emavusertib (CA-4948) / Curis, Dr. Reddy’s - LARVOL DELTA

Adding trastuzumab for HER+ status to a first-line regimen of emavusertib plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) and a PD-1 inhibitor (nivolumab or pembrolizumab) for metastatic or unresectable esophageal, GEJ, or gastric cancer has proven encouraging… (AJMC) - "At the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, new multifaceted analyses were presented....Among the 7 patients included in this analysis, 3 of whom initially received 150 mg and 4 of whom received 200 mg, there have been no dose-limiting toxicities. The expansion dose is the 200-mg dose of emavusertib....In the escalation phase, there has so far been 1 complete response, 1 partial response, and 1 case of stable disease in the patients receiving 150 mg; however, the patient who achieved the complete response did experience disease progression after 25 months."

P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

Phase I trial of emavusertib (CA-4948) in combination with FOLFOX/PD-1 inhibitor +/- trastuzumab for untreated, unresectable gastric and esophageal cancer. (ASCO-GI 2026) - P1 | " This is a single-institution, Phase I, dose escalation/expansion clinical trial of emavusertib in combination with FOLFOX and PD-1 inhibitor (nivolumab or pembrolizumab) and anti-Her2 therapy (trastuzumab if Her2 positive) as first-line therapy for metastatic or unresectable esophageal, gastroesophageal junction, or gastric cancers (adenocarcinoma or squamous cell carcinoma) (NCT05187182)... At this early stage of the study, emavusertib in combination with FOLFOX/ PD-1 inhibitor +/- trastuzumab as first-line therapy for metastatic or unresectable gastroesophageal cancers has a manageable toxicity profile and shows encouraging preliminary results. Enrollment in dose expansion arms at emavusertib 200mg BID (Her2 positive and negative) is ongoing."

Combination therapy • P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • IRAK4

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

TAKEAIM LEUKEMIA- A PHASE 1/2A STUDY OF THE IRAK4 INHIBITOR EMAVUSERTIB (CA-4948) AS MONOTHERAPY OR IN COMBINATION WITH AZACITIDINE OR VENETOCLAX IN RELAPSED/REFRACTORY AML OR MDS (EHA 2022) - P1/2 | "No dose-limiting myelosuppression was reported, suggesting emavusertib may be a candidate for combination therapy. Accrual of Phases 1b and 2a is ongoing."

Combination therapy • Monotherapy • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Immunology • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • IRAK4 • SF3B1 • U2AF1

Phase 1/2a study of the IRAK4 inhibitor CA-4948 as monotherapy or in combination with azacitidine or venetoclax in patients with relapsed/refractory (R/R) acute myeloid leukemia or lyelodysplastic syndrome. (ASCO 2022) - P1/2 | "CA-4948 is well tolerated and effective in heavily pretreated AML and HR-MDS patients, especially in those with U2AF1/SF3B1/FLT3 mutations. No dose-limiting myelosuppression was reported, suggesting CA-4948 may be a candidate for combination therapy. Accrual of Phases 1b and 2a is ongoing."

Clinical • Combination therapy • Monotherapy • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Immunology • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • IRAK4 • SF3B1 • U2AF1

Takeaim Lymphoma: An Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Combination with Ibrutinib in Patients with Relapsed or Refractory Hematologic Malignancies (ASH 2023) - P1/2 | "The combination of emavusertib plus ibrutinib (ema+ibr) is well tolerated with an acceptable long-term safety profile and promising efficacy, showing several objective responses in heavily pretreated and/or BTK inhibitor resistant patients. Emavusertib may have the potential to overcome BTK inhibitor resistance and the combination of ema+ibr has the potential to show increased anti-cancer activity compared to ibrutinib monotherapy."

