Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as CA-4948
Emavusertib · 4 trials · 13 indications
Graded using CTCAE version 5.0.
The number of participants with a dose-limiting toxicity (DLT) in the first treatment cycle
MTD determined by the highest dose level studied at which fewer than 2 out of 6 subjects (\<33%) experience a dose limiting toxicity.
RP2D selected based on overall tolerability data from all participants treated at different dose levels and will not exceed the MTD.
| Arm | Type | Description |
|---|---|---|
| Cohort 1: Emavusertib and Zanubrutinib | EXPERIMENTAL | Participants in Cohort 1 include CLL participants who have been on zanubrutinib for at least 12 months and are currently in a partial response (PR) or partial response with lymphocytosis (PR-L) and measurable residual disease positive (MRD+). In Part A, participants will receive one of two doses of emavusertib twice daily (BID) and an approved dose of zanubrutinib per label. In Part B, additional participants will be enrolled in an expansion if pre-defined criteria for Part A are met. Participants will receive one of two doses of emavusertib BID and an approved dose of zanubrutinib per label. |
| Cohort 2: Emavusertib and Zanubrutinib | EXPERIMENTAL | Participants in Cohort 2 include relapsed CLL participants who have directly progressed on zanubrutinib after a confirmed response (PR or better lasting 6 months or longer). In Part A, participants will receive one of two doses of emavusertib BID and an approved dose of zanubrutinib per label. In Part B, additional participants will be enrolled in an expansion if pre-defined criteria for Part A are met. Participants will receive one of two doses of emavusertib BID and an approved dose of zanubrutinib per label. |
| Dose Escalation Dose Level 0 (starting dose): Emavusertib + Gemcitabine + Cisplatin + Durvalumab | EXPERIMENTAL | * Treatment will be administered on a 21-day cycle. * Emavusertib will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with emavusertib on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with emavusertib as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9). |
| Dose Escalation Dose Level -1: Emavusertib + Gemcitabine + Cisplatin + Durvalumab | EXPERIMENTAL | * Treatment will be administered on a 21-day cycle. * Emavusertib will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with emavusertib on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with emavusertib as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9). |
| Dose Expansion: Emavusertib + Gemcitabine + Cisplatin + Durvalumab | EXPERIMENTAL | * Treatment will be administered on a 21-day cycle. * Emavusertib will be self-administered at the assigned dose by mouth twice per day at approximately 12-hour intervals. * Cisplatin and gemcitabine will be administered intravenously on Days 1 and 8 for up to 8 total cycles as per standard of care. Up to 2 cycles of gemcitabine and cisplatin, with or without durvalumab, may be given off protocol prior to enrollment; therefore some patients may receive only 6 or 7 cycles of gemcitabine, cisplatin, and durvalumab in combination with emavusertib on study. Durvalumab will be administered IV on Day 1 of each cycle. Durvalumab will continue in combination with emavusertib as maintenance therapy starting with Cycle 9 (or earlier, if patient discontinues cisplatin and gemcitabine prior to Cycle 9). |
| Dose Escalation (CA4948 + FOLFOX + Nivolumab) | EXPERIMENTAL | * CA4948 (dose will depend on dose level assigned) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days. * Each cycle is 14 days. |
| Dose Expansion Cohort A (CA4948 + FOLFOX + Nivolumab) | EXPERIMENTAL | * CA4948 (dose will be the recommended phase II dose found in the dose escalation portion of study) twice daily by mouth. Standard of care mFOLFOX7 every 14 days. Nivolumab every 14 days. * Each cycle is 14 days. |
| Dose Expansion Cohort B (CA4948 + FOLFOX + Pembrolizumab + Trastuzumab) | EXPERIMENTAL | * CA4948 (dose will be the recommended dose found in the dose escalation portion of study) twice daily by mouth Standard of care mFOLFOX7 every 14 days. Pembrolizumab on day 1 of every 3 cycles. Trastuzumab every 14 days. * Each cycle is 14 days. |
| Emavusertib (CA-4948) dose escalation | EXPERIMENTAL | Part A1: Dose-level cohorts with up to approximately 6 participants each will be used to define the Maximum Tolerated Dose (MTD) for emavusertib. |
| Emavusertib (CA-4948) and ibrutinib dose escalation | EXPERIMENTAL | Part A2: Evaluate escalating dose levels of oral emavusertib in combination with 560 mg QD or 420 mg QD of oral ibrutinib. The starting dose of emavusertib to be used in combination will be 200 mg BID. It is anticipated that 12 to 20 participants at a potential dose level will be required to establish optimal combination dosing. |
| Emavusertib (CA-4948) and ibrutinib dose expansion | EXPERIMENTAL | In two Expansion Cohorts (Part B), emavusertib in combination with ibrutinib will be administered in participants with R/R PCNSL who have progressed on a BTKi. In Cohort 1, emavusertib 100 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles. In Cohort 2, emavusertib 200 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles. |
| Emavusertib (CA-4948) and ibrutinib | EXPERIMENTAL | In this part of the study (Part C), eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will receive 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD. Treatments will be administered continuously in 28-day treatment cycles. |
| Name | Type | Description |
|---|---|---|
| Emavusertib | DRUG | Oral tablets |
| Zanubrutinib | DRUG | Oral capsules |
| Gemcitabine | DRUG | Standard of care. |
| Cisplatin | DRUG | Standard of care. |
| Durvalumab | BIOLOGICAL | Standard of care. |
| CA-4948 | DRUG | Provided by Curis, Inc. |
| Nivolumab | BIOLOGICAL | 240 mg IV on Day 1 of each cycle |
| Pembrolizumab | BIOLOGICAL | 400 mg IV on Day 1 of every 3 cycles (C1D1, C4D1, C7D1,…) and dosing may continue for a max of 2 years |
| Trastuzumab | DRUG | 6 mg/kg IV loading dose on Cycle 1 Day 1 and 4 mg/kg IV on Day 1 of every subsequent cycle |
| mFOLFOX7 | DRUG | Standard of care |
| Ibrutinib | DRUG | Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD. |
Inclusion Criteria (All Parts): 1. Males and females ≥ 18 years of age. 2. Life expectancy of ≥ 3 months. 3. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2. 4. Histopathologically confirmed diagnosis of CLL (medical record is acceptable), as per the World Health Organization 20...
Emavusertib is an investigational small molecule oncology drug developed by Curis, Inc. (ticker CRIS). It is being studied in chronic lymphocytic leukemia, gastric cancer, metastatic biliary tract cancer, and relapsed hematologic malignancies. It is also known as CA-4948. Emavusertib remains in clinical development and is not approved for commercial use.
Emavusertib targets IRAK4, a kinase involved in inflammatory and immune signaling pathways. By inhibiting IRAK4, the drug is designed to interfere with signaling that supports tumor cell survival and growth, particularly in B-cell malignancies and other cancers where this pathway is active. It is a small molecule administered as an oral therapy.
Emavusertib is developed by Curis, Inc., a biopharmaceutical company that trades under the ticker symbol CRIS. Curis is running the clinical development program for emavusertib across several cancer indications, including chronic lymphocytic leukemia, biliary tract cancer, gastric cancer, and relapsed hematologic malignancies.
Emavusertib is in Phase 2 clinical development. The most advanced study is a Phase 2 trial in chronic lymphocytic leukemia and other B-cell malignancies. Additional Phase 1 trials are evaluating the drug in metastatic biliary tract cancer, gastric and esophageal cancer, and relapsed or refractory primary central nervous system lymphoma. It is investigational and not approved.
Emavusertib is being evaluated in four recruiting trials. NCT07271667 is a Phase 2 study in chronic lymphocytic leukemia and B-cell malignancies. NCT07107750 is a Phase 1 trial in metastatic biliary tract cancer. NCT05187182 is a Phase 1 study in gastric and esophageal cancer. NCT03328078 is a Phase 1 trial in relapsed or refractory primary central nervous system lymphoma.
Yes, emavusertib is the same drug as CA-4948. CA-4948 is the earlier code name used for the compound, and it still appears in the titles of several clinical trials, including NCT05187182 and NCT03328078. Both names refer to the same investigational IRAK4 inhibitor being developed by Curis, Inc.