A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia Open Access

In 1982, chronic myelomonocytic leukemia (CMML) was designated as a subtype of myelodysplastic syndrome (MDS).¹ Subsequent classification systems described this entity as a myelodysplastic/myeloproliferative overlap condition.² CMML is characterized by increased monocytes in circulating blood and has a unique molecular profile.^3,4 Acute myeloid leukemia (AML) has 8 recognized morphologic subtypes (M0-M7), of which M4 and M5 are characterized by blasts with myelomonocytic or monocytic differentiation.⁵ These M4 and M5 AML subtypes can occur de novo or as the result of progression of antecedent CMML.

Although hypomethylating agents (HMAs) such as azacitidine (AZA) and decitabine are approved for most MDS subtypes, including CMML, outcomes for patients with CMML with these therapies are poor, with a response rate of <50%.⁶ There are no specific therapeutic recommendations for CMML or AML with monocytic features. Incorporation of the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) has led to significantly improved clinical outcomes for many patients with myeloid malignancies. However, patients with AML with monocytic features do not respond as well to VEN-based therapies, with a median overall survival (OS) of only 89 days in newly diagnosed unfit patients with M5 AML treated with VEN + AZA, compared to 518 days for non-M5 AML.⁷ Incorporation of VEN into CMML regimens may not improve OS.^7-9 Therapeutic strategies to specifically target the unique features of CMML and AML with monocytic differentiation are necessary.

Leukocyte immunoglobulin–like receptor B4 (LILRB4) is an immune receptor with expression restricted to monocytic cells, with a significantly higher expression of LILRB4 on neoplastic monocytic AML and CMML cells than on normal monocytes.^10-12 LILRB4 is also expressed by monocyte precursors including monoblasts and promonocytes.¹¹ Expression on monocytic leukemic stem cells has also been suggested.^10,13 LILRB4-positive monocytic AML cells are associated with resistance to VEN and/or VEN + AZA.^7,14,15 

IO-202 is a first-in-class immunoglobulin G1 monoclonal antibody with specific, high-affinity binding to LILRB4, leading to depletion of LILRB4-positive cells via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Given the strong preclinical evidence that targeting LILRB4 may provide an effective targeted therapy specifically for monocytic neoplasms, we designed a phase 1 clinical trial of IO-202, alone and in combination with AZA ± VEN, for patients with monocytic leukemias (M4 and M5 AML) and high-risk CMML. Early trial results demonstrated promising efficacy in patients with CMML, leading to enrollment in an expansion cohort with IO-202 in combination with AZA specific to this rare disease.

This was a multicenter, nonrandomized, first-in-human phase 1a dose-escalation and 1b dose-expansion study to assess the safety and efficacy of IO-202, alone and in combination with AZA ± VEN, in patients with relapsed/refractory (R/R) AML with monocytic differentiation and in patients with R/R CMML or HMA-naïve CMML.

Eligible patients were ≥18 years of age, with an Eastern Cooperative Oncology Group score of 0 to 2, adequate organ function, and a confirmed diagnosis of myelomonocytic or monocytic/monoblastic AML or CMML. Monocytic disease was determined at local laboratories by standard hematopathologic assessments. Systemic immunosuppression or clinically significant graft-versus-host disease was exclusionary. Full eligibility criteria are listed in the ClinicalTrials.gov registry (NCT04372433).¹⁶ All patients provided informed consent according to the Declaration of Helsinki and local institutional guidelines.

IO-202 was investigated in 2 segments during this phase 1 study: part 1 (or phase 1a dose escalation) and part 2 (or phase 1b dose expansion; supplemental Figure 1). In part 1A, IO-202 was administered as monotherapy at escalating dose levels ranging from 0.03 mg/kg to 60 mg/kg using a 3+3 design and as an intravenus (IV) infusion over 60 to 120 minutes on days 1 and 15 of a 28-day cycle. In part 1B, IO-202 was combined with AZA, starting at 4.5 mg/kg while remaining 1 dose level below the safety-cleared dose in part 1A. AZA was administered at its approved dose and schedule of 75 mg/m² daily for 7 days by IV infusion or subcutaneous injection every 28 days and before IO-202 on day 1 of each cycle. For guidance on dose modifications of AZA, please see the VIDAZA prescribing information.¹⁷ 

Part 2 evaluated IO-202 at the recommended phase 2 dose, which consists of a loading dose of 60 mg/kg on day 1 followed by 30 mg/kg every other week (Q2W) starting from day 15, in 3 planned expansion cohorts: part 2A of IO-202 + AZA for LILRB4^high R/R monocytic AML; part 2B of IO-202 + AZA for HMA-naïve CMML; and part 2C of IO-202 + AZA + VEN for LILRB4^high newly diagnosed unfit AML. Part 2B was prioritized due to promising activity and no restriction on LILRB4 expression level. Part 2A had limited enrollment due to the requirement for patient selection based on LILRB4 expression, and part 2C did not open for enrollment.

