Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Conditions
Keywords
Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Capivasertib monotherapy
Brief summary
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).
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).
Interventions
DRUGCapivasertib
Capivasertib will be taken orally twice a day (BD) 4 days on/ 3 days off.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | First documented response until date of documented progression or data-cut off date (21.6 Months) | 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. |
| Progression-free Survival | First dose until documented disease progression or data cut-off date (21.6 Months) | 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. |
| Overall Survival (OS) | First dose until data cut-off date (21.6 Months) | 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. |
| Number of Patients With Adverse Events and Serious Adverse Events | 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]) | The safety and tolerability of the capivasertib treatment in each Cohort was assessed. |
| Plasma Concentration of Capivasertib Overtime | 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) | The plasma concentration of capivasertib when administered in patients in each Cohort was determined. |
Countries
Canada, Denmark, France, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
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
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 16 |
| 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. | 4 |
| 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. | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Patients ongoing treatment at data cut-off date of 22 August 2023. | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Total | Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy |
|---|---|---|---|---|
| Age, Continuous | 66.8 Years STANDARD_DEVIATION 4.92 | 64.0 Years STANDARD_DEVIATION 14.06 | 55.7 Years STANDARD_DEVIATION 12.07 | 76.2 Years STANDARD_DEVIATION 9.72 |
| Race/Ethnicity, Customized Asian | 0 Participants | 5 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 4 Participants | 21 Participants | 12 Participants | 5 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 20 Participants | 10 Participants | 7 Participants |
| Sex: Female, Male Female | 2 Participants | 13 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 17 Participants | 9 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 1 / 4 | 2 / 10 |
| other Total, other adverse events | 16 / 16 | 3 / 4 | 9 / 10 |
| serious Total, serious adverse events | 2 / 16 | 0 / 4 | 3 / 10 |
Outcome results
Primary
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).
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)
Population: Response evaluable analysis set included all patients, treated with study treatment, with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Objective Response Rate | 18.8 Percentage of Patients |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Objective Response Rate | 33.3 Percentage of Patients |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Objective Response Rate | 30.0 Percentage of Patients |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Duration of Response | 1.9 Months |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Duration of Response | NA Months |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Duration of Response | 1.9 Months |
Secondary
Number of Patients With Adverse Events and Serious Adverse Events
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])
Population: Safety analysis set included all patients who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE of CTCAE grade 3 or higher | 7 Participants |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE with outcome = death | 0 Participants |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE of CTCAE grade 3 or higher, possibly related to treatment | 3 Participants |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome = death), possibly related to treatment | 0 Participants |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE possibly related to treatment | 14 Participants |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome = death) | 2 Participants |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any adverse event (AE) | 16 Participants |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE with outcome = death, possibly related to treatment | 0 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE of CTCAE grade 3 or higher | 1 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any adverse event (AE) | 3 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome = death) | 0 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome = death), possibly related to treatment | 0 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE with outcome = death, possibly related to treatment | 0 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE of CTCAE grade 3 or higher, possibly related to treatment | 1 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE with outcome = death | 0 Participants |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE possibly related to treatment | 3 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome = death), possibly related to treatment | 3 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any adverse event (AE) | 10 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE possibly related to treatment | 8 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE of CTCAE grade 3 or higher | 7 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE of CTCAE grade 3 or higher, possibly related to treatment | 5 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE with outcome = death | 0 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any AE with outcome = death, possibly related to treatment | 0 Participants |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Number of Patients With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome = death) | 3 Participants |
Secondary
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.
Time frame: First dose until data cut-off date (21.6 Months)
Population: Safety analysis set included all patients who received any amount of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Overall Survival (OS) | NA Months |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Overall Survival (OS) | NA Months |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Overall Survival (OS) | NA Months |
Secondary
Plasma Concentration of Capivasertib Overtime
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)
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 15 (Pre-dose) | 5.844 ng/mL | Geometric Coefficient of Variation 146.1 |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [4 hours]) | 528.5 ng/mL | Geometric Coefficient of Variation 49.28 |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 22 (Pre-dose) | 7.974 ng/mL | Geometric Coefficient of Variation 372.2 |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [1 hour]) | 394.9 ng/mL | Geometric Coefficient of Variation 157 |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 8 (Pre-dose) | 6.149 ng/mL | Geometric Coefficient of Variation 207.4 |
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [2 hours]) | 883.7 ng/mL | Geometric Coefficient of Variation 59.12 |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 8 (Pre-dose) | 8.477 ng/mL | Geometric Coefficient of Variation 103.9 |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 15 (Pre-dose) | 9.245 ng/mL | Geometric Coefficient of Variation 73.63 |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [2 hours]) | 962.9 ng/mL | Geometric Coefficient of Variation 40.33 |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 22 (Pre-dose) | NA ng/mL | — |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [1 hour]) | 414.4 ng/mL | Geometric Coefficient of Variation 125.7 |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [4 hours]) | 677.2 ng/mL | Geometric Coefficient of Variation 65.77 |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 22 (Pre-dose) | NA ng/mL | — |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [1 hour]) | 287.1 ng/mL | Geometric Coefficient of Variation 676.2 |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [2 hours]) | 976.1 ng/mL | Geometric Coefficient of Variation 58.27 |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 1 (Post-dose [4 hours]) | 780.1 ng/mL | Geometric Coefficient of Variation 56.99 |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 8 (Pre-dose) | 14.31 ng/mL | Geometric Coefficient of Variation 138.8 |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Plasma Concentration of Capivasertib Overtime | Cycle 1 Day 15 (Pre-dose) | 32.36 ng/mL | Geometric Coefficient of Variation 373.5 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Relapsed or Refractory Follicular Lymphoma (R/R FL): Capivasertib Monotherapy | Progression-free Survival | 5.4 Months |
| Relapsed or Refractory Marginal Zone Lymphoma (R/R MZL): Capivasertib Monotherapy | Progression-free Survival | NA Months |
| Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL): Capivasertib Monotherapy | Progression-free Survival | 1.9 Months |