Trial Outcomes & Findings for Study of Capivasertib in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NCT NCT05008055)

Last Updated: 2024-12-20

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months)

Results posted on

2024-12-20

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	16	4	10
Overall Study COMPLETED	13	3	9
Overall Study NOT COMPLETED	3	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Patients ongoing treatment at data cut-off date of 22 August 2023.	3	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=16 Participants 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 n=4 Participants 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 n=10 Participants 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.	Total n=30 Participants Total of all reporting groups
Age, Continuous	55.7 Years STANDARD_DEVIATION 12.07 • n=5 Participants	66.8 Years STANDARD_DEVIATION 4.92 • n=7 Participants	76.2 Years STANDARD_DEVIATION 9.72 • n=5 Participants	64.0 Years STANDARD_DEVIATION 14.06 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized White	10 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	20 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	12 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months)

Population: Response evaluable analysis set included all patients, treated with study treatment, with measurable disease at baseline.

Outcome measures

Outcome measures
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=16 Participants 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 n=3 Participants 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 n=10 Participants 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.
Objective Response Rate	18.8 Percentage of Patients Interval 4.0 to 45.6	33.3 Percentage of Patients Interval 0.8 to 90.6	30.0 Percentage of Patients Interval 6.7 to 65.2

SECONDARY outcome

Timeframe: First documented response until date of documented progression or data-cut off date (21.6 Months)

Population: Response evaluable analysis set included all patients, treated with study treatment, with measurable disease at baseline.

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.

Outcome measures

Outcome measures
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=3 Participants 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 n=1 Participants 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 n=3 Participants 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.
Duration of Response	1.9 Months Interval 1.7 to The values were not calculable due to low number of patients.	NA Months The values were not calculable due to low number of patients.	1.9 Months The values were not calculable due to low number of patients.

SECONDARY outcome

Timeframe: First dose until documented disease progression or data cut-off date (21.6 Months)

Population: Safety analysis set included all patients who received any amount of study treatment.

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.

Outcome measures

Outcome measures
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=16 Participants 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 n=4 Participants 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 n=10 Participants 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.
Progression-free Survival	5.4 Months Interval 3.4 to The upper limit of the 95% confidence interval (CI) was not reached due to the insufficient number of patients with events, and the short duration of follow-up.	NA Months Interval 1.4 to The upper limit of the 95% CI was not reached due to the insufficient number of patients with events, and the short duration of follow-up.	1.9 Months Interval 0.9 to The upper limit of the 95% CI was not reached due to the insufficient number of patients with events, and the short duration of follow-up.

SECONDARY outcome

Timeframe: First dose until data cut-off date (21.6 Months)

Population: Safety analysis set included all patients who received any amount of study treatment.

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.

Outcome measures

Outcome measures
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=16 Participants 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 n=4 Participants 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 n=10 Participants 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.
Overall Survival (OS)	NA Months Median and 95% CI could not be calculated as no patients were seen to experience the event of interest due to short duration of follow-up.	NA Months Interval 1.4 to The median and upper limit of 95% CI could not be calculated as they were not reached.	NA Months Interval 2.0 to The median and upper limit of 95% CI could not be calculated as they were not reached.

SECONDARY outcome

Timeframe: 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])

Population: Safety analysis set included all patients who received any amount of study treatment.

The safety and tolerability of the capivasertib treatment in each Cohort was assessed.

Outcome measures

Outcome measures
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=16 Participants 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 n=4 Participants 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 n=10 Participants 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.
Number of Patients With Adverse Events and Serious Adverse Events Any adverse event (AE)	16 Participants	3 Participants	10 Participants
Number of Patients With Adverse Events and Serious Adverse Events Any AE possibly related to treatment	14 Participants	3 Participants	8 Participants
Number of Patients With Adverse Events and Serious Adverse Events Any AE of CTCAE grade 3 or higher	7 Participants	1 Participants	7 Participants
Number of Patients With Adverse Events and Serious Adverse Events Any AE of CTCAE grade 3 or higher, possibly related to treatment	3 Participants	1 Participants	5 Participants
Number of Patients With Adverse Events and Serious Adverse Events Any AE with outcome = death	0 Participants	0 Participants	0 Participants
Number of Patients With Adverse Events and Serious Adverse Events Any AE with outcome = death, possibly related to treatment	0 Participants	0 Participants	0 Participants
Number of Patients With Adverse Events and Serious Adverse Events Any SAE (including events with outcome = death)	2 Participants	0 Participants	3 Participants
Number of Patients With Adverse Events and Serious Adverse Events Any SAE (including events with outcome = death), possibly related to treatment	0 Participants	0 Participants	3 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