All patients treated at a dose of ≥1.0 mg/kg must be premedicated before administering IO-202. It is recommended that premedication include an antihistamine (eg, diphenhydramine 25-50 mg IV) and an H2 blocker (eg, famotidine 20 mg IV or equivalent), administered ∼30 minutes before infusion.

Hydroxyurea was allowed for initial disease control in cycle 1. Hydroxyurea may be used during subsequent cycles if deemed necessary by the investigator. Systemic immunosuppressive medications exceeding 10 mg of prednisone or equivalent and other neoplastic therapies were prohibited.

Safety, tolerability, pharmacokinetics (PK), immunogenicity, efficacy, and pharmacodynamic biomarkers were assessed.

For PK analysis, serum samples were collected at multiple time points after the first dose during cycle 1, at preinfusion and end-of-infusion time points in select dosing cycles, at the end of treatment, and ∼30 days after the final dose. Serum IO-202 concentrations were measured using a validated enzyme-linked immunosorbent assay with low limit of quantification at 5 ng/mL. Preliminary PK analyses used non-compartmental methods with nominal dosing and sampling times, performed in Phoenix WinNonlin v8.4 (Certara).

For immunogenicity analysis, serum samples were collected at baseline and multiple predose time points during treatment, at the end of treatment, and ∼30 days after the final dose to assess anti-drug antibody (ADA) against IO-202. Testing used validated assays and a tiered strategy: initial screening followed by confirmation of positive results. The screening assay, optimized to tolerate drug interference, detected 25 ng/mL of positive ADA control in the presence of up to 300 μg/mL of IO-202.

LILRB4 expression was analyzed in a central laboratory by flow cytometry using bone marrow (BM) and peripheral blood samples with an anti-LILRB4 monoclonal antibody that is specific to LILRB4 but not competing with IO-202 for LILRB4 binding (clone ZM3.8; BD Biosciences). For parts 2A and 2C only, a prescreening evaluation of LILRB4 level analyzed at a central laboratory was required. Eligibility for parts 2A and 2C of LILRB4^high required >80% of blasts expressing LILRB4 and ≥5000 copies per blast in peripheral blood. If no blasts were detected in peripheral blood, assessment was performed in BM.

Adverse events (AEs) were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. AML responses were defined according to the European LeukemiaNet guidelines.¹⁸ The 2015 International Working Group myelodysplastic/myeloproliferative neoplasms (MDS/MPN) response criteria were used for patients with CMML.¹⁹ Objective responses for CMML include complete response (CR), marrow response (MR), partial remission (PR), and clinical benefit (CB). The overall response rate (ORR) is defined as the number of patients with objective responses divided by the number of efficacy-evaluable patients. Descriptive statistics were used for clinical and laboratory variables.

The safety population included all patients who received at least 1 infusion of IO-202 (N = 69). The efficacy-evaluable subset included patients with at least 1 response assessment (n = 66). The data cutoff date for both safety and efficacy was 28 October 2024.

Duration of response was calculated based on the time interval between the first response date and the documented date of either disease progression or allogeneic hematopoietic cell transplantation (allo-HCT) or the data cutoff date (for responders with ongoing treatment).

Part 1 was a dose-escalation study that enrolled a total of 46 patients with R/R AML and R/R CMML. Of these, 31 patients received IO-202 monotherapy in part 1A (26 with R/R AML and 5 with R/R CMML) and 15 received IO-202 in combination with AZA in part 1B (10 with R/R AML and 5 with R/R CMML; supplemental Figure 1).

Part 2A was a dose-expansion study of IO-202 + AZA for patients with LILRB4^high R/R AML (supplemental Figure 1). Two patients were enrolled.

Baseline characteristics and gene mutation frequencies from the total of 48 patients with R/R AML and R/R CMML are presented in supplemental Table 1 and supplemental Figure 2A-B, respectively.

IO-202 was well tolerated both as monotherapy and in combination with AZA (supplemental Table 2). No dose-limiting toxicities was observed. The maximum tolerated dose was not reached. The maximum administrated dose was 60 mg/kg Q2W IV. Treatmentemergent AEs (TEAEs) were reported in 100% patients, and treatment-related AEs (TRAEs) occurred in 47.9% of patients. TRAEs occurring in ≥10% of patients included nausea, fatigue, and vomiting based on System Organ Class/Preferred Term.

In part 1A (IO-202 monotherapy), 3 patients experienced grade ≥3 TRAEs, and 4 patients had serious AEs (SAEs), leading to withdrawal in 3 patients with symptoms including hallucination, acute respiratory distress syndrome, and chest pain. In parts 1B and 2A (IO-202 + AZA combination), all grade ≥3 TRAEs and SAEs were attributed to AZA alone or a combination of IO-202 and AZA, per investigators’ assessments.

Preliminary PK and immunogenicity analyses were conducted for 46 patients in part 1. IO-202 serum concentration vs time profiles after the first dose of cycle 1 are presented in supplemental Figure 3. Exposure, measured by the area under the concentration–time curve (AUC) from time 0 to the last measurable concentration, increased in a non–dose-proportional manner at lower doses, with a trend toward dose proportionality at higher doses (>4.5 mg/kg). At the 60 mg/kg dose level, the estimated clearance and half-life (t_1/2) were 9.63 mL/day/kg and 7.59 days, respectively. Minimal to no accumulation of IO-202 was observed with Q2W dosing, supporting the use of this regimen. Because of the small sample size, we could not fully evaluate how AZA affects IO-202 PK. Nevertheless, dose-normalized AUC values at 30 and 60 mg/kg were within a twofold range between monotherapy (836-695 [day∗μg/mL]/[mg/kg]) and combination therapy (630-480 [day∗μg/mL]/[mg/kg]), suggesting that AZA may have little impact on IO-202 PK.

Overall, the incidence of ADAs was 15.6% and observed in cohorts with low doses of IO-202 (0.1 mg/kg to 1.5 mg/kg). The impact of ADAs on PK profile was not conclusive due to high variations of IO-202 PK exposures at low dose levels.

Preliminary efficacy was assessed in the 48 enrolled patients and is summarized in supplemental Table 3. In part 1A, IO-202 monotherapy efficacy was observed in 1 patient with R/R AML and 1 patient with R/R CMML, whereas most patients were treated at low dose levels. In part 1B, among 10 patients with R/R AML treated with IO-202 in combination with AZA, 1 achieved CR and remained on study for >14 months. Among 5 patients with R/R CMML, the ORR was 60%. In part 2A, among 2 patients with LILRB4^high R/R AML enrolled, 1 achieved a morphologic leukemia-free state.

Additionally, analysis of LILRB4 expression in 46 patients from part 1 and its relationship with preliminary efficacy were conducted. The former is presented in supplemental Figure 4, and the latter is shown in supplemental Figure 5A-B.

Demographics and baseline characteristics of the 21 patients with HMA-naive CMML treated at the recommended phase 2 dose of IO-202 in combination with AZA are presented in Table 1, with individual patient data detailed in Table 2. The gene mutation frequencies are shown in supplemental Figure 2C.

The overall rates of TEAEs and TRAEs were 100% and 90.5%, respectively (Table 3). There were only 3 grade 3 TRAEs attributed to IO-202, as assessed by investigators: diarrhea, somnolence, and infusion-related reactions (IRRs). All cases resolved, with 2 recovered with supportive care measures. Additionally, there were 4 SAEs related to IO-202, as assessed by investigators: 3 IRRs (grade 2, n = 2; grade 3, n = 1) and 1 case of pyrexia (grade 2). All recovered with supportive care measures.

Efficacy-evaluable patients were defined as those who completed the first treatment cycle and had an end-of-cycle assessment. Of the 21 patients with HMA-naïve CMML enrolled in part 2B, 18 met these criteria and were included in the efficacy analysis. Based on the 2015 International Working Group MDS/MPN response criteria, the CR rate was 27.8% (5/18), and the ORR was 66.7% (12/18; Figure 1). In the subset of 6 patients with the highest LILRB4 expression (LILRB4-positive blasts >50% and >4500 copies per cell in BM), the CR rate was 33.3%, and the ORR was 100%.

Responses were rapid and durable (Figure 1). As of the data cutoff date, the median time to first response was 1 treatment cycle, and the median time to best response was 3 cycles. Among the 12 responders, the mean duration of response was 151 days (5.0 months), with a median of 102 days (3.4 months; range, 25-469 days; Table 4). Six patients remained on treatment. One patient continued therapy for >16 months. Five patients discontinued due to lack of response.

