A Phase 2, Open-Label, Multicenter, Basket Study Evaluating the Safety and Efficacy of Brexucabtagene Autoleucel in Adults with Rare B-cell Malignancies (ZUMA-25) – Substudy D – Relapsed/Refractory Hairy Cell Leukemia (HCL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kite Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Apr 2023 → 26 Jun 2024

Decision date (initial)

2023-02-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Kite Pharma Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Therapy, Pharmacokinetic

The primary objective of ZUMA-25 is to evaluate the efficacy of brexucabtagene autoleucel in subjects with rare B-cell malignancies, by determining the Response Rates as defined within the substudies by central assessment. The primary objective of ZUMA-25 substudy D (HCL) is to evaluate the efficacy of brexucabtagene autoleucel in subjects with HCL by determining the objective response rate (ORR) by central assessment.

Secondary objectives 7

1. The secondary objectives of ZUMA-25 as per the master protocol are: •To evaluate the Complete Response (CR) by central assessment as defined within each substudy.
2. •Determine response durability
3. •Determine survival status
4. •Determine survival status without progression
5. •Determine the time to next treatment (TTNT) after administration of brexucabtagene autoleucel
6. •Determine the time to first response
7. The Substudy D (HCL) specific secondary objective is to evaluate the efficacy of brexucabtagene autoleucel in subjects with HCL by ORR by investigator assessment

Conditions and MedDRA coding

Relapsed/Refractory Hairy Cell Leukemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. •Male or female 18 years of age or older at the time of signing the informed consent
2. •Presence of toxicities due to prior therapy must be stable and recovered to Grade 1 or lower
3. •ECOG performance status score of 0 or 1.
4. •Adequate hematologic and end-organ function.
5. •Participants of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception
6. • Individuals must have histologically confirmed hairy cell leukemia (HCL) with a need for therapy based on at least one of the following criteria: - neutrophils < 1.0 x 10^9/L - platelets < 100 x 10^9/L - hemoglobin < 11 g/dL - symptomatic splenomegaly - symptomatic lymphadenopathy
7. • Individuals must have received: - At least 2 prior therapies, including at least a purine nucleoside analog (PNA) and moxetumomab pasudotox if eligible and available.

Exclusion criteria 5

1. •Prior CAR therapy or treatment with any anti-CD19 therapy
2. •HIV-positive patients, unless taking appropriate anti-HIV medications, having an undetectable viral load by quantitative polymerase chain reaction (qPCR) and a CD4 count > 200 cells/uL.
3. •History or presence of detectable cerebrospinal fluid malignant cells or brain metastases, with the exception of prior CNS disease in WM
4. •History of autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
5. • Prior history of allogeneic stem cell transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of ZUMA-25 as per the master protocol is response rates by central assessment as defined in each substudy. The primary end point of Substudy D (HCL) is ORR by central assessment defined as the proportion of subjects who achieve either complete response (CR) or partial response (PR)

Secondary endpoints 7

1. The secondary endpoints of ZUMA-25 as per the master protocol are: • CR rate by central assessment as defined in each substudy
2. • Duration of Response
3. • Overall Survival
4. • Progression-free survival
5. • Time to next treatment defined as the time from enrollment (for Full Analysis Set [FAS]) or brexucabtagene autoleucel infusion (for modified intention to treat [mITT]) to the initiation of subsequent anticancer therapy/treatment
6. • Time to first response from brexucabtagene autoleucel infusion to the first response as defined in the substudy
7. The Substudy D (HCL) specific secondary endpoint is ORR by investigator assessment defined as the proportion of subjects who achieve either CR or PR

Investigational products

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

Test 1

Auxiliary 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kite Pharma Inc.

Sponsor organisation

Kite Pharma Inc.

Address

2225 Colorado Avenue

City

Santa Monica

Postcode

90404-3505

Country

United States

Scientific contact point

Organisation

Kite Pharma Inc.

Contact name

EU Clinical Trials Support

Public contact point

Organisation

Kite Pharma Inc.

Contact name

EU Clinical Trials Support

Third parties 10

Locations

7 EU/EEA countries · 18 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

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

Application history

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