The plasma concentration of capivasertib when administered in patients in each Cohort was determined.

Outcome measures

Outcome measures
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=16 Participants 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 n=4 Participants 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 n=9 Participants 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.
Plasma Concentration of Capivasertib Overtime Cycle 1 Day 1 (Post-dose [1 hour])	394.9 ng/mL Geometric Coefficient of Variation 157.0	414.4 ng/mL Geometric Coefficient of Variation 125.7	287.1 ng/mL Geometric Coefficient of Variation 676.2
Plasma Concentration of Capivasertib Overtime Cycle 1 Day 1 (Post-dose [2 hours])	883.7 ng/mL Geometric Coefficient of Variation 59.12	962.9 ng/mL Geometric Coefficient of Variation 40.33	976.1 ng/mL Geometric Coefficient of Variation 58.27
Plasma Concentration of Capivasertib Overtime Cycle 1 Day 1 (Post-dose [4 hours])	528.5 ng/mL Geometric Coefficient of Variation 49.28	677.2 ng/mL Geometric Coefficient of Variation 65.77	780.1 ng/mL Geometric Coefficient of Variation 56.99
Plasma Concentration of Capivasertib Overtime Cycle 1 Day 8 (Pre-dose)	6.149 ng/mL Geometric Coefficient of Variation 207.4	8.477 ng/mL Geometric Coefficient of Variation 103.9	14.31 ng/mL Geometric Coefficient of Variation 138.8
Plasma Concentration of Capivasertib Overtime Cycle 1 Day 15 (Pre-dose)	5.844 ng/mL Geometric Coefficient of Variation 146.1	9.245 ng/mL Geometric Coefficient of Variation 73.63	32.36 ng/mL Geometric Coefficient of Variation 373.5
Plasma Concentration of Capivasertib Overtime Cycle 1 Day 22 (Pre-dose)	7.974 ng/mL Geometric Coefficient of Variation 372.2	NA ng/mL Geometric Coefficient of Variation NA Geometric mean was not quantified because in given time point, when less than or equal to 50% of the concentration values were not measurable or quantified.	NA ng/mL Geometric Coefficient of Variation NA Geometric mean was not quantified because in given time point, when less than or equal to 50% of the concentration values were not measurable or quantified.

Adverse Events

Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy

Serious events: 3 serious events

Other events: 9 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy n=16 participants at risk 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 n=4 participants at risk 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 n=10 participants at risk 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.
Infections and infestations COVID-19 pneumonia	6.2% 1/16 • Number of events 1 • 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])	0.00% 0/4 • 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])	0.00% 0/10 • 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])
Infections and infestations Perirectal abscess	0.00% 0/16 • 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])	0.00% 0/4 • 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])	10.0% 1/10 • Number of events 1 • 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])
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/16 • 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])	0.00% 0/4 • 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])	10.0% 1/10 • Number of events 1 • 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])
Respiratory, thoracic and mediastinal disorders Obliterative bronchiolitis	6.2% 1/16 • Number of events 1 • 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])	0.00% 0/4 • 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])	0.00% 0/10 • 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])
Gastrointestinal disorders Diarrhoea	0.00% 0/16 • 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])	0.00% 0/4 • 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])	10.0% 1/10 • Number of events 1 • 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])
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/16 • 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])	0.00% 0/4 • 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])	10.0% 1/10 • Number of events 1 • 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])

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
Publication restrictions are in place

Restriction type: OTHER