Seven of 18 efficacy-evaluable patients (38.9%) proceeded to allo-HCT (supplemental Table 4). These patients had a median age of 70 years (range, 61-74) and received a median of 5 treatment cycles (range, 3.5-12) of IO-202 + AZA before allo-HCT. Six of the 7 patients achieved a response before allo-HCT, including 3 CR, 2 MR, and 1 CB. The median interval between the last dose of IO-202 and allo-HCT was 35 days (range, 7-74).

Responses were consistently observed across diverse subgroups of patients with HMA-naïve CMML. Among the 12 patients with an objective response (5 CR, 2 MR, and 5 CB), 58.3% had proliferative disease, 58.3% had >5% blast counts, 66.7% had unfavorable ASXL1 genetic mutations, and 58.3% had high-risk CMML-specific Prognostic Scoring System that incorporates molecular genetic data (CPSS-Mol) score at baseline.

Treatment also led to several clinically meaningful improvements. All 18 efficacy-evaluable patients achieved or sustained a BM blast percentage <5% (7/18 patients were treated with hydroxyurea intermittently; Figure 2). Peripheral blood markers improved notably: 88% achieved monocyte counts ≤1 × 10⁹/L; and 93% had white blood cell counts ≤10 × 10⁹/L. Furthermore, among patients with baseline hemoglobin levels <11 g/dL, 7 of 16 (44%) achieved levels ≥11 g/dL without requiring red blood cell transfusions. Of 7 transfusion-dependent patients, 4 (57.1%) became transfusion independent. Of 6 patients with thrombocytopenia, 3 (50%) saw platelet counts improve to ≥100 × 10⁹/L with treatment.

A noteworthy finding was the rapid and substantial improvement in symptoms. All patients with baseline symptom scores >15 experienced a ≥50% reduction in their MPN-MSF TSS. Each of these changes was statistically significant. Although genetic profile data before and after treatment were limited, 3 patients had baseline KRAS mutation variant allele frequencies ranging from 2% to 41% and had posttreatment data available. All 3 patients demonstrated complete clearance of the KRAS mutant alleles on therapy.

LILRB4 expression in patients with HMA-naïve CMML is highly variable, with LILRB4-positive BM blasts ranging from 1.7% to 94.2%, and LILRB4 density ranging from 513 to 7762 copies of receptor per blast (Figure 3A).

Two distinct groups were identified based on the percentage of LILRB4 expression in BM blasts. Although mutations in ≥1 gene such as SRSF2, SETBP1, ZRSR2, TP53, and NF1 were detected among the 14 patients with >50% LILRB4 expression, no mutations were observed in these genes in the 7 patients with low percentage of LILRB4 expression. On the contrary, although mutations in EZH2 gene were detected among the 7 patients with low percentage of LILRB4 expression, no mutations were observed in this gene in the 14 patients with >50% LILRB4 expression. With limited sample size, the significance of these findings remains unknown.

Among patients with the highest LILRB4 expression (>50% LILRB4-positive blasts and >4500 copies per blast), all achieved a response (ORR, 6/6 [100%]), whereas patients with lower expression levels did not achieve the same rate of response (ORR, 6/11 [54.5%]; Figure 3B).

This is the first-in-human clinical trial that investigated IO-202, a humanized immunoglobulin G1 antibody with high affinity and specificity toward LILRB4, in patients with CMML and AML. Rapid and significant depletion of LILRB4-positive blasts have been observed, indicating strong target engagement and antibody effector function. IO-202 is, to our knowledge, the first anti-LILRB4 antibody under clinical development for HMA-naïve CMML, with potential applicability in other hematologic malignancies such as AML.

Overall, IO-202 has been shown to be safe and well tolerated both as monotherapy and in combination with AZA at doses up to 60 mg/kg Q2W. No dose-limiting toxicities have been reported. IRRs are a recognized risk associated with monoclonal antibodies and are considered as an identified risk for IO-202. To date, 9 of 69 enrolled patients (13.0%) treated with IO-202 have experienced IRRs. These included 2 patients in part 1A (3 cases in total, with each patient experiencing 1 SAE during the first infusion), 1 in part 1B, 1 in part 2A, and 5 in part 2B (including 3 SAEs during the first infusion). Most IRRs were grade 1 or 2 in severity, with only 1 grade 3 IRR reported in part 2B. Most IRRs occurred during the first dose of IO-202, and only 2 patients experienced a second IRR related to IO-202. They were resolved with treatment, including steroids, supportive care, and/or a slower infusion rate, without necessitating discontinuation or dose reduction of IO-202.

In patients with HMA-naïve CMML (part 2B), the combination therapy of IO-202 with AZA achieved a CR rate of 27.8% and ORR of 66.7%. Responses were evident across all subgroups. Specifically, 7 patients with proliferative disease responded to treatment. Similarly, 7 patients with baseline blast counts >5% achieved a response and 7 patients with high CPSS-Mol scoreshowed clinical response. Furthermore, 8 patients with ASXL1 mutations responded to the combination therapy. Additional benefits were also notable: 7 of 18 efficacy-evaluable patients (38.9%) were bridged to allo-HCT; 4 of 6 transfusion-dependent patients achieved transfusion independence; 3 of 6 patients with low platelets at baseline improved to the normal range; and all 7 patients with baseline MPN-SAF TSS >15 experienced a reduction of >50%. Furthermore, all 3 patients with available KRAS mutation data had elimination of KRAS mutant alleles. The presence of a RAS mutation is often associated with a poorer response to HMA.²⁰ Therefore, these data imply disease-modifying potential of IO-202.

LILRB4 expression on leukemic blasts in patients with CMML and AML was highly variable by flow cytometry (Figure 3; supplemental Figure 4). In vitro antibody-dependent cellular cytotoxicity results have demonstrated that depletion of LILRB4-positive cells by IO-202 is dependent on the density of LILRB4 (ie, copy number per cell). This suggests that patients with high LILRB4 expression may derive greater response. In patients with HMA-naïve CMML in part 2B (Figure 3B), all patients with the highest LILRB4 expression (>50% LILRB4 positive blasts and >4500 copies per blast in BM) achieved a response, suggesting that IO-202 contributed significantly to the observed efficacy. Because IO-202 + AZA was tested in patients with HMA-naïve CMML, AZA alone would be expected to show activity in some patients. As expected, 3 of 6 efficacy-evaluable patients with low LILRB4 expression still achieved a response. This effect could be primarily attributed to AZA alone; however, IO-202’s role in depleting LILRB4-positive blasts and abnormal monocytes in these patients cannot be excluded. Notably, the median time to first response was 1 cycle, and the median time to best response was 3 cycles. This is faster than the historical data for AZA monotherapy, in which the median time to first response is typically 2 to 4 months.^21-23 The rapid onset of action is consistent with IO-202’s mechanism of action.

The ASXL1 mutation, presented in ∼40% of patients with HMA-naïve CMML according to the literature,^4,24 was seen in 71.4% of patients in this study. Moreover, 45% were classified as high risk by CPSS-Mol score (Table 1).²⁵ These baseline imbalances highlight the difficulty in comparing outcomes with historical controls. Additionally, due to limited data, the prognostic value of LILRB4 expression in CMML remains unclear, although it has been linked to worse survival in AML and multiple myeloma.^7,26 

The revised 2022 World Health Organization and International Consensus Classification criteria for CMML lowered the threshold for absolute monocyte counts in peripheral blood from ≥1 × 10⁹/L to ≥0.5 × 10⁹/L, which is expected to increase the incidence by more than fivefold from annual incidence of 1100 cases.^27-30 In this study, no significant correlation was observed between monocyte counts in blood and LILRB4 expression levels on blasts in BM. Therefore, we anticipate that the revised classification criteria with expanded patient population will not affect the proportion of LILRB4-positive blasts or monocytes, and IO-202 could benefit the expanded CMML population by depleting LILRB4-positive leukemia blasts.

In conclusion, IO-202 is well tolerated and significantly reduces monocytic blasts and abnormal monocytes in HMA-naïve CMML, offering multiple meaningful benefits besides CR and ORR. Given the limited number of patients in this nonrandomized study, the observed activity of IO-202 should be considered preliminary and requires further validation. Nevertheless, as the first LILRB4 antibody evaluated in blood neoplasia, to our knowledge, IO-202 has demonstrated early signs of clinical potential, supporting its continued investigation in a randomized/pivotal study in HMA-naïve CMML.

The authors thank the patients, their families, and site personnel for participating in this study and the Leukemia and Lymphoma Society Therapy Acceleration Program for strategic support. The authors also thank Ying Zhu for ensuring investigational product supply, Roya Nawabi and Kristin Gibbons for managing clinical operations, Yasuhiro Tabata and Wen Hong Lin for medical monitoring, Donna Valencia for safety data management, Kyu Hong for bioanalysis support, Rong Deng for clinical pharmacology assistance, John Bergan for regulatory interactions, and Penny Dong for project and alliance management.

