CA-4948-203: A Ph2 Study of Emavusertib + an Approved BTKi in Patients with CLL and Other B-cell Malignancies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Curis Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 May 2026 → ongoing

Decision date (initial)

2026-03-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Curis, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacodynamic, Pharmacogenetic, Safety, Pharmacokinetic

Cohort 1 and Cohort 2:
• Assess the anticancer activity of emavusertib in combination with zanubrutinib

Secondary objectives 1

1. Cohort 1 and Cohort 2: • Further assess anticancer activity of emavusertib in combination with zanubrutinib • Evaluate the safety and tolerability of emavusertib in combination with zanubrutinib • Assess the exposure profile of emavusertib in combination with zanubrutinib

Conditions and MedDRA coding

Chronic Lymphocytic Leukemia and Other B-cell Malignancies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Age ≥18 years of age with life expectancy of ≥ 3 months.
2. 2. Eastern Cooperative Oncology Group Performance Status of ≤2;
3. 3. Histopathologically confirmed diagnosis of CLL per the World Health Organization 2016 classification;
4. 4. At least 1 criterion for measurable disease per iwCLL; creatine phosphokinase (CPK) < 2.5 × upper limit of normal (ULN);
5. 5. Ability to tolerate contrast-enhanced computed tomography (CT) scan;
6. 6. Ability to swallow/retain oral medications;
7. 7. Negative serum pregnancy test in women of childbearing potential (WOCP);
8. 8. WOCP and men who partner with WOCP must use highly effective contraceptive methods during study and 180 days after the last dose of study treatment;
9. 9. Ability to understand/sign a written informed consent document.
10. 10. For Cohort 1 only: Patient must be in a PR or PR-L and MRD+, must have detectable MRD as determined by the ClonoSEQ assay, actively taking zanubrutinib for at least 12 months, acceptable organ function (protocol-defined) at Screening within 28 days prior to Cycle 1 Day 1 (C1D1)
11. 11. For Cohort 2 only: Relapsed disease (protocol-defined) for which patients are ineligible for or exhausted standard of care options; Actively taking zanubrutinib and with direct progression on zanubrutinib and no other anticancer therapy administered since; Acceptable organ function (protocol-defined) at Screening within 28 days prior to C1D1.

Exclusion criteria 12

1. 1. Active second malignancy unless in remission with life expectancy > 2 years;
2. 2. Active malignancy other than CLL requiring systemic therapy;
3. 3. high-risk CLL TP53 mutations and 17P deletion;
4. 4. History of Grade ≥ 3 rhabdomyolysis without complete recovery;
5. 5. Prior chimeric antigen receptor-T cell therapy;
6. 6. Prior investigational drugs within 28 days or 5 half-lives, whichever is shorter, prior to C1D1: allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to C1D1, or clinically significant graft-versus-host disease (GVHD) requiring ongoing uptitration of immunosuppressive medications prior to Screening: Prior systemic anticancer treatment received within 21 days or 5 half-lives, whichever is shorter, prior to C1D1 (with the exception of zanubrutinib, which may be continued until the day before C1D1);
7. 7. Receiving the following medications within 7 days or 5 half-lives, whichever is shorter, prior to C1D1: Medications that have a high risk of causing prolonged QT interval, corrected (QTc) and/or Torsades de Pointes, Peg-filgrastim or equivalent, St John’s Wort;
8. 8. History of or ongoing drug-induced pneumonitis, History of stroke or intracranial hemorrhage within 6 months prior to C1D1, Requirement for anticoagulation with warfarin or equivalent vitamin K antagonists, including dual antiplatelet agents, within 5 half-lives of the anticoagulant or 7 days, whichever is longer, prior to C1D1;
9. 9. Vaccinated with a live-attenuated vaccine within 4 weeks prior to C1D1: History of hypersensitivity or anaphylaxis to ema, approved BTKi, or any of their excipients;
10. 10. History of Stevens-Johnson syndrome or toxic epidermal necrolysis;
11. 11. Intolerance to contrast-enhanced CT scan: Major surgery < 28 days prior to C1D1, minor surgery < 7 days prior to C1D1. Viral infections (protocol-defined);
12. 12. Concomitant illness that would preclude safe participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Cohort 1: undetectable measurable residual disease (uMRD) rate: percentage of patients achieving uMRD as measured in peripheral blood mononuclear cells (PBMCs) by the ClonoSEQ assay. Bone marrow aspirate is required to confirm a CR and uMRD by peripheral blood.
2. 2. Cohort 2: ORR: percentage of patients achieving a complete response (CR), or PR using iwCLL Response Criteria guidelines (Hallek et al, 2018)

Secondary endpoints 3

1. 1. Cohort 1: Duration of uMRD, Time to measurable residual disease (MRD) conversion, complete response (CR) rate, Duration of CR, Time to CR
2. 2. Cohort 2: Duration of response (DOR), Time to response
3. 3. Cohort 1 and Cohort 2: • Progression-free survival (PFS), Overall survival (OS) • Incidence of treatment-emergent adverse events (TEAEs) and treatment-related AEs, physical examinations, vital signs, electrocardiograms (ECGs), and laboratory values • PK parameters: Cmax, Tmax, AUC0-t, and Cmin for emavusertib and zanubrutinib

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Curis Inc.

Sponsor organisation

Curis Inc.

Address

128 Spring Street Suite 500 Building C

City

Lexington

Postcode

02421-7800

Country

United States

Scientific contact point

Organisation

Curis Inc.

Contact name

Chief Medical Officer Ahmed Hamdy, MD

Public contact point

Organisation

Curis Inc.

Contact name

Medical Affairs

Third parties 11

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications