Results of a phase 2 study of evorpacept (E, ALX148), cetuximab (C), and pembrolizumab (P) in patients with refractory
microsatellite stable metastatic colorectal cancer (MSS CRC)
Robert W. Lentz1, Patrick Blatchford1, Junxiao Hu2, Todd M. Pitts1, Adrie Van Bokhoven3, Hannah R. Robinson1, Nicole Balmaceda1, Emily Baiyee1, Alexis Leal1, Sunnie Kim1, S. Lindsey Davis1,Christopher H. Lieu1, Raymond Wadlow4, Kristen Spencer5, Aaron J. Scott6, Patrick M. Boland7, Howard S. Hochster7, & Wells A. Messersmith11. Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado. 2. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado. 3. Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado. 4. Inova Schar Cancer Institute, Fairfax, Virginia. 5. Division of Hematology & MedicalOncology, Department of Medicine, NYU Grossman School of Medicine, New York, New York. 6. Division of Hematology and Oncology, Department of Medicine, College of Medicine, The University of Arizona Cancer Center, Tucson, Arizona. 7. Division of Medical Oncology, Department of Medicine, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

BACKGROUNDBA

Legend:36-002
PI discre�on34-004

Subject ID

Evorpacept

METHODS• The safety-evaluable population included 16 patients (Figure 1), of whom 69% were male and median age
53 years. The primary tumor was in the right, left, and transverse colorectum in 31%, 31%, and 6% ofpatients, and was unknown in 31%. Mutations in KRAS, NRAS, and BRAF genes were present in 38%,6%, and 0% of patients. The median number of prior lines of therapy was 3, including prior EGFR
inhibitor in 44% (Table 1).
• In Stage 1, 9 and 3 patients were treated at E DL1 and DL-1, respectively. E DL1 was established as theRD for Stage 2, in which 4 patients were treated (Figure 1).
• The most common any-grade treatment-emergent adverse events were headache (38%), fatigue (31%),
acneiform rash (31%), anemia (25%), diarrhea (25%), and 19% each of dyspnea, abdominal pain,anorexia, nausea, vomiting, and hypomagnesemia (Table 2).
• There were two on-study deaths assessed as related to all three study drugs (hemophagocytic
lymphohistiocytosis and cytokine release syndrome; 1 each). While both are known associations withcheckpoint inhibitors, other significant factors contributing to these event outcomes included cancer
progression with high tumor burden in the former and patient decision to transition to comfort care in thelatter.
• In the safety-evaluable population, ORR was 6.3% (1 ongoing partial response, 95% confidence interval[CI] 0.2-30.2%), disease control rate was 12.5% (95% CI 1.6-38.3%), median progression-free survival
was 2.3 months (mo; 95% CI 1.9-2.7 mo), and median overall survival was 10.9 mo (95% CI 3.3 moinfinity). Formal hypothesis testing was not performed (Table 3, Figures 2 & 3).
CONCLUSIONS

Further dose optimization of ECP is needed to establish a RD in therefractory MSS CRC population. While initial activity was seen, at
the DLs evaluated, criteria to terminate study accrual were met.

Disease progression32-003

Disease prog-36-001

Disease progression

32-006

Disease progression

30-005

Disease progression

30-001

Disease progression

30-002

ressionStudy pause
PI discre�on34-001

Study34-003

Study pausepause

30-003Death

32-001Consent withdrawn

36-004Death

02

Discon�nua�on reason for each subject
is displayed at the end of the bar.

4681012Months On Study
Evorpacept Starting Dose Level:10 mg/kg

15 mg/kg

Figure 2: (A) Waterfall plot of best percent change in aggregate size of target lesions and (B) swimmer plotof duration of response, both by subject. In the safety-evaluable population. Patient 36-002: left-sided primary tumor,

Figure 1: CONSORT diagram.
Characteristic(N=16 Patients)
Sex

Primary Tumor Site

KRAS
NRAS
BRAF
Tumor Mutational
Burden (Muts/Mb)
Liver Metastases
Prior EGFR Inhibitor

Age (years)
Prior Lines of Therapy

Level

N (%)

FemaleMaleRight
Left
Transverse
Unknown
Wild-type
MutantUnknown
Wild-type
MutantUnknown
Wild-type
MutantUnknown< 10

5 (31)
11 (69)5 (31)
5 (31)
1 (6)
5 (31)
9 (56)
6 (38)1 (6)
13 (81)1 (6)
2 (13)
10 (63)06 (38)9 (56)≥ 10
Unknown
PresentPrior
NeverYes
No0
7 (44)
13 (81)1 (6)
2 (13)
7 (44)
9 (56)-Table 1: Baseline characteristics.

