Breast Cancer
Conditions
Keywords
Breast cancer, PM01183, lurbinectedin, Pharma Mar
Brief summary
A Clinical Trial of PM01183 in Metastatic Breast Cancer to assess the antitumor activity of PM01183 ,to evaluate whether the presence of a known germline mutation in BRCA 1/2 predicts response to PM01183 in Metastatic Breast Cancer (MBC) patients, to evaluate the safety profile of this PM01183 to analyze the pharmacokinetics (PK) and PK/PD (pharmacokinetic/pharmacodynamic) correlations and to evaluate the pharmacogenomic (PGx) expression profile in tumor samples.
Detailed description
A Multicenter Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer to assess the antitumor activity of PM01183 in terms of overall response rate (ORR), duration of response (DR),clinical benefit \[ORR or stable disease lasting over three months (SD \> 3 months)\], progression free survival (PFS), and one-year overall survival (1y-OS) and to evaluate whether the presence of a known germline mutation in BRCA 1/2 predicts response to PM01183 in MBC patients, to explore the activity of PM01183 in specific breast cancer subpopulations according to hormonal receptor status, HER-2 overexpression, number and/or type of prior therapies, or according to other available histological/molecular classifications, to evaluate the safety profile of this PM01183 administration schedule \[Day 1 every three weeks (q3wk)\] in this patient population, to analyze the pharmacokinetics (PK) of PM01183 in this patient population, to explore PK/PD (pharmacokinetic/ pharmacodynamic) correlations, if applicable and to evaluate the pharmacogenomic (PGx) expression profile of selected putative markers potentially predictive of response to PM01183, in tissues from tumor samples.
Interventions
DRUGPM01183
PM01183 drug product (DP) is presented as a lyophilized powder for concentrate for solution for infusion with two strengths: 1 mg/vial and 4 mg/vial
Sponsors
PharmaMar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Women ≥ 18 and ≤ 75 years of age. * Voluntary signed informed consent form (ICF). * Proven diagnosis of metastatic breast cancer (MBC). * At least one, but no more than three, prior chemotherapy regimens for MBC. * Patients with known HER-2 overexpressing MBC must have failed at least one prior trastuzumab-containing regimen for metastatic disease. * Disease evaluable for response by specific appropriate criteria. * No or minimal disease-related symptoms not affecting patient daily activities. * Adequate major organ function (normal or minimal alteration in liver, kidney, hematological, metabolic and cardiac function) * Wash out periods prior to Day 1 of Cycle 1: At least three weeks since the last chemotherapy (six weeks in some particular cases) and At least four weeks since the last radiotherapy (RT) \> 30 Gy) and At least one week since the last hormonal therapy and At least two weeks since the last biological/investigational therapy * Minimal or no ongoing toxicity from immediately prior therapy according to specific appropriate criteria. Mild ongoing toxicity is allowed in case of alopecia, skin toxicity, fatigue and/or finger numbness or tumbling. * Patients of child-bearing potential must agree to use a medically approved contraception method until at least six weeks after the last study drug administration. * Known deleterious germline mutation of BRCA1/2 (Patients in Cohorts A and A1) * Prior treatment with PARP inhibitors (Patients in Cohort A1)
Exclusion criteria
* Prior treatment with PM01183 or trabectedin. * Extensive prior RT. * Prior or concurrent malignant disease unless cured for more than five years. * Exceptions are breast cancer in the other breast. * Uncommon or rare subtypes of breast cancer. * Symptomatic or progressive brain metastases. * Bone-limited and exclusively metastases. * Relevant diseases or clinical situations which may increase patient's risk: History of cardiac disease. Moderate breathing difficulties or oxygen requirement Active uncontrolled infection. Unhealed wound or presence of any external drainage. Chronically active viral hepatitis. Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV). Known muscular disease or functional alteration * Pregnant or breastfeeding women. * Impending need for immediate RT for symptomatic relief. * Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment | The overall response rate is defined as the percentage of patients with a confirmed response, either complete response (CR) or partial response (PR), according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; PR \>=30% decrease in the sum of the longest diameter of target lesions. |
| Overall Response | Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment | Overall Response Rate (ORR) in the population evaluable for efficacy according to RECIST v.1.1. ORR was defined as the percentage of patients with a confirmed response, either CR or PR, according to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions; SD, stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; TF, treatment failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response Rate at 12 Months | Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 12 months | Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions. |
| Clinical Benefit Rate | Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment | Clinical benefit, defined as the percentage of patients with ORR or SD lasting over three months (SD \>3 months). The overall response rate is defined as the percentage of patients with a confirmed response, either complete response (CR) or partial response (PR), according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; PR \>=30% decrease in the sum of the longest diameter of target lesions. SD, stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Progression-free Survival (PFS) | 36 months | Progression-free survival (PFS) is defined as the period of time from the date of first infusion to the date of progression disease, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Progression-free Survival at 3 Months | Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 3 months | Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Duration of Response | Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment | Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions. |
| Progression-free Survival at 12 Months | Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 12 months | Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Overall Survival (OS) | 36 months | Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact |
| Overall Survival Rate at 12 Months | Time from the date of first infusion to the date of death or last contact, up to 12 months | Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact |
| Overall Survival Rate at 18 Months | Time from the date of first infusion to the date of death or last contact, up to 18 months | Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact. |
| Progression-free Survival at 6 Months | Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 6 months | Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Duration of Response Rate at 6 Months | Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 6 months | Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions. |
Countries
Spain, United States
Participant flow
Recruitment details
The first patient was included on 27JUN12 and the first study treatment administration was on 28JUN12. The cutoff date for the results was 24OCT18. A total of 111 patients were included in the 3 cohorts of the study: 56 in Cohort A (BRCA+), 20 in Cohort A1 (BRCA+/PARPi), 35 in Cohort B (Unselected).
Participants by arm
| Arm | Count |
|---|---|
| Cohort A (BRCA+) Patients with known deleterious BRCA1/2 mutation status at study entry | 56 |
| Cohort A1 (BRCA+/PARPi) Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 20 |
| Cohort B (Unselected) Patients without known deleterious BRCA1/2 mutation status at study entry, i.e., either:
* Patients known to have no deleterious BRCA1/2 mutations (BRCA-), or
* Patients whose BRCA 1/2 mutation status was unknown (BRCA-UK). BRCA1/2 germline mutation status would be assessed in all patients in this subgroup responding to lurbinectedin treatment. | 35 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 2 |
| Overall Study | Never treated | 2 | 0 | 0 |
| Overall Study | Non-treatment-related AE | 1 | 0 | 0 |
| Overall Study | Other reasons | 0 | 1 | 0 |
| Overall Study | Physician Decision | 4 | 2 | 2 |
| Overall Study | Progressive disease | 48 | 15 | 29 |
| Overall Study | Treatment-related AE | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 5 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 100 Participants | 51 Participants | 19 Participants | 30 Participants |
| Age, Continuous | 45.0 years | 42.5 years | 45.0 years | 52.0 years |
| Albumin | 4.1 g/dL | 4.1 g/dL | 4.1 g/dL | 4.0 g/dL |
| Body Surface Area | 1.72 m^2 | 1.72 m^2 | 1.63 m^2 | 1.75 m^2 |
| BRCA deleterious mutation Both | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| BRCA deleterious mutation BRCA1 | 43 Participants | 33 Participants | 10 Participants | 0 Participants |
| BRCA deleterious mutation BRCA2 | 32 Participants | 23 Participants | 9 Participants | 0 Participants |
| BRCA deleterious mutation Not applicable | 35 Participants | 0 Participants | 0 Participants | 35 Participants |
| ECOG PS PS 0 | 64 Participants | 32 Participants | 10 Participants | 22 Participants |
| ECOG PS PS 1 | 47 Participants | 24 Participants | 10 Participants | 13 Participants |
| Height | 162.0 cm | 162.5 cm | 161.0 cm | 161.0 cm |
| Histology grade at diagnosis Moderately differentiated | 31 Participants | 10 Participants | 8 Participants | 13 Participants |
| Histology grade at diagnosis Poorly differentiated | 59 Participants | 31 Participants | 11 Participants | 17 Participants |
| Histology grade at diagnosis Unknown | 17 Participants | 12 Participants | 1 Participants | 4 Participants |
| Histology grade at diagnosis Well differentiated | 4 Participants | 3 Participants | 0 Participants | 1 Participants |
| Histology type at diagnosis Ductal carcinoma | 108 Participants | 54 Participants | 20 Participants | 34 Participants |
| Histology type at diagnosis Lobular and ductal carcinoma | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Histology type at diagnosis Lobular carcinoma | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Hormonal status ER and/or PR positive and HER2 negative | 47 Participants | 21 Participants | 12 Participants | 14 Participants |
| Hormonal status ER and/or PR positive and HER2 positive | 6 Participants | 2 Participants | 1 Participants | 3 Participants |
| Hormonal status ER and PR negative and HER2 positive | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Hormonal status Triple negative | 57 Participants | 33 Participants | 7 Participants | 17 Participants |
| Number of sites at baseline | 3.0 sites | 3.0 sites | 3.0 sites | 2.0 sites |
| Prior radiotherapy | 94 Participants | 44 Participants | 18 Participants | 32 Participants |
| Prior surgery | 106 Participants | 53 Participants | 19 Participants | 34 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Caucasian | 98 Participants | 50 Participants | 16 Participants | 32 Participants |
| Race/Ethnicity, Customized Race Hispanic | 5 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Unknown | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Spain | 51 participants | 21 participants | 4 participants | 26 participants |
| Region of Enrollment United States | 60 participants | 35 participants | 16 participants | 9 participants |
| Sex: Female, Male Female | 111 Participants | 56 Participants | 20 Participants | 35 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sites at baseline <3 sites | 51 Participants | 23 Participants | 7 Participants | 21 Participants |
| Sites at baseline ≥3 sites | 60 Participants | 33 Participants | 13 Participants | 14 Participants |
| Sites of disease at diagnosis Bilateral | 4 Participants | 2 Participants | 0 Participants | 2 Participants |
| Sites of disease at diagnosis Left breast | 55 Participants | 26 Participants | 11 Participants | 18 Participants |