Clinical • Combination therapy • Chronic Lymphocytic Leukemia • CNS Lymphoma • Dental Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Stomatitis • FLT3 • IL1R1 • IRAK4 • MYD88

Preliminary Safety, Efficacy, and Molecular Characterization of Emavusertib (CA-4948) in Relapsed/Refractory Acute Myeloid Leukemia Patients (ASH 2024) - P1/2 | "Patients with relapsed/refractory (R/R) AML who have failed standard therapies, including venetoclax (VEN), hypomethylating agents (HMA), and/or FLT3 inhibitors (FLT3i) have limited therapeutic options. Enrollment in this trial is ongoing at 300 mg BID in patients with < 3 lines of prior anti-cancer therapies. Combination trials across the emavusertib program are ongoing with HMA, BCL2 and BTK-inhibitors."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • BCL2 • BCOR • FLT3 • IRAK4 • NRAS • RUNX1 • SF3B1 • SRSF2 • U2AF1 • WT1

Development of HPB-092: A novel dual kinase inhibitor targeting FLT3 and IRAK4 for the treatment of relapsed/refractory Acute Myeloid Leukemia (RR-AML) (ASH 2025) - "Compared to the approved FLT3 inhibitors gilteritinib and quizartinib, as well as the clinical-stage dual inhibitor CA-4948, HPB-092 displayed comparable or superior potency against mutant FLT3 and IRAK4, improved kinome selectivity (selectivity score 50 μM), and no hERG inhibition (IC50 > 10 μM), along with an excellent overall safety profile in nonclinical species. The study has been approved by the Institutional Review Board (IRB) and has also been submitted to ClinicalTrials.gov, currently pending final approval. The first patient is anticipated to be enrolled in the fourth quarter of 2025."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • IRAK4 • SF3B1 • U2AF1

Preliminary pharmacokinetic and MRD results from AML patients treated with 7- and 14-day dosing schedule of emavusertib added to combination therapy with azacitidine and venetoclax (ASH 2025) - "Optimization of dosing regimens in triplet combination continue to be investigated. Theseinitial findings support further investigation of the addition of emavusertib to this regimen in order toimprove patient outcomes in a hard-to-treat population."

Clinical • Combination therapy • PK/PD data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • IRAK4

CA-4948 in Combination With Cisplatin, Gemcitabine, and Durvalumab in Patients With Untreated Advanced or Metastatic Biliary Tract Cancer (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2031 ➔ Apr 2032 | Initiation date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Jan 2030 ➔ May 2030

Trial completion date • Trial initiation date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

A Study of Emavusertib + An Approved Bruton Tyrosine Kinase Inhibitor (BTKi) in Participants With Chronic Lymphocytic Leukemia (CLL) and Other B-cell Malignancies (clinicaltrials.gov) - P2 | N=108 | Not yet recruiting | Sponsor: Curis, Inc.

New P2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Curis Provides Updated Data from its Frontline AML Triplet Study (PRNewswire) - "The AML triplet study is evaluating the addition of emavusertib (ema) to the combination of venetoclax and azacitidine (ven-aza) in AML patients who have achieved complete remission on ven-aza but remain MRD-positive (MRD+), with the goal of enabling patients to achieve uMRD....In the ASH abstract, the company reported initial data showing 4 of 8 patients (50%) had achieved uMRD as of July 2, 2025. These data were updated in the poster presented at ASH with 5 of 8 patients (62.5%) achieving uMRD, with no change in safety profile, as of October 12, 2025."

P1 data • Acute Myelogenous Leukemia

Targeting myddosome signaling to improve immunotherapy in melanoma brain metastases (SNO 2025) - P1/2 | "Targeted IRAK-4 inhibition with emavusertib reprograms suppressive TAMs and enhances response to anti-PD-1 therapy in MBM models. These findings support emavusertib as a promising adjuvant to ICB in MM, providing the foundation for a first in human clinical trial (NCT05669352)."

IO biomarker • Melanoma • Solid Tumor • IFNG • IRAK4 • MYD88

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (SNO 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Promising efficacy signal in secondary CNS lymphoma patients treated with emavusertib and ibrutinib (SNO 2025) - "Subsequently, the dose of emavusertib was decreased to 150 mg BID due to Grade 4 neutropenia, then increased to 200 mg AM and 150 mg PM once resolved. This patient achieved CRu within 60 days on treatment.The 2 patients presented here are supportive data for using the combination of emavusertib and ibrutinib in SCNSL."

