A phase 2 trial to study safety and efficacy of Capivasertib in patients with blood cancer where disease or cancer cell grows after a period of remission or response to treatment does not last very long

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Mar 2022 → 26 Oct 2024

Decision date (initial)

2024-07-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-516386-36-00

EudraCT number

2021-000870-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenomic, Efficacy, Pharmacogenetic, Prophylaxis, Diagnosis

To estimate the effectiveness of the module-defined study treatment by assessment of Objective Response Rate (ORR) based on Lugano 2014 Classification response criteria in each cohort as determined by Blinded Independent Central Review (BICR)

Secondary objectives 9

1. 1. To estimate the effectiveness of the module-defined study-treatment by assessment of Duration of Response (DoR)
2. 2. To estimate the effectiveness of the module-defined study treatment by assessment of Progression-Free Survival (PFS)
3. 3. To estimate the effectiveness of the module-defined study treatment by assessment of Overall Survival (OS)
4. 4. To assess patient-reported disease-related symptoms, functioning and health-related quality of life of the module-defined study treatment
5. 5. To assess patient-reported symptomatic AEs / tolerability of module-defined study treatment
6. 6. To estimate the effectiveness of the module-defined study treatment by assessment of Time to First Subsequent therapy or death (TFST) in each cohort
7. 7. To estimate the effectiveness of the module-defined study treatment by assessment of time to objective response (TTR) in each cohort
8. 8. To assess safety and tolerability of the module-defined study treatment
9. 9. To determine the PK of Capivasertib

Conditions and MedDRA coding

Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patient must be ≥ 18 years of age, at the time of signing the informed consent
2. ECOG performance status ≤ 2
3. Life expectancy > 6 months
4. Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing
5. Additional core inclusion criteria may apply, please refer to the protocol.
6. Additional Inclusion Criteria for Cohort 1A (R/R FL): Histologically confirmed diagnosis of FL Grade 1, 2, or 3a as assessed by investigator or local pathologist; Current need for systemic treatment based on the Investigator's opinion; Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy (including anti- CD20mAb and an alkylating agent). The treating physician should discuss with the patient all available treatment options, including the use of CAR-T cell therapy, evaluating benefits and risks before considering enrolment in this study; 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
7. Additional Inclusion Criteria for Cohort 1B (R/R MZL): Histologically confirmed MZL including splenic, nodal, and extranodal subtypes as assessed by investigator or local pathologist; Current need for systemic treatment based on the Investigator's opinion; 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); 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
8. Additional Inclusion Criteria for Cohort 1C (R/R MCL): 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; Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy; Patients must have received as prior therapies: a) BTK inhibitor and b) Anti-CD20 monoclonal antibody therapy. The treating physician should discuss with the patient all available treatment options, including the use of CAR-T cell therapy, evaluating benefits and risks before considering enrolment in this study; 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 8

1. 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 patient has been disease free for ≥ 2 years
2. With the exception of alopecia, any unresolved non-haematological toxicities from prior therapy ≥ CTCAE Grade 2 at the time of starting study treatment
3. Known medically apparent CNS lymphoma or leptomeningeal disease
4. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values at screening: a) Absolute neutrophil count < 1.0 × 10^9/L; < 0.75 × 10^9/L in participants with known bone marrow involvement of malignant disease b) Platelets < 75 × 10^9/L; < 50 × 10^9/L in participants with known bone marrow involvement of malignant disease c) Creatinine clearance < 50 mL/min per the Cockcroft and Gault formula
5. Clinically significant abnormalities of glucose metabolism as participants with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment OR Glycosylated haemoglobin ≥ 8.0% (63.9 mmol/mol)
6. Prior treatment with any of the following: a) 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 b) 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. c) Prior allogenic 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, CAR-T therapy) and/or autologous HSCT within 3 months from the first dose of capivasertib. d) Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s). e) Patients who, due to other medical conditions /prior history /concomitant medications are, in the investigator's opinion, at a risk of a 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.
7. Additional exclusion core criteria may apply, please refer to the protocol
8. Module 1 specific exclusion criteria: Follicular lymphoma grade 3B; Known transformation to aggressive lymphoma, eg, large cell lymphoma; Patients who, in the Investigator's opinion, require immediate cytoreductive therapy for disease control

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate is defined as the proportion of patients achieving either complete response or partial response according to the Lugano 2014 Classification for NHL as assessed by blinded independent central review (BICR)

Secondary endpoints 9

1. 1. 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
2. 2. 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
3. 3. Overall survival is defined as time from the date of first dose until the date of death due to any cause.
4. 4. Patient-reported disease-related symptoms, functioning and health related quality of life as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
5. 5. Patient-reported symptomatic AEs and overall side effect burden as measured by PGI-TT and selected items from PRO CTCAE.
6. 6. Time to first subsequent therapy or death (TFST) is defined as time from date of first dose until the start date of first subsequent anti-lymphoma therapy after discontinuation of study treatment or death due to any cause
7. 7. Time to objective response (TTR) is defined as time from date of first dose until the date of first documented objective response per the Lugano 2014 Classification for NHL as assessed by BICR
8. 8. Safety and tolerability will be evaluated in terms of AEs, vital signs, clinical laboratory and ECGs
9. 9. Plasma concentration of capivasertib pre-dose and post-dose

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Third parties 1

Locations

1 EU/EEA country · 2 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 8 files

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

Application history

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