| Sites of disease at diagnosis Right breast | 52 Participants | 28 Participants | 9 Participants | 15 Participants |
| Stage at diagnosis Stage I | 12 Participants | 9 Participants | 3 Participants | 0 Participants |
| Stage at diagnosis Stage II | 48 Participants | 26 Participants | 9 Participants | 13 Participants |
| Stage at diagnosis Stage III | 41 Participants | 16 Participants | 6 Participants | 19 Participants |
| Stage at diagnosis Stage IV | 10 Participants | 5 Participants | 2 Participants | 3 Participants |
| Time from first diagnosis to registration | 46.5 months | 44.0 months | 55.7 months | 47.0 months |
| Time from last progression before study entry | 3.0 weeks | 2.9 weeks | 3.2 weeks | 3.0 weeks |
| Time from metastatic disease to registration | 14.8 months | 12.5 months | 26.1 months | 13.8 months |
| Weight | 68.1 Kg | 69.2 Kg | 59.8 Kg | 71.7 Kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 40 / 54 | 13 / 20 | 30 / 35 |
| other Total, other adverse events | 54 / 54 | 20 / 20 | 34 / 35 |
| serious Total, serious adverse events | 14 / 54 | 5 / 20 | 8 / 35 |
Outcome results
Primary
Overall Response
Overall Response Rate (ORR) in the population evaluable for efficacy according to RECIST v.1.1. ORR was defined as the percentage of patients with a confirmed response, either CR or PR, according to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions; SD, stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; TF, treatment failure.
Time frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A (BRCA+) | Overall Response | PR | 20 Participants |
| Cohort A (BRCA+) | Overall Response | SD | 24 Participants |
| Cohort A (BRCA+) | Overall Response | CR | 2 Participants |
| Cohort A (BRCA+) | Overall Response | TF | 0 Participants |
| Cohort A (BRCA+) | Overall Response | PD | 8 Participants |
| Cohort A1 (BRCA+/PARPi) | Overall Response | PR | 1 Participants |
| Cohort A1 (BRCA+/PARPi) | Overall Response | CR | 0 Participants |
| Cohort A1 (BRCA+/PARPi) | Overall Response | SD | 9 Participants |
| Cohort A1 (BRCA+/PARPi) | Overall Response | PD | 10 Participants |
| Cohort A1 (BRCA+/PARPi) | Overall Response | TF | 0 Participants |
| Cohort B (Unselected) | Overall Response | TF | 1 Participants |
| Cohort B (Unselected) | Overall Response | PD | 13 Participants |
| Cohort B (Unselected) | Overall Response | PR | 3 Participants |
| Cohort B (Unselected) | Overall Response | SD | 17 Participants |
| Cohort B (Unselected) | Overall Response | CR | 0 Participants |
Primary
Overall Response Rate (ORR)
The overall response rate is defined as the percentage of patients with a confirmed response, either complete response (CR) or partial response (PR), according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; PR \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Overall Response Rate (ORR) | 40.7 percentage |
| Cohort A1 (BRCA+/PARPi) | Overall Response Rate (ORR) | 5.0 percentage |
| Cohort B (Unselected) | Overall Response Rate (ORR) | 8.8 percentage |
Secondary
Clinical Benefit Rate
Clinical benefit, defined as the percentage of patients with ORR or SD lasting over three months (SD \>3 months). The overall response rate is defined as the percentage of patients with a confirmed response, either complete response (CR) or partial response (PR), according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; PR \>=30% decrease in the sum of the longest diameter of target lesions. SD, stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Clinical Benefit Rate | 61.1 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Clinical Benefit Rate | 40.0 percentage of participants |
| Cohort B (Unselected) | Clinical Benefit Rate | 32.4 percentage of participants |
Secondary
Duration of Response
Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: Minimum 10-12 months if negative results and up to 26-28 months if study is to be complete the targeted enrollment
Population: Responder patients (PR or CR, whichever was first reached)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A (BRCA+) | Duration of Response | 6.3 months |
| Cohort A1 (BRCA+/PARPi) | Duration of Response | 2.7 months |
| Cohort B (Unselected) | Duration of Response | 3.6 months |
p-value: 0.0909Log Rank
Secondary
Duration of Response Rate at 12 Months
Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 12 months
Population: Responder patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Duration of Response Rate at 12 Months | 33.8 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Duration of Response Rate at 12 Months | 0 percentage of participants |
