Classic Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma
Conditions
Brief summary
This is a phase 2 multi-cohort, un-controlled, non-randomized, open-label, multi-center study that assessed the antitumor activity and safety of non-alpha interleukin (IL-2) SAR444245 with or without other anticancer therapies in participants aged 12 years and older with relapsed or refractory B cell lymphoma. This study was structured as a master protocol with separate sub studies designed to investigate the use of SAR444245 either with or without other anticancer therapies for the treatment of relapsed or refractory B cell lymphoma. Substudy 1-Cohort A aimed to establish safety and preliminary anti-tumor activity for non-alpha interleukin (IL-2) SAR444245 combined with the anti-PD1 antibody, pembrolizumab in trial participants with classic Hodgkin lymphoma (cHL) who are anti-PD-(L)1-naive and have received at least 2 or 3 lines of systemic therapy. Substudy 3-Cohort C1 aims to establish safety and preliminary anti-tumor activity for SAR444245 as monotherapy in trial participants with diffuse large B-cell lymphoma (DLBCL). Trial participants in this study must have received at least 2 lines of systemic therapy and have either stable or progressive disease 1-3 months post Health Authority approved Chimeric Antigen Receptor T-cell (CAR-T) treatment when given as last systemic treatment prior to study enrollment.
Detailed description
The duration of the study for an individual participant started from the signature of the main informed consent and included: a screening period of up to 28 days; a treatment period \[max\] 35 cycles (21 days per cycle) for Cohort A and 52 cycles (14 days per cycle) for Cohort C1 or until occurrence of unacceptable toxicities or until PD; an end-of-treatment visit at least approximately 30 days following the last administration of study drug (or until the participant receives another anticancer therapy, whichever is earlier); and a follow-up visits 3 months after treatment discontinuation and every 3 months thereafter following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier.
Interventions
DRUGTHOR-707
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion
DRUGPembrolizumab
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion
Sponsors
Merck Sharp & Dohme LLC
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have been ≥ 12 years of age, at the time of signing the informed consent * Disease location was amenable to tumor biopsy at baseline * All participants must have had a measurable disease * Both male and female participants agreed to use approved contraception methods; not pregnant or breastfeeding for female participants; no donation or cryopreservation of eggs (ova, oocytes) for female participants and sperms for male participants. * Had to be capable of giving signed informed consent For cohort A: Histologically or cytologically confirmed diagnosis of classic Hodgkin lymphoma (cHL), must have received at least two prior lines of systemic therapy for cHL, including at least one containing an anthracycline or brentuximab. For cohort C1: Histologically confirmed diagnosis of diffuse large B Cell lymphoma (DLBCL), must have received at least two prior lines of systemic therapy for DLBCL, including one containing a combination of anthracycline and rituximab (or another anti-CD20 agent), with the last line of therapy a Health Authority approved CD19-directed CAR-T therapy. Patients must have BOR (Best Overall Response) of stable disease (SD) or progressive disease (PD) after CD-19 directed CAR-T therapy.
