A Phase 3, Randomized, Open-Label, Controlled, Multicenter Study of Zandelisib (ME-401) in Combination with Rituximab Versus Standard Immunochemotherapy in Patients with Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL) - The COASTAL Study

JRCT ID: jRCT2031230073

Registered date:15/05/2023

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Follicular Lymphoma, Marginal zone lymphoma
• Date of first enrollment: 16/08/2021
• Target sample size: 534
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Canada,Japan,Colombia,Japan,Czech Republic,Japan,France,Japan,Georgia,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Ireland,Japan,Italy,Japan,Korea,Japan,Netherlands,Japan,New Zeland,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,Serbia,Japan,Spain,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

<Study Design>
Subjects who meet the eligibility criteria will be randomly assigned in a 1:1 ratio to one of the treatment arms:
- Arm 1: R plus zandelisib
- Arm 2: R plus chemotherapy (CHOP or B)

<Study Treatments>
Zandelisib:
Administered in a 28-day cycle. Zandelisib capsule should be taken once a day on dosing days on the following schedule:
60 mg daily for the first two cycles of therapy (56 days) followed by:
60 mg for the first 7 days followed by 21 days off treatment in every subsequent 28-day cycle.

<Duration of Treatment>
- Arm 1:
R, 6 cycles (approximately 6 months)
Zandelisib, 26 cycles of therapy (approximately 24 months)
- Arm 2 (R-B and R-CHOP): 6 cycles (approximately 4 to 6 months)

Outcome(s)

• Primary Outcome: PFS as determined by the IRRC

Secondary Outcome

- Efficacy: ORR and CRR as determined by the IRRC
- OS
- TTNT
- PFS 2
- PRO : time to deterioration in the 9-item DRS-P subset of FlymSI-18
- PRO : time to improvement in the 9-item DRS-P subset of FlymSI-18
- PRO : functional and well-being (FWB) score and change from baseline in the DRS-P and FWB subscales and total score of FlymSI-18 at specified study visits
- PRO : change from baseline in EQ-5D-3L total score and VAS score at specified study visits
- Treatment-emergent AEs, serious AEs, and laboratory abnormalities

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Male or female subjects >= 18 years of age, >= 19 years in Korea, or 20 years for subjects in Japan and Taiwan, at time of signing informed consent.
2. Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to:
a) FL Gr 1, Gr 2, or Gr 3a.
b)MZL (splenic, nodal, or extra-nodal).
3. Subjects with relapsed or refractory disease who received >= 1 prior lines of therapy that must have included an anti-CD20 antibody in combination with cytotoxic chemotherapy or L, with or without subsequent maintenance therapy.
4. Subjects must have at least one bi-dimensionally measurable nodal lesion with the longest diameter >1.5 cm and/or an extranodal lesion >1.0 cm in the longest diameter (that has not been previously irradiated) according to the Lugano Classification.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
6. All AEs and laboratory toxicities related to prior therapy must resolve to Gr <= 1 prior to the start of the study therapy.
7. Subject is willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclude criteria

1. Histologically confirmed diagnosis of FL Gr 3b or transformed disease.
2. Subjects who received both R/O-B and R/O-CHOP (or other anthracycline-containing regimen) as previous lines of therapy, and those who received only single agent anti-CD20 mAb therapy as prior line of treatment.
3. Prior therapy with PI3K inhibitors.
4. Any uncontrolled clinically significant illness including, but not limited to, active infections requiring systemic antimicrobial therapy, hypertension, angina, arrhythmias or other uncontrolled cardiovascular condition, pulmonary disease, autoimmune dysfunction, and urinary infection or flow obstruction.
5. Hypersensitivity or other clinically significant reaction to the study drug or its inactive ingredients or other therapy used in the study.
6. Previous or concurrent cancer that is distinct in primary site or histology from indolent B cell NHL within 3 years before start of study treatment.
7. Any illness or medical conditions that are unstable or could jeopardize the safety of the subjects and their compliance in the study. Inability to understand and sign informed consent form.

Related Information

• Primary Sponsor: Hanaya Miyoko
• Secondary Sponsor: Kyowa Kirin Co., Ltd.
• Secondary ID(s): NCT04745832