| Cohort B (Unselected) | Duration of Response Rate at 12 Months | 33.3 percentage of participants |
Secondary
Duration of Response Rate at 6 Months
Duration of response (DoR), defined as the time between the date when the response criteria (PR or CR, whichever was first reached) were fulfilled to the first date when disease progression (PD), recurrence or death was documented. According to the RECIST v.1.1 for target lesions and assessed by MRI: CR, complete response: Disappearance of all target lesions; PD, progressive disease: 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR, partial response: \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: Time between the response criteria date and the date when disease progression, recurrence or death was documented, up to 6 months
Population: Responder patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Duration of Response Rate at 6 Months | 53.1 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Duration of Response Rate at 6 Months | 0 percentage of participants |
| Cohort B (Unselected) | Duration of Response Rate at 6 Months | 33.3 percentage of participants |
Secondary
Overall Survival (OS)
Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact
Time frame: 36 months
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A (BRCA+) | Overall Survival (OS) | 18.6 months |
| Cohort A1 (BRCA+/PARPi) | Overall Survival (OS) | 8.1 months |
| Cohort B (Unselected) | Overall Survival (OS) | 12.1 months |
p-value: 0.0561Log Rank
Secondary
Overall Survival Rate at 12 Months
Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact
Time frame: Time from the date of first infusion to the date of death or last contact, up to 12 months
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Overall Survival Rate at 12 Months | 62.5 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Overall Survival Rate at 12 Months | 29.7 percentage of participants |
| Cohort B (Unselected) | Overall Survival Rate at 12 Months | 55.4 percentage of participants |
Secondary
Overall Survival Rate at 18 Months
Overall survival (OS), defined as the time from the date of first infusion to the date of death or last contact.
Time frame: Time from the date of first infusion to the date of death or last contact, up to 18 months
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Overall Survival Rate at 18 Months | 53.4 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Overall Survival Rate at 18 Months | 22.3 percentage of participants |
| Cohort B (Unselected) | Overall Survival Rate at 18 Months | 27.7 percentage of participants |
Secondary
Progression-free Survival at 12 Months
Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 12 months
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Progression-free Survival at 12 Months | 20.5 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Progression-free Survival at 12 Months | 0 percentage of participants |
| Cohort B (Unselected) | Progression-free Survival at 12 Months | 3.7 percentage of participants |
Secondary
Progression-free Survival at 3 Months
Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 3 months
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Progression-free Survival at 3 Months | 63.5 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Progression-free Survival at 3 Months | 42.5 percentage of participants |
| Cohort B (Unselected) | Progression-free Survival at 3 Months | 35.5 percentage of participants |
Secondary
Progression-free Survival at 6 Months
Progression-free survival (PFS), defined as the period of time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Time from the date of first infusion to the date of PD, death (due to any cause), or last tumor evaluation, up to 6 months
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (BRCA+) | Progression-free Survival at 6 Months | 37.6 percentage of participants |
| Cohort A1 (BRCA+/PARPi) | Progression-free Survival at 6 Months | 21.3 percentage of participants |
| Cohort B (Unselected) | Progression-free Survival at 6 Months | 11.1 percentage of participants |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the period of time from the date of first infusion to the date of progression disease, death (due to any cause), or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 36 months
Population: Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A (BRCA+) | Progression-free Survival (PFS) | 4.6 months |
| Cohort A1 (BRCA+/PARPi) | Progression-free Survival (PFS) | 1.4 months |
| Cohort B (Unselected) | Progression-free Survival (PFS) | 2.5 months |
p-value: 0.002Log Rank