This study was funded by Immune-Onc Therapeutics, Inc., with additional support from the National Institutes of Health (NIH) Small Business Innovation Research grant (R44CA250543) and the California Institute for Regenerative Medicine (CIRM) grant (CLIN2-12149) to Immune-Onc Therapeutics, Inc.

The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or CIRM.

Contribution: C.D.D., D.A.P., and P.W. were the main contributors to the study design; and all authors contributed to the acquisition, analysis, and interpretation of study data, critically reviewed the manuscript, and provided final approval.

Conflict-of-interest disclosure: G.N.M. is a consultant for AbbVie and Menarini-Stemline; has served on scientific advisory committees for AbbVie, Astellas, Genentech, Immunogen, Menarini-Stemline, Orbital, Rigel, Servier, Syndax, Taiho, and Wugen; and has received research funding from Aptose, Astex, Blossom Hill, Bristol Myers Squibb (BMS)/Celgene, Daiichi Sankyo, GlycoMimetics, Immunogen, Jazz Pharmaceuticals, Menarini-Stemline, Taiho, and Syndax. Y.F.M. has received honoraria and consulting fees from BMS, Kura Oncology, Blueprint Medicines, Geron, OncLive, MD Education, Targeted Oncology, Curio Science, and Medscape Live; advisory board fees and honoraria from Stemline Therapeutics, Blueprint Medicines, Taiho Oncology, SOBI, Rigel Pharmaceuticals, Geron, Cogent Biosciences, and AbbVie; and travel reimbursement from MD Education. B.A.J. has received consultancy and advisory role fees from AbbVie, BMS, Daiichi Sankyo, Gilead, Kura, Rigel, Schrodinger, Syndax, and Treadwell; serves on the data monitoring committee for Gilead; and has received research funding to the institution from AbbVie, Amgen, Aptose, AROG, Biomea, BMS, Celgene, Forma, Forty Seven, Genentech/Roche, Gilead, GlycoMimetics, Hanmi, Jazz Pharmaceuticals, Kymera, Loxo, Pfizer, Pharmacyclics, and Treadwell. G.J.R. is a consultant for AbbVie, Amgen, AstraZeneca, BMS, Caribou Biosciences, Celgene, Daiichi Sankyo, Ellipses Pharma, Genoptix GlaxoSmithKline, Geron, GlycoMimetics, Janssen, Jasper Pharmaceuticals, Jazz Pharmaceuticals, Molecular Partners, MorphoSys, NeoGenomics, Novartis, OncoPrecision, OncoVerity, Pfizer, Rigel, Roche, and Syndax; and has received research support from Janssen. D.J. has received research funding from Jazz Pharmaceuticals and Pfizer. H.L. has served at advisory board meetings for Rigel and Incyte; and received consultation fees from AbbVie in the past 2 years. H.E.C. has served on advisory boards and as a consultant for Daiichi, Agios, AbbVie, BMS, Stemline, Jazz, Novartis, and Servier; has received research funding for an investigator-initiated study from Celgene; and has served DSMBs for ASTEX, Taiho, and Syndax. J.N.S. has received research funding from IKENA and is a consultant for Rigel. T.H., X.C.L., and H.X. are employees of Immune-Onc Therapeutics, Inc., P.W. is a former employee of Immune-Onc Therapeutics, Inc. B.K. is a paid consultant for Immune-Onc Therapeutics, Inc. D.A.P. has received research funding from Teva, Karyopharm, AbbVie, and BMS; and advisory board fees or honoraria from AbbVie, BMS, Gilead, Boehringer Ingelheim, Sanofi, Karyopharm, MEI, OncoVerity, Rigel, Syndax, Qihan, BeiGene, Ryvu, Servier, Taiho, and Astellas. C.D.D. has served on advisory boards or acted as a consultant for AbbVie, Astellas, AstraZeneca, BMS, Daiichi Sankyo, GlaxoSmithKline, Rigel, Schrodinger, and Servier. The remaining authors declare no competing financial interests.

Correspondence: Courtney D. DiNardo, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0428, Houston, TX 77030; email: cdinardo@mdanderson.org; and Hong Xiang, Immune-Onc Therapeutics, Inc, 795 San Santonio Rd, Palo Alto, CA 94303; email: hong.xiang@immuneonc.com.