Clinical • CNS Lymphoma • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypoglycemia • Infectious Disease • Lymphoma • Neutropenia • Secondary Central Nervous System Lymphoma • Septic Shock

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (SNO 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Preliminary safety and efficacy of emavusertib (CA-4948) in combination with ibrutinib in relapsed/refractory primary central nervous system lymphoma patients (SNO 2025) - P1/2 | "This regimen appears capable of overcoming resistance to prior BTKi therapy. Patient enrollment in this trial continues."

Clinical • Combination therapy • CNS Lymphoma • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma (ASH 2023) - P1/2 | "Key exclusion criteria: intraocular PCNSL without brain lesion or CSF involvement or significant co-morbidity. Key clinical assessments include brain imaging, CSF- and ocular examinations."

Clinical • IO biomarker • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • FLT3 • IRAK4 • MYD88

Promising efficacy signal in secondary CNS lymphoma patients treated with emavusertib and ibrutinib (WFNOS 2025) - "Subsequently, the dose of emavusertib was decreased to 150 mg BID due to Grade 4 neutropenia, then increased to 200 mg AM and 150 mg PM once resolved. This patient achieved CRu within 60 days on treatment.The 2 patients presented here are supportive data for using the combination of emavusertib and ibrutinib in SCNSL."

Clinical • CNS Lymphoma • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hypoglycemia • Infectious Disease • Lymphoma • Neutropenia • Secondary Central Nervous System Lymphoma • Septic Shock

Preliminary safety and efficacy of emavusertib (CA-4948) in combination with ibrutinib in relapsed/refractory primary central nervous system lymphoma patients (WFNOS 2025) - P1/2 | "This regimen appears capable of overcoming resistance to prior BTKi therapy. Patient enrollment in this trial continues."

Clinical • Combination therapy • CNS Lymphoma • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (WFNOS 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Analysis of genetic mutation profile and CNS pharmacokinetics in relapsed/refractory primary CNS lymphoma patients responding to novel emavusertib (IRAK4i) and BTKi combination (WFNOS 2025) - P1/2 | "Patients with MyD88 mutations showed expected promising preliminary efficacy to emavusertib + ibrutinib combination and may overcome BTKi resistance. Enrollment is ongoing."

Clinical • PK/PD data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • IRAK4 • MYD88

Targeting myddosome signaling to improve immunotherapy in melanoma brain metastases (WFNOS 2025) - P1/2 | "Targeted IRAK-4 inhibition with emavusertib reprograms suppressive TAMs and enhances response to anti-PD-1 therapy in MBM models. These findings support emavusertib as a promising adjuvant to ICB in MM, providing the foundation for a first in human clinical trial (NCT05669352)."

IO biomarker • Melanoma • Solid Tumor • IFNG • IRAK4 • MYD88

Targeting of Various Inflammatory Circuits Does Not Ameliorate Ineffective Hematopoiesis: Results of the Lucas and Canfire Studies Investigating IRAK4 or IL-1β Blockade to Target Anemia in Lower-Risk MDS (ASH 2024) - "Emavusertib treatment was associated with a reduction in neutrophil counts...Canakinumab treatment was well-tolerated with no reported SAEs...Despite the observed anti-inflammatory effects in the bone marrow, in LUCAS there was a paradoxical increase in inflammatory markers in peripheral blood, potentially due to compensatory mechanisms. These findings suggest that targeting multiple inflammatory pathways simultaneously may offer a more promising therapeutic strategy, such as the combination of IL-1β and IRAK4 inhibitors."

Anemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • ASXL1 • CSF1 • IL10 • IL15 • IL1B • IL1R1 • IL7 • IRAK4 • SETBP1 • U2AF1

Curis to Present at Upcoming 30th Annual SNO Meeting (PRNewswire) - "...Curis will report emavusertib and BTKi clinical data in Primary CNS Lymphoma (PCNSL) and Secondary CNS Lymphoma (SCNSL) in three presentations and preclinical data on emavusertib in an oral presentation..."

Clinical data • Preclinical • CNS Lymphoma