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

Study identifier:D361FC00001

ClinicalTrials.gov identifier:NCT05008055

EudraCT identifier:2021-000870-27

CTIS identifier:2024-516386-36-00

Study Complete

Official Title

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)

Medical condition

Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Phase

Phase 2

Healthy volunteers

Study drug

Capivasertib

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 03 Nov 2021

Primary Completion Date: 22 Aug 2023

Study Completion Date: 25 Oct 2024

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2024 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

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:
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
- 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:
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 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
d) Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s)
e) 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

Location

Research Site

Seoul, Republic of Korea, 3722

Location

Research Site

Seoul, Republic of Korea, 06351

Location

Research Site

Busan, Republic of Korea, 49241

Location

Research Site

Los Angeles, CA, United States, 90095

Location

Research Site

Houston, TX, United States, 77030

Location

Research Site

Madrid, Spain, 28046

Location

Research Site

Madrid, Spain, 28040

Location

Research Site

Victoria, BC, Canada, V8R 6V5

Arms	Assigned Interventions
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.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted from 3 November 2021 and analyses presented in this results form are based on a data cut-off of 22 August 2023.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients who met the inclusion and none of the exclusion criteria were enrolled to the study. This study consisted of a screening period of 28 days. All the study assessments were performed as per schedule of assessment.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Participant Flow: Overall Study

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy
STARTED	16	4	10
COMPLETED	13	3	9
NOT COMPLETED	3	1	1
Patients ongoing treatment at data cut-off date of 22 August 2023.	3	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Safety analysis set included for baseline characteristics, and it included all patients who received any amount of study treatment.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Baseline Measures

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Total
Number of Participants [units: Participants]	16	4	10	30
Age Continuous [units: Years] Mean ± Standard Deviation	55.7 ± 12.07	66.8 ± 4.92	76.2 ± 9.72	64.0 ± 14.06
Sex: Female, Male [units: Participants]
Female	7	2	4	13
Male	9	2	6	17
Race/Ethnicity, Customized [units: Participants]
Asian	5	0	0	5
White	10	3	7	20
Other	0	1	1	2
Not reported	1	0	2	3
Race/Ethnicity, Customized [units: Participants]
Hispanic or Latino	3	0	0	3
Not Hispanic or Latino	12	4	5	21
Missing	0	0	4	4
Other	1	0	1	2

Outcome Measures

1. Primary Outcome Measure: Objective response rate [ Time Frame: First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months) ]

Measure Type	Primary
Measure Name	Objective response rate
Measure Description	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).
Time Frame	First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response evaluable analysis set included all patients, treated with study treatment, with measurable disease at baseline.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Measured Values

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy
Number of Participants Analyzed [units:participants]	16	3	10
Objective response rate [units: Percentage of Patients] Number (95% Confidence Interval)	18.8 (4.0 to 45.6)	33.3 (0.8 to 90.6)	30.0 (6.7 to 65.2)

No statistical analysis provided for Objective response rate

2. Secondary Outcome Measure: Duration of response [ Time Frame: First documented response until date of documented progression or data-cut off date (21.6 Months) ]

Measure Type	Secondary
Measure Name	Duration of response
Measure Description	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.
Time Frame	First documented response until date of documented progression or data-cut off date (21.6 Months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response evaluable analysis set included all patients, treated with study treatment, with measurable disease at baseline.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Measured Values

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy
Number of Participants Analyzed [units:participants]	3	1	3
Duration of response [units: Months] Median (95% Confidence Interval)	1.9 (1.7 to NA) ^[1]	NA (NA to NA) ^[1]	1.9 (NA to NA) ^[1]

No statistical analysis provided for Duration of response

3. Secondary Outcome Measure: Progression-free survival [ Time Frame: First dose until documented disease progression or data cut-off date (21.6 Months) ]

Measure Type	Secondary
Measure Name	Progression-free survival
Measure Description	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.
Time Frame	First dose until documented disease progression or data cut-off date (21.6 Months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all patients who received any amount of study treatment.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Measured Values

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy
Number of Participants Analyzed [units:participants]	16	4	10
Progression-free survival [units: Months] Median (95% Confidence Interval)	5.4 (3.4 to NA) ^[1]	NA (1.4 to NA) ^[1]	1.9 (0.9 to NA) ^[1]

No statistical analysis provided for Progression-free survival

4. Secondary Outcome Measure: Overall survival (OS) [ Time Frame: First dose until data cut-off date (21.6 Months) ]

Measure Type	Secondary
Measure Name	Overall survival (OS)
Measure Description	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.
Time Frame	First dose until data cut-off date (21.6 Months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all patients who received any amount of study treatment.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Measured Values