Median (IQR)
53 (44-68)
3 (2-4)Adverse Event(N=16 Patients)
Headache
Fatigue
Acneiform rash
AnemiaDiarrhea
Dyspnea
Abdominal pain
Anorexia
NauseaVomiting
Hypomagnesemia

Gr 1-2 Gr 3-4 Total
N (%) N (%) N (%)
5 (31)
5 (31)
5 (31)
3 (19)
4 (25)
1 (6)
2 (13)
3 (19)
3 (19)
3 (19)
3 (19)

1 (6)
00
1 (6)
02 (13)
1 (6)
00
0
0

6 (38)
5 (31)
5 (31)
4 (25)
4 (25)
3 (19)
3 (19)
3 (19)
3 (19)
3 (19)
3 (19)RAS/BRAF wild-type, prior EGFR inhibitor, and lung-only metastatic disease at study entry (prior liver metastasis s/p ablation);
remains on study as of 03/18/2024.

A

Number of Subjects At Risk for Progression:
112
16

2

Complete Response (CR)
Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)

01 (6.3)
1 (6.3)14 (87.5)

Objective Response Rate (ORR)
Disease Control Rate (DCR, PR + SD)

1 (6.3)2 (12.5)

Table 3: Best overall response by RECIST v1.1.

In the safety-evaluable population, defined as allpatients who received at least one dose of study drug(s).

B

0.8

Pr{Subject is Progression-Free} = 0.50

0.4

10

Median OS: 10.9 mo(95% CI 3.3 mo-infinity)

0.7
0.6
Pr{Subject is Alive} = 0.50

0.5
0.4

0.3

0.3

0.2

0.2
0.1

Median PFS

1Censored Subject

0.8

0.6

0.1

5

0.9

0.7

0.5

Number of Subjects At Risk for Death:16106
1.0Median PFS: 2.3 mo(95% CI 1.9-2.7 mo)Median OS

0.0

0.002.3

46

Months-to-Progression (or Censored)

N (%)

0Censored Subject

0.9

Table 2: Most common treatment-emergent
adverse events at the patient level.
Best Overall Response(N=16 Patients)1

1.0

Probability of Being Progression-Free

RESULTS32-00534-005This phase 2, single-arm, two-stage, multicenter, investigator-initiated trial of E (15 or 10 mg/kg weekly atdose level [DL] 1 and -1, respectively), C (400 mg/m2 then 250 mg/m2 weekly), and P (200 mg every 3weeks) in 21-day cycles enrolled patients with MSS CRC, regardless of tumor sidedness and RAS/BRAFstatus, refractory to ≥ 2 prior lines of therapy, including EGFR inhibitor if indicated (NCT05167409). All
patients in both Stage 1 (safety run-in) and Stage 2 (expansion) received ECP until progression orunacceptable toxicity. The co-primary objectives were to determine the recommended dose (RD) of E with
CP and objective response rate (ORR) by RECIST v1.1 (by one-sided exact test with α=0.05, H0 p ≤ 3%
[historical controls], HA p ≥ 15%; power is 87% with N=48).

Subject DiedPRSDDisease progression

32-004

Probability of Survival

Single-agent anti-PD-1/PD-L1 drugs are ineffective in MSS CRC. E is an engineeredprotein (high-affinity CD47-blocker fused to an inactive IgG Fc region), which blocks
the CD47/SIRPα innate immune inhibitory phagocytosis checkpoint expressed on
CRC and phagocytes, respectively. Preclinical evidence suggests ECP may beeffective in MSS CRC.

RESULTS

810036910.9 121518

Months-to-Death (or Censored)

Figure 3: Kaplan-Meier Curves for Progression-Free Survival (A) and Overall Survival (B). In the safety-evaluable population.

ADDITIONAL INFORMATION••••For questions or comments: Robert.Lentz@CUAnschutz.edu
Date of data extraction (updated from abstract): 03/18/2024
Clinical trial identifier: NCT05167409
Funding source: ALX Oncology Inc., Eli Lilly USA, Merck & Co, Inc, ASCO Young Investigator Award (to RWL), NIH
5K12CA086913-21 (to RWL), and NIH T32CA236734 (to RWL).
• Acknowledgements: The authors acknowledge Criterium, Inc., dba Academic Gastrointestinal Cancer Consortium (AGICC) forclinical trial support services, all participating sites and patients, the University of Colorado Cancer Center support Grant (NIHP30CA046934), the University of Colorado Pathology Shared Resource, and pharmaceutical sponsors.
• References: Lentz RW et al, GI ASCO Abstract/Poster, 2023. Kauder SE et al, PLoS One, 2018, Lakhani NJ et al, Lancet Oncol,
2021. ALX Oncology, Inc.