A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered CA-4948 in Patients with Relapsed or Refractory Hematologic Malignancies

Overview

About this study

This is a multi-center, open-label trial of orally administered CA-4948 monotherapy in adult patients with Relapsed or Refractory NHL. The trial will be conducted in 2 parts: an initial Dose Escalation Phase (Part A) of CA-4948 in patients with Relapsed or Refractory Non-Hodgkin Lymphoma, (RR NHL) and a Dose Expansion Phase (Part B) of CA-4948 in patients with RR NHL with and without myeloid differentiation primary response 88 (MYD88) mutations. During Part B, patients will be enrolled regardless of MYD88 mutation status.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

1. Males and females greater than or equal to 18 years of age

2. Life expectancy of at least 3 months

3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

4. For Part A1: Diagnosis of histopathologically confirmed B-cell hematological
malignancy (as per the World Health Organization [WHO] 2016 classification; Swedow
2016); eligible subtypes include follicular lymphoma, MZL, DLBCL, mantle cell
lymphoma, and WM/LPL without the urgent need for treatment hyperviscosity.

For Part A2: Diagnosis of histopathologically confirmed B-cell NHL, as per the WHO 2016
classification (Swerdlow et al. 2016). Eligible NHL subtypes include follicular lymphoma,
MZL, mantle cell lymphoma, DLBCL(including extranodal lymphomas of leg-, testicular-, or
NOS type), CLL/SLL, primary or secondary CNS lymphoma and WM/LPL.

For Part B: Diagnosis of histopathologically confirmed B-cell NHLs, including applicable
confirmation as per the WHO 2016 classification (Swerdlow et al. 2016):

- Cohort 1: Marginal zone lymphoma

- Cohort 2: ABC-DLBCL, or extranodal subtypes: Leg-, testicular-, or NOS-type. The
population will be enriched for MYD88 L265P mutations. As this occurs more frequently
in the ABC-DLBCL(activated B-cell (Hans et al. 2004) subtype, all patients with this
subtype qualify for enrollment. If the MYD88 mutation status is unknown at baseline,
the lymphoma will be tested for MYD88 mutations.

- Cohort 3: Primary CNS Lymphoma (PCNSL) only. If the MYD88 mutation status is unknown
at baseline, the lymphoma will be tested for MYD88 mutations.

- Cohort 4: Patients receiving ibrutinib monotherapy who have developed adaptive,
secondary resistance. Indications include:

- MCL, MZL, CLL/SLL, or WM/LPL

- Indications for which ibrutinib is NCCN-listed (e.g., PCNSL)

- Patients with NHL and known myddosome mutations

- Patients may be candidates for maintaining ibrutinib while emavusertib will be
added for resistance reversal. A brief gap of ibrutinib therapy of <3 weeks is
acceptable.

Exclusion Criteria:

1. Patient with active central nervous system (CNS) involvement other than PCNSL at study
entry are ineligible.

2. Radiotherapy delivered to non-target lesions involving >25% of bone marrow within one
week prior to starting study treatment or delivered to target lesions that will be
followed on the study (NOTE: prior sites of radiation will be recorded)

3. Any prior anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy,
etc., received within 14 days prior to start of study treatment (with the exception of
ibrutinib for Parts A2 and B, which may be continued as part of this study without
interruption)

4. Current or planned glucocorticoid therapy, with the following exceptions:

1. Doses ≤ 10 mg/day prednisolone or equivalent is allowed, provided that the
steroid dose has been stable or tapering for at least 14 days prior to the first
dose of study treatment

2. Inhaled, intranasal, intraarticular and topical steroids are permitted

5. Use of any investigational agent within 21 days or 5 half-lives, whichever is shorter,
prior to start of study treatment

6. Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy,
with the exception of alopecia, that has not resolved to Grade ≤ 1 within 7 days prior
to start of study treatment unless approved by the Medical Monitor

7. Known allergy or hypersensitivity to any component of the formulation of emavusertib
(or ibrutinib for entry into Parts A2 or B) used in this study

8. B-cell NHL of the following subtypes:

1. Burkitt lymphoma

2. Lymphoblastic lymphoma or leukemia

3. Post-transplantation lymphoproliferative disorder

4. Known primary mediastinal, ocular, or epidural, DLBCL

5. WM patients requiring urgent treatment due to hyperviscosity

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 10/12/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Grzegorz Nowakowski, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Han Tun, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Allison Rosenthal, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
.
CLS-20403518

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