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy
Number of Participants Analyzed [units:participants]	16	4	10
Overall survival (OS) [units: Months] Median (95% Confidence Interval)	NA (NA to NA) ^[1]	NA (1.4 to NA) ^[1]	NA (2.0 to NA) ^[1]

No statistical analysis provided for Overall survival (OS)

5. Secondary Outcome Measure: Number of patients with adverse events and serious adverse events [ Time Frame: 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]) ]

Measure Type	Secondary
Measure Name	Number of patients with adverse events and serious adverse events
Measure Description	The safety and tolerability of the capivasertib treatment in each Cohort was assessed.
Time Frame	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])
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all patients who received any amount of study treatment.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Measured Values

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy
Number of Participants Analyzed [units:participants]	16	4	10
Number of patients with adverse events and serious adverse events [units: Participants]
Any adverse event (AE)	16	3	10
Any AE possibly related to treatment	14	3	8
Any AE of CTCAE grade 3 or higher	7	1	7
Any AE of CTCAE grade 3 or higher, possibly related to treatment	3	1	5
Any AE with outcome = death	0	0	0
Any AE with outcome = death, possibly related to treatment	0	0	0
Any SAE (including events with outcome = death)	2	0	3
Any SAE (including events with outcome = death), possibly related to treatment	0	0	3

No statistical analysis provided for Number of patients with adverse events and serious adverse events

6. Secondary Outcome Measure: Plasma concentration of capivasertib overtime [ Time Frame: 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) ]

Measure Type	Secondary
Measure Name	Plasma concentration of capivasertib overtime
Measure Description	The plasma concentration of capivasertib when administered in patients in each Cohort was determined.
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) analysis set included all patients who received at least 1 dose of capivasertib, for whom there is at least 1 reportable PK concentration.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Measured Values

	Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy
Number of Participants Analyzed [units:participants]	16	4	9
Plasma concentration of capivasertib overtime [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Cycle 1 Day 1 (Post-dose [1 hour])	394.9 (157.0%)	414.4 (125.7%)	287.1 (676.2%)
Cycle 1 Day 1 (Post-dose [2 hours])	883.7 (59.12%)	962.9 (40.33%)	976.1 (58.27%)
Cycle 1 Day 1 (Post-dose [4 hours])	528.5 (49.28%)	677.2 (65.77%)	780.1 (56.99%)
Cycle 1 Day 8 (Pre-dose)	6.149 (207.4%)	8.477 (103.9%)	14.31 (138.8%)
Cycle 1 Day 15 (Pre-dose)	5.844 (146.1%)	9.245 (73.63%)	32.36 (373.5%)
Cycle 1 Day 22 (Pre-dose)	7.974 (372.2%)	NA (NA%)^[1]	NA (NA%)^[1]

No statistical analysis provided for Plasma concentration of capivasertib overtime

Serious Adverse Events

Time Frame	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])
Additional Description	No text entered.

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Serious Adverse Events

Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy

Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy

Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy

Total, serious adverse events

# participants affected / at risk

2/16 (12.50%)

0/4 (0.00%)

3/10 (30.00%)

Infections and infestations

COVID-19 pneumonia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Infections and infestations

Perirectal abscess¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Respiratory, thoracic and mediastinal disorders

Obliterative bronchiolitis¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Skin and subcutaneous tissue disorders

Erythema multiforme¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.0

Other Adverse Events

Time Frame	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])
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy	Patients with R/R FL received capivasertib 480 mg orally until progression of disease (PD) or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy	Patients with R/R MZL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.
Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy	Patients with R/R MCL received capivasertib 480 mg orally until PD or unacceptable toxicity, or if the patient/investigator requests to stop the treatment.

Other Adverse Events

Relapsed or refractory Follicular Lymphoma (R/R FL): Capivasertib monotherapy

Relapsed or refractory Marginal zone lymphoma (R/R MZL): Capivasertib monotherapy

Relapsed or refractory Mantle cell lymphoma (R/R MCL): Capivasertib monotherapy

Total, other (not including serious) adverse events

# participants affected / at risk

16/16 (100.00%)

3/4 (75.00%)

9/10 (90.00%)

Infections and infestations

COVID-19¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

1/10 (10.00%)

# events

Infections and infestations

Cystitis¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Infections and infestations

Herpes zoster¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Infections and infestations

Respiratory tract infection¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

0/10 (0.00%)

# events

Infections and infestations

Respiratory tract infection viral¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

3/16 (18.75%)

0/4 (0.00%)

0/10 (0.00%)

# events

Infections and infestations

Wound abscess¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Infections and infestations

Escherichia urinary tract infection¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

1/16 (6.25%)

1/4 (25.00%)

0/10 (0.00%)

# events

Blood and lymphatic system disorders

Lymphocytosis¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹

# participants affected / at risk

3/16 (18.75%)