Exclusion criteria
Participants were excluded from the study if any of the following criteria applied: * Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 (≥ 16 years old). Lansky Scale (\< 16 years old) ≤ 60% * Poor bone marrow reserve * Poor organ function * Participants with baseline oxygen saturation (SpO2) ≤ 92% (without oxygen therapy) * Lymphomatous involvement of the central nervous system * History of allogenic or solid organ transplant * Prior IV or subcutaneous anticancer therapy, investigational agent, major surgery within 21 days prior to initiation of IMP; oral anticancer therapy within 5 half-lives or completed palliative radiotherapy within 21 days prior to initiation of IMP * Has received prior IL-2-based anticancer treatment * Comorbidity requiring corticosteroid therapy * Antibiotic use (excluding topical antibiotics) ≤ 14 days prior to first dose of IMP * Severe or unstable cardiac condition within 6 months prior to starting study treatment * Had active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years-Known second malignancy either progressing or requiring active treatment within the last 3 years * Receipt of a live or live attenuated virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines or SARS-CoV-2 vaccine that do not contain live virus were permitted The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | From first dose of study treatment administration (Day 1) up to approximately 21 months | The CRR was defined as the percentage of participants who had a complete response (CR) as the best overall response (BOR) as per Investigator assessment (Lugano response criteria 2014). The BOR was defined as the BOR observed from the date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurred first. CR based on computed tomography (CT)-based response: lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5 centimeter (cm) in longest transverse diameter of a lesion (LDi) and no extralymphatic sites of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 29 months | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened (according to the Investigator's opinion) or became serious during the TE period. |
| Number of Participants With Dose Limiting Toxicities (DLTs) | From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days) | Selected events that occurred during the DLT observation period were considered as DLT unless due to PD or to a cause obviously unrelated to pegenzileukin. Selected events included: grade 4 neutropenic fever, grade 4 thrombocytopenia associated with clinically significant bleeding that required clinical intervention, grade 3 or above alanine aminotransferase or aspartate aminotransferase in combination with a bilirubin \>2 × upper limit of normal with no evidence of cholestasis or another cause, such as viral infection or other drugs, grade 3 or above vascular leak syndrome, grade 3 or above hypotension, grade 3 or above cytokine release syndrome, grade 3 or above AE that did not resolve to grade \<=2 within 7 days of starting accepted standard of care medical management. |
| Time to Response (TTR) | From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months | The TTR was defined as the time from the first administration of study treatment to the first tumor assessment at which the overall response was recorded as PR or CR determined by Investigator (Lugano response criteria 2014). CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5 millimeter (mm) X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used. |
| Duration of Response (DoR) | From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months | The DoR was defined as the time from the first tumor assessment at which the overall response was recorded as PR or CR until PD determined by Investigator (Lugano response criteria 2014), or death from any cause, whichever occurred first. CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5 millimeter (mm) X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used. |
| Objective Response Rate (ORR) | From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months | ORR was defined as the percentage of the participants with CR or partial response (PR) as the BOR as per Investigator assessment (Lugano response criteria 2014). The BOR was defined as the BOR observed from the date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurs first. CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5 millimeter (mm) X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used. |
| Progression Free Survival (PFS) | From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months | The PFS was defined as the time from the date of first study treatment administration to the date of the first documented PD determined by Investigator (Lugano response criteria 2014), or death due to any cause. PFS (CT-based response): An individual node/lesion had to be abnormal with: LDi \>1.5 cm and increased by \>=50% from positron emission tomography nadir and an increase in LDi or shortest axis perpendicular to the LDi from nadir, 0.5cm for lesions \<=2 cm, 1.0cm for lesions\>2 cm. In the setting of splenomegaly, the splenic length must be increased by \>50% of the extent of its prior increase beyond baseline. If there was no prior splenomegaly, increase by at least 2 cm from baseline. For new lesions regrowth of previously resolved lesions: a new node \>1.5 cm in any axis, a new extranodal site\>1.0 cm in any axis. |
| Plasma Concentrations of Pegenzileukin | Cycle 1 Day 2, Cycle 1 Day 3 (each cycle is 21 days) | Blood samples were collected at specified timepoints for the assessment of plasma concentrations of pegenzileukin . |
| Concentration at End of Infusion (Ceoi) of Pegenzileukin | Cycles 1, 2, 4, 7, 10, 15 (each cycle is 21 days) | Blood samples were collected at specified timepoints for the assessment of Ceoi of pegenzileukin . |
| Number of Participants With Anti-Drug Antibodies (ADA) Against Pegenzileukin | From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 29 months | Blood samples were collected at specified timepoints to assess the presence of ADA against pegenzileukin . Treatment-emergent ADA was defined as at least one treatment-induced or treatment-boosted ADA. Treatment-induced ADA was defined as ADA that developed during the TE period and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that was boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA is presented. |
| Clinical Benefit Rate (CBR) | From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months | CBR was defined as percentage of participants with clinical benefit (CR or PR as BOR, or stable disease \[SD\] lasting at least 6 months) determined by Investigator per Lugano response criteria 2014. BOR was defined as BOR observed from date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurred first. CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in SPD of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5mm X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used. SD (CT-based response): \<50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extranodal sites; no criteria for PD met. |
Countries
Argentina, Chile, Spain
Participant flow
Recruitment details
This study was conducted at 7 centers (corresponds to number of sites which screened at least one participant) in 3 countries from 07 December 2021 to 26 October 2022. Out of 19 participants who were screened, 14 participants were enrolled in the study.
Pre-assignment details
The study was terminated based on strategic sponsor decision not driven by any safety concerns. The Cohort C1 was not initiated and no participants were enrolled. Note: Reason for not completed = Reason for permanent full intervention discontinuation.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab Participants with cHL who were anti-PD-L1-naïve and had received at least 2 or 3 lines of systemic therapy received pegenzileukin 24 μg/kg via IV infusion over 30 minutes on Day 1 of each cycle (each cycle is 21 days), along with pembrolizumab 200 mg via 30 minutes IV infusion on Day 1 of each 3-week treatment cycle (each cycle is 21 days) as 3/4L therapy, until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse event: Not related to COVID-19 | 4 |
| Overall Study | Progressive disease | 4 |
| Overall Study | Unspecified: Not related to Coronavirus Disease 2019 (COVID-19) | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab |
|---|---|
| Age, Continuous | 29.6 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 5 / 14 |
Outcome results
Primary
Complete Response Rate (CRR)
The CRR was defined as the percentage of participants who had a complete response (CR) as the best overall response (BOR) as per Investigator assessment (Lugano response criteria 2014). The BOR was defined as the BOR observed from the date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurred first. CR based on computed tomography (CT)-based response: lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5 centimeter (cm) in longest transverse diameter of a lesion (LDi) and no extralymphatic sites of disease.
Time frame: From first dose of study treatment administration (Day 1) up to approximately 21 months
Population: The efficacy population consisted of all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Complete Response Rate (CRR) | 71.4 percentage of participants |
Secondary
Clinical Benefit Rate (CBR)
CBR was defined as percentage of participants with clinical benefit (CR or PR as BOR, or stable disease \[SD\] lasting at least 6 months) determined by Investigator per Lugano response criteria 2014. BOR was defined as BOR observed from date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurred first. CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in SPD of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5mm X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used. SD (CT-based response): \<50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extranodal sites; no criteria for PD met.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months
Population: The efficacy population consisted of all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Clinical Benefit Rate (CBR) | 92.9 percentage of participants |
Secondary
Concentration at End of Infusion (Ceoi) of Pegenzileukin
Blood samples were collected at specified timepoints for the assessment of Ceoi of pegenzileukin .
Time frame: Cycles 1, 2, 4, 7, 10, 15 (each cycle is 21 days)
Population: The PK population consisted of all participants from the exposed population with at least one PK concentration available after the first dose of study treatment. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Concentration at End of Infusion (Ceoi) of Pegenzileukin | Cycle 1 | 438.2 ng/mL | Standard Deviation 238.6 |
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Concentration at End of Infusion (Ceoi) of Pegenzileukin | Cycle 2 | 405.4 ng/mL | Standard Deviation 255.6 |
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Concentration at End of Infusion (Ceoi) of Pegenzileukin | Cycle 4 | 435.2 ng/mL | Standard Deviation 173.9 |
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Concentration at End of Infusion (Ceoi) of Pegenzileukin | Cycle 7 | 594.7 ng/mL | Standard Deviation 208.4 |
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Concentration at End of Infusion (Ceoi) of Pegenzileukin | Cycle 10 | 596.3 ng/mL | Standard Deviation 181.3 |
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Concentration at End of Infusion (Ceoi) of Pegenzileukin | Cycle 15 | 325.0 ng/mL | — |
Secondary
Duration of Response (DoR)
The DoR was defined as the time from the first tumor assessment at which the overall response was recorded as PR or CR until PD determined by Investigator (Lugano response criteria 2014), or death from any cause, whichever occurred first. CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5 millimeter (mm) X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months
Population: The efficacy population consisted of all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment. Only participants with confirmed CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Duration of Response (DoR) | NA months |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) Against Pegenzileukin
Blood samples were collected at specified timepoints to assess the presence of ADA against pegenzileukin . Treatment-emergent ADA was defined as at least one treatment-induced or treatment-boosted ADA. Treatment-induced ADA was defined as ADA that developed during the TE period and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that was boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA is presented.
Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 29 months
Population: ADA population consisted of all participants from exposed population with at least one ADA result (positive, negative or inconclusive) after the first dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Number of Participants With Anti-Drug Antibodies (ADA) Against Pegenzileukin | 3 Participants |
Secondary
Number of Participants With Dose Limiting Toxicities (DLTs)
Selected events that occurred during the DLT observation period were considered as DLT unless due to PD or to a cause obviously unrelated to pegenzileukin. Selected events included: grade 4 neutropenic fever, grade 4 thrombocytopenia associated with clinically significant bleeding that required clinical intervention, grade 3 or above alanine aminotransferase or aspartate aminotransferase in combination with a bilirubin \>2 × upper limit of normal with no evidence of cholestasis or another cause, such as viral infection or other drugs, grade 3 or above vascular leak syndrome, grade 3 or above hypotension, grade 3 or above cytokine release syndrome, grade 3 or above AE that did not resolve to grade \<=2 within 7 days of starting accepted standard of care medical management.
Time frame: From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)
Population: DLT-evaluable population consisted of all exposed participants in safety run-in part who had been treated and observed for DLT observation period. Any participants who had experienced a DLT during DLT observation period were also DLT-evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened (according to the Investigator's opinion) or became serious during the TE period.
Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 29 months
Population: The exposed population consisted of all participants who had given their informed consent and received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 14 Participants |
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 5 Participants |
Secondary
Objective Response Rate (ORR)
ORR was defined as the percentage of the participants with CR or partial response (PR) as the BOR as per Investigator assessment (Lugano response criteria 2014). The BOR was defined as the BOR observed from the date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurs first. CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5 millimeter (mm) X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months
Population: The efficacy population consisted of all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Objective Response Rate (ORR) | 92.9 percentage of participants |
Secondary
Plasma Concentrations of Pegenzileukin
Blood samples were collected at specified timepoints for the assessment of plasma concentrations of pegenzileukin .
Time frame: Cycle 1 Day 2, Cycle 1 Day 3 (each cycle is 21 days)
Population: The pharmacokinetic (PK) population consisted of all participants from the exposed population with at least one PK concentration available after the first dose of study treatment. Only participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Plasma Concentrations of Pegenzileukin | Cycle 1 Day 2 | 191.7 nanogram/milliliter (ng/mL) | Standard Deviation 78.4 |
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Plasma Concentrations of Pegenzileukin | Cycle 1 Day 3 | 95.2 nanogram/milliliter (ng/mL) | Standard Deviation 75.8 |
Secondary
Progression Free Survival (PFS)
The PFS was defined as the time from the date of first study treatment administration to the date of the first documented PD determined by Investigator (Lugano response criteria 2014), or death due to any cause. PFS (CT-based response): An individual node/lesion had to be abnormal with: LDi \>1.5 cm and increased by \>=50% from positron emission tomography nadir and an increase in LDi or shortest axis perpendicular to the LDi from nadir, 0.5cm for lesions \<=2 cm, 1.0cm for lesions\>2 cm. In the setting of splenomegaly, the splenic length must be increased by \>50% of the extent of its prior increase beyond baseline. If there was no prior splenomegaly, increase by at least 2 cm from baseline. For new lesions regrowth of previously resolved lesions: a new node \>1.5 cm in any axis, a new extranodal site\>1.0 cm in any axis.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months
Population: The efficacy population consisted of all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Progression Free Survival (PFS) | NA months |
Secondary
Time to Response (TTR)
The TTR was defined as the time from the first administration of study treatment to the first tumor assessment at which the overall response was recorded as PR or CR determined by Investigator (Lugano response criteria 2014). CR (CT-based response): lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5cm in LDi and no extralymphatic sites of disease. PR (CT-based response): lymph nodes and extralymphatic sites with \>=50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of upto 6 target measurable nodes and extranodal sites. A lesion too small to measure on CT, 5 millimeter (mm) X 5mm used as default value. No longer visible, 0 X 0 mm. A node \>5mm X 5mm, but smaller than normal, actual measurement used.
Time frame: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months
Population: The efficacy population consisted of all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment. Only participants with confirmed CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab | Time to Response (TTR) | 2.0 months |