Study of Capivasertib in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (CAPITAL)

A Modular Phase II, Open-Label, Multicentre Study to Assess the Efficacy and Safety of Capivasertib in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (CAPITAL)

This study is an open-label, multicenter Phase II study of capivasertib administered orally in participants with Relapsed or Refractory (R/R) B-cell Non-Hodgkin's Lymphoma (NHL).

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Capivasertib

Detailed Description

The study protocol follows a modular design. The study will investigate the safety and efficacy of capivasertib monotherapy in participants with R/R Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and Mantle Cell Lymphoma (MCL).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 6V5
      • Research Site
• Denmark
  • Aarhus N, Denmark, DK8200
    • Research Site
• France
  • Poitiers, France, 86021
    • Research Site
  • Villejuif Cedex, France, 94805
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Seoul, Korea, Republic of, 3722
    • Research Site
• Spain
  • Badalona, Spain, 08003
    • Research Site
  • Barcelona, Spain, 8035
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • Los Angeles, California, United States, 90095
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be ≥ 18 years of age, at the time of signing the informed consent
• Eastern Cooperative Oncology Group performance status ≤ 2
• Life expectancy > 6 months
• Female participants must not be breast-feeding and must have a negative pregnancy test (serum) prior to start of dosing

Module 1 specific inclusion criteria:

Additional Inclusion Criteria for Cohort 1A (R/R FL):

1. Histologically confirmed diagnosis of FL Grade 1, 2, or 3a as assessed by investigator or local pathologist
2. Current need for systemic treatment based on the Investigator's opinion
3. Relapsed, progressed or refractory (defined as failure to achieve at least a partial response [PR]) after at least 2 prior systemic lines of therapy (including anti-CD20 monoclonal antibody [mAb] and an alkylating agent)
4. Bi-dimensionally measurable disease on cross sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.

Additional Inclusion Criteria for Cohort 1B (R/R MZL):

1. Histologically confirmed MZL including splenic, nodal, and extranodal subtypes as assessed by investigator or local pathologist
2. Current need for systemic treatment based on the Investigator's opinion
3. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy (including at least one anti-CD20mAb directed regimen either as monotherapy or as chemoimmunotherapy; Helicobacter pylori eradication and radiation therapy alone will not be considered a systemic treatment regimen)
4. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis

Additional Inclusion Criteria for Cohort 1C (R/R MCL):

1. Histologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, as assessed by investigator or local pathologist
2. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy

3. Participants must have received as prior therapies

   Prior regimens must have included:

   • BTK inhibitor and
   • Anti-CD20mAb therapy
4. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis

Exclusion Criteria:

• Prior malignancy (other than the disease under study), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the participant has been disease free for ≥ 2 years
• With the exception of alopecia, any unresolved non-haematological toxicities from prior therapy ≥ Common Terminology Criteria for Adverse Events Grade 2 at the time of starting study treatment
• Known medically apparent central nervous system lymphoma or leptomeningeal disease

• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values at screening:

  1. Absolute neutrophil count < 1.0 × 10^9/L; < 0.75 × 10^9/L in participants with known bone marrow involvement of malignant disease
  2. Platelets < 75 × 10^9/L; < 50 × 10^9/L in participants with known bone marrow involvement of malignant disease
  3. Creatinine clearance < 50 mL/min per the Cockcroft and Gault formula
• Clinically significant abnormalities of glucose metabolism as participants with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment and Glycosylated haemoglobin ≥ 8.0% (63.9 mmol/mol)

• Prior treatment with any of the following:

  1. Any investigational agents or study drugs from a previous clinical study within 5 half lives or 2 weeks from the first dose of capivasertib in this study
  2. Strong inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort), or drugs that are sensitive to inhibition of CYP3A4 within 1 week prior to the first dose of study treatment
  3. Prior allogenic Haematopoietic stem cell transplant (HSCT) within 6 months from the first dose of capivasertib (patients > 6 months after allogenic HSCT are eligible in the absence of active graft-versus-host disease and concomitant immune suppressive therapy). Prior cellular therapies (eg, Chimeric antigen receptor T therapy) and/or autologous HSCT within 3 months from the first dose of capivasertib
  4. Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s)
  5. Participants who, due to other medical conditions /prior history /concomitant medications are, in the investigator's opinion, at a risk of a venous thromboembolism (VTE) and are not willing to accept the VTE prophylaxis, will be excluded. The initiation of an adequate VTE prophylaxis will be based on treating physician risk/benefit assessment and in agreement with the local management guidelines

Additional exclusion core criteria may apply, please refer to the protocol

Module 1 specific exclusion criteria:

1. Follicular lymphoma grade 3B
2. Known transformation to aggressive lymphoma, eg, large cell lymphoma
3. Participants who, in the Investigator's opinion, require immediate cytoreductive therapy for disease control

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capivasertib monotherapy; Participants with R/R FL, R/R MZL, and R/R MCL will receive capivasertib orally until progression of disease (PD) or unacceptable toxicity.	Drug: Capivasertib; Capivasertib will be taken orally twice a day (BD) 4 days on/ 3 days off.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate is defined as the proportion of patients achieving either complete response (CR) or partial response (PR) according to the Lugano 2014 Classification for non-Hodgkin lymphoma (NHL) as assessed by blinded independent central review (BICR).	First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	Duration of response is defined as the time from the date of first documented response until date of documented progression according to the Lugano 2014 Classification for NHL as assessed by BICR, or death due to any cause.	First documented response until date of documented progression or data-cut off date (21.6 Months)
Progression-free Survival	Progression-free survival is defined as the time from the date of first dose until documented disease progression according to the Lugano 2014 Classification for NHL as assessed by BICR, or death due to any cause. The analysis included all dosed patients, regardless of whether the patient withdrew from therapy, received another anti lymphoma therapy, or clinically progressed prior to progression according to the Lugano 2014 Classification for NHL.	First dose until documented disease progression or data cut-off date (21.6 Months)
Overall Survival (OS)	Overall survival is defined as time from the date of first dose until the date of death due to any cause. The analysis included all dosed patients, regardless of whether the patient withdrew from therapy or received another anti lymphoma therapy. Patients who had not died by the analysis DCO date were censored at their last known date of being alive before the DCO date. Patients who were known to be alive or dead after the DCO date were censored at the DCO date. Patients who were lost to follow-up were censored at the date when they were last known to have been alive.	First dose until data cut-off date (21.6 Months)
Number of Patients With Adverse Events and Serious Adverse Events	The safety and tolerability of the capivasertib treatment in each Cohort was assessed.	Screening (Day -28 to -1) until Post-treatment follow-up up to 30 days after last dose or long-term follow-up or study completion (Every 12 weeks until death or lost to follow-up, unless patient have withdrawn consent [up to 21.6 Months])
Plasma Concentration of Capivasertib Overtime	The plasma concentration of capivasertib when administered in patients in each Cohort was determined.	Cycle 1 (28-day treatment Cycle) Day 1 and on Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 1 Day 22 (Pre-dose and post-dose)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Publications and helpful links

Helpful Links

• Redacted Statistical Analysis Plan
• Redacted Clinical Study Protocol
• Redacted CSR synopsis

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): October 25, 2024

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 29, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Follicular Lymphoma; Marginal Zone Lymphoma; Mantle Cell Lymphoma; Capivasertib monotherapy
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: D361FC00001; 2021-000870-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No