0/4 (0.00%)

0/10 (0.00%)

# events

Blood and lymphatic system disorders

Neutrophilia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

1/10 (10.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

2/16 (12.50%)

1/4 (25.00%)

1/10 (10.00%)

# events

Metabolism and nutrition disorders

Dehydration¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Metabolism and nutrition disorders

Glucose tolerance impaired¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Metabolism and nutrition disorders

Hypercalcaemia¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

2/10 (20.00%)

# events

Metabolism and nutrition disorders

Hyperuricaemia¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

2/10 (20.00%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Metabolism and nutrition disorders

Hypophosphataemia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

1/10 (10.00%)

# events

Psychiatric disorders

Anxiety¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Nervous system disorders

Ageusia¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Nervous system disorders

Anosmia¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Nervous system disorders

Dizziness¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

1/10 (10.00%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

3/16 (18.75%)

1/4 (25.00%)

0/10 (0.00%)

# events

Nervous system disorders

Memory impairment¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Eye disorders

Ocular discomfort¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Ear and labyrinth disorders

Vertigo¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

0/10 (0.00%)

# events

Vascular disorders

Haemorrhage¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Vascular disorders

Orthostatic hypotension¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

1/10 (10.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

1/10 (10.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹

# participants affected / at risk

2/16 (12.50%)

0/4 (0.00%)

0/10 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Upper-airway cough syndrome¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Gastrointestinal disorders

Dental caries¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

15/16 (93.75%)

2/4 (50.00%)

4/10 (40.00%)

# events

Gastrointestinal disorders

Dry mouth¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Gastrointestinal disorders

Flatulence¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

1/10 (10.00%)

# events

Gastrointestinal disorders

Haemorrhoids¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Gastrointestinal disorders

Intussusception¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

2/16 (12.50%)

2/4 (50.00%)

5/10 (50.00%)

# events

Gastrointestinal disorders

Odynophagia¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Gastrointestinal disorders

Proctalgia¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Gastrointestinal disorders

Stomatitis¹

# participants affected / at risk

1/16 (6.25%)

1/4 (25.00%)

0/10 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

2/16 (12.50%)

1/4 (25.00%)

1/10 (10.00%)

# events

Hepatobiliary disorders

Cholestasis¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

0/10 (0.00%)

# events

Hepatobiliary disorders

Hypertransaminasaemia¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

0/10 (0.00%)

# events

Skin and subcutaneous tissue disorders

Hyperhidrosis¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

0/10 (0.00%)

# events

Skin and subcutaneous tissue disorders

Night sweats¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

2/16 (12.50%)

0/4 (0.00%)

3/10 (30.00%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹

# participants affected / at risk

2/16 (12.50%)

0/4 (0.00%)

0/10 (0.00%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

0/10 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹

# participants affected / at risk

2/16 (12.50%)

1/4 (25.00%)

0/10 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal discomfort¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Renal and urinary disorders

Renal impairment¹

# participants affected / at risk

1/16 (6.25%)

1/4 (25.00%)

0/10 (0.00%)

# events

General disorders

Asthenia¹

# participants affected / at risk

1/16 (6.25%)

1/4 (25.00%)

1/10 (10.00%)

# events

General disorders

Fatigue¹

# participants affected / at risk

3/16 (18.75%)

0/4 (0.00%)

2/10 (20.00%)

# events

General disorders

Oedema peripheral¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

General disorders

Pain¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

General disorders

Peripheral swelling¹

# participants affected / at risk

0/16 (0.00%)

1/4 (25.00%)

0/10 (0.00%)

# events

General disorders

Pyrexia¹

# participants affected / at risk

1/16 (6.25%)

1/4 (25.00%)

2/10 (20.00%)

# events

Investigations

Blood creatinine increased¹

# participants affected / at risk

2/16 (12.50%)

0/4 (0.00%)

1/10 (10.00%)

# events

Investigations

Blood lactate dehydrogenase increased¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

1/10 (10.00%)

# events

Investigations

Blood thyroid stimulating hormone increased¹

# participants affected / at risk

1/16 (6.25%)

0/4 (0.00%)

0/10 (0.00%)

# events

Investigations

Electrocardiogram QT prolonged¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Investigations

Neutrophil count decreased¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Investigations

Weight decreased¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

Injury, poisoning and procedural complications

Contusion¹

# participants affected / at risk

0/16 (0.00%)

0/4 (0.00%)

1/10 (10.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.0

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
Redacted Statistical Analysis Plan
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Redacted Clinical Study Protocol
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Redacted CSR synopsis
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Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Redacted Statistical Analysis Plan

Redacted Clinical Study Protocol

Redacted CSR synopsis

Trial Results Summaries