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

Phase I trial of emavusertib (CA-4948) in combination with cisplatin, gemcitabine, and durvalumab in patients with untreated advanced or metastatic biliary tract cancer. (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

A Trial Comparing Three Different Treatment Options for Adults With Low-Risk Myelodysplasia and Anemia (A MyeloMATCH Treatment Trial) (clinicaltrials.gov) - P2 | N=270 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Sep 2026 ➔ Dec 2026

Trial initiation date • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Canakinumab or emavusertib for anemia in lower-risk MDS: results of the CANFIRE and LUCAS phase 2, open-label, multicenter trials. (PubMed, Commun Med (Lond)) - P2 | "Inhibition of IL-1β or IRAK4 signaling with canakinumab or emavusertib did not result in hematologic improvement in patients with LR-MDS."

Journal • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • IL1B • IRAK4

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

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

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

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

A Trial Comparing Three Different Treatment Options for Adults With Low-Risk Myelodysplasia and Anemia (A MyeloMATCH Treatment Trial) (clinicaltrials.gov) - P2 | N=270 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jun 2026 ➔ Sep 2026

Trial initiation date • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Curis is announcing that it has achieved the previously stated goal of dosing the first five patients in the TakeAim CLL study and reaffirmed its expectation to report initial CLL data in 5-10 patients in December 2026. (Curis Press Release)

Trial status • Chronic Lymphocytic Leukemia

Curis, Inc…announced that it will host a webcast on Wednesday, July 22 at 8:30 a.m. ET to discuss positive updated clinical data in the TakeAim Lymphoma study, its ongoing registrational study in Primary CNS Lymphoma (PCNSL) (Curis Press Release) - "Take Aim Lymphoma: The PCNSL update includes data for 7 BTK-naive patients and 39 BTKi-experienced patients...BTKi-naive evaluable patients (100% ORR); BTKi-naive all patients (86% ORR); BTKi-naive previous data patients (71% ORR). BTKi-experienced evaluable patients (33% ORR); BTKi-experienced all patients (26% ORR); BTKi-experienced previous data patients (27% ORR)."

P1/2 data • CNS Lymphoma • Primary Central Nervous System Lymphoma

Curis, Inc…announced that it will host a webcast on Wednesday, July 22 at 8:30 a.m. ET to…provide updated guidance on year-end data in the TakeAim CLL study, its ongoing Phase 2 study in Chronic Lymphocytic Leukemia (Curis Press Release) - "TakeAim CLL: Today, the Company announced that the number of patients consented has increased to 10, with the first five expected to be dosed by the end of July. The company is also increasing its guidance for year-end CLL data from 5 patients to 5-10 patients in December 2026."

P2 data • Trial status • Chronic Lymphocytic Leukemia

Curis Announces Eleven Active Clinical Sites in TakeAim CLL Study, Reaffirms Patient Dosing Guidance, and Reports Stockholder Approval of Reverse Stock Split (PRNewswire) - "The Company also reaffirmed its guidance for the dosing of the initial five patients in the TakeAim CLL study by the end of July 2026, with data expected in December 2026."

Enrollment open • P2 data • Chronic Lymphocytic Leukemia

Improving Immune Checkpoint Blockade Efficacy in Melanoma Brain Metastases through Myddosomal inhibition with Emavusertib. (PubMed, Mol Cancer Ther) - "Emavusertib in combination with anti-PD-1 therapy results in improved tumor-infiltrating lymphocyte recruitment, decreased myeloid derived suppressor cell function, and upregulation of interferon γ signaling resulting in improved survival in aggressive mouse models of melanoma brain metastases. This work supports the development of combination strategies of emavusertib with immune checkpoint blockade in melanoma brain metastases."

Checkpoint inhibition • Journal • CNS Lymphoma • Hematological Malignancies • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Solid Tumor • IFNG • IRAK4 • MYD88

A phase I trial of emavusertib (CA-4948) in combination with gemcitabine and nab-paclitaxel in metastatic or unresectable pancreatic ductal adenocarcinoma (PDAC). (ASCO 2026) - P1 | "At this early stage of the study, emavusertib in combination with G/nP as second-line therapy for metastatic or unresectable PDAC has a manageable toxicity profile and shows encouraging preliminary results with an ORR of 20% and DCR of 60%, compared to historical ORR of 13-17% and DCR of 46-58% for G/nP, respectively. Escalation to DL4 is ongoing, which will be followed by dose expansion at RP2D."

Combination therapy • Metastases • P1 data • Fibrosis • Hematological Disorders • Neutropenia • Oncology • Pancreatic Ductal Adenocarcinoma • IRAK4

A heterobifunctional IRAK4-targeting degrader impairs myddosome signaling in acute kidney injury and ameliorates kidney fibrosis. (PubMed, Commun Biol) - "In vivo, KTX-545 showed increased efficacy compared to the small molecule IRAK4 kinase inhibitor CA-4948 in ameliorating fibrosis following ischemia/reperfusion injury. Collectively, our results indicate that targeted degradation of IRAK4 is a new promising therapeutic approach for the treatment of renal fibrosing disorders."

Journal • Acute Kidney Injury • Cardiovascular • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • Targeted Protein Degradation • IRAK4

CA-4948 Added to Standard Chemotherapy to Treat Metastatic or Unresectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=43 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Curis Provides First Quarter 2026 Business Update (Curis Press Release) - "Upcoming Milestones: (i) Curis expects to announce the dosing of the initial 5 patients in the TakeAim CLL combination study with zanubrutinib by mid-2026, with data expected in December 2026; (ii) Also, the Company expects updated emavusertib clinical data from the TakeAim Lymphoma combination study with ibrutinib in patients with R/R PCNSL in the first half of 2027."

P1/2 data • Chronic Lymphocytic Leukemia • CNS Lymphoma

CA-4948 Added to Standard Chemotherapy to Treat Metastatic or Unresectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=43 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jun 2028 ➔ Apr 2029 | Trial primary completion date: Sep 2027 ➔ Jul 2028

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • HER-2

Emavusertib (CA-4948) in Combination With Cisplatin, Gemcitabine, and Durvalumab in Patients With Untreated Advanced or Metastatic Biliary Tract Cancer (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor

Trial in progress: A phase 1b single-arm, open-label, study of emavusertib (CA-4948) in combination with azacitidine and venetoclax in acute myeloid leukemia patients in complete response with measurable residual disease (AACR 2024) - "In this Phase 1b trial, MRD can be evaluated by local testing of bone marrow. Key exclusion criteria include residual toxicities and significant comorbidities."

Clinical • Combination therapy • P1 data • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • IRAK4

HPB-092: A novel FLT3 and IRAK4 dual inhibitor for the treatments of AML and MDS (AACR 2025) - "Compared to the approved FLT3 inhibitors gilteritinib and quizartinib, and the clinical-stage FLT3/IRAK4 dual inhibitor CA-4948, HPB-092 showed comparable or superior inhibitory potency against mutated forms of FLT3, improved IRAK4 inhibition, better selectivity, minimal inhibition of CYP3A4, no hERG activity, and an overall favorable safety profile, potentially benefiting a broader range of hematological malignancies. HPB-092 has received FDA clearance for a phase 1 dose-escalation and expansion study to assess its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in adult patients with relapsed or refractory AML, particularly those with FLT3 mutations and U2AF1 or SF3B1 mutations, at a leading cancer center in the US."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CYP3A4 • FLT3 • IRAK4 • SF3B1 • U2AF1

CA-4948 (emavusertib) improves treatment response of preclinical metastatic brain melanoma to anti-PD-1 immune checkpoint blockade (AACR 2024) - "Conclusion Targeted inhibition of IRAK-4 with CA-4948 improves immune surveillance and activation in preclinical models when combined with anti-PD-1 ICB, resulting in reduced tumor growth and increased survival. Thus, CA-4948 may be an effective adjuvant treatment strategy alongside anti-PD-1 ICB for the treatment of metastatic melanoma."

Checkpoint block • Checkpoint inhibition • IO biomarker • Metastases • Preclinical • Brain Cancer • CNS Tumor • Melanoma • Oncology • Solid Tumor • CX3CR1 • IFNG • IRAK4

CA-4948 102: Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1/2 | N=366 | Suspended | Sponsor: Curis, Inc. | Recruiting ➔ Suspended

IO biomarker • Monotherapy • Trial suspension • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • SF3B1 • U2AF1

CA-4948-203: A Ph2 Study of Emavusertib + an Approved BTKi in Patients with CLL and Other B-cell Malignancies (clinicaltrialsregister.eu) - P1/2 | N=40 | Not yet recruiting | Sponsor: Curis Inc.

New P1/2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology