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 A – Relapsed/Refractory Waldenstrom Macroglobulinemia (WM)

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 → 21 Jun 2023

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, Pharmacodynamic, Therapy, Pharmacokinetic, Efficacy

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 A is to evaluate the efficacy of brexucabtagene autoleucel in WM by determining the combined rate of complete response (CR) and very good partial response (VGPR) by central assessment per the Sixth International Workshop in WM {Owen 2013}

Secondary objectives 9

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. Substudy A (WM) specific secondary objectives are: • To determine the efficacy of brexucabtagene autoleucel in subjects with WM, by determining the Objective Response Rate (ORR) by central assessment
8. • To determine the combined rate of CR and VGPR by investigator assessment
9. • To determine the rates of individual responses by central assessment

Conditions and MedDRA coding

Relapsed/Refractory Waldenstrom Macroglobulinemia (WM)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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. •Confirmed clinicopathological diagnosis of WM in accordance with the consensus panel of the Second International Workshop on WM (see Section 12.3.2)
7. •Relapsed or refractory disease after 2 or more lines of therapy
8. oPrior therapy must have included a BTK inhibitor. Also, chemotherapy and/or a proteasome inhibitor must have been attempted, with either subsequent documented disease progression or no response (stable disease)
9. • Requiring treatment as defined in the recommendations from the Second International Workshop on WM
10. • Measurable disease, defined as presence of serum immunoglobulin (Ig) M with a minimum IgM level of > 2 times the upper limit of normal of each institution is required.
11. • The inclusion criteria concerning washout periods prior to leukapheresis in the KT US 568-0138 master protocol must be met, with the exception that ibrutinib may be continued through leukapheresis and up to 5 half-lives (30 hours) prior to the start of lymphodepletion

Exclusion criteria 8

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. • History of allogeneic stem cell transplantation. A prior autologous stem cell transplantation is allowed, but at least 6 months should have elapsed
6. • Plasmapheresis for symptomatic hyperviscosity or serum IgM > 5,000 mg/dL < 35 days prior to the screening IgM assessment
7. • Exclusion of IgM monoclonal gammopathy of undetermined significance or IgM multiple myeloma
8. • Presence of a central nervous system involvement (Bing-Neel syndrome). Subjects with a prior history of Bing-Neel syndrome are eligible if they show a negative cerebrospinal fluid and no involvement by imaging

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 A (WM) is combined rate of CR and VGPR rate by central assessment defined as the proportion of subjects who achieve either CR or VGPR .

Secondary endpoints 9

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. Substudy A (WM) specific secondary endpoints are: •ORR, defined as the proportion of subjects who achieve a best response of CR, VGPR, or partial response (PR)
8. • Combined CR and VGPR rate by investigator assessment defined as the proportion of subjects who achieve either CR or VGPR
9. • Rate of VGPR and PR, separately

Investigational products

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

Test 1

Auxiliary 9

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

Application history

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