHL: 72%

Overall survival

N dead 1-y OS
20 390%
2 deaths due to PD, 1 due to COVID19 (in CR)
1-y OS for iNHL: 94%… : 95% confidence intervalMedian follow-up 16 months (95% CI, 12-20 months)
MD Anderson

Department of Lymphoma/Myeloma

Conclusions and future directions

The addition of evorpacept (ALX-148) to R2 is a well tolerated salvage
regimen for patients with relapsed B-NHL
The combination results in high CR rates in patients with relapsed
refractory iNHL (historical 30%)
Bulk RNA-sequencing of pre-treatment and on-treatment (cycle 1) tissue
biopsies is ongoing
Phase 2 study at the RP2D (60 mg/Kg IV Q4W) for only 6 cycles is ongoingin patients with previously untreated iNHL (N=24)

MD Anderson

Department of Lymphoma/MyelomaAcknowledgments

Indolent Lymphoma
Loretta J Nastoupil
Christopher R Flowers
Sattva S Neelapu
Dai Chihara

Study coordinators
Jeffrey Davidson
Elizabeth McChesney

Lymphoma Department
Jason Westin
Sairah Ahmed
Luis E Fayad

Laboratory
Jared Henderson

Biostatistics
Lei Fang

All patients and families
ALX Oncology

Andrew Sabin
Family Award

Questions: pstrati@mdanderson.org
MD Anderson

Department of Lymphoma/Myeloma