A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PM01183
|
Drug: PM01183
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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford Women's Cancer Center | Stanford | California | United States | 94305 |
| 2 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 3 | Weill Cornell Medical College - New York Presbyterian Hospital | New York | New York | United States | 10065 |
| 4 | Abramson Cancer Center - Hospital of the University of Pennsylvania at Perelman Center for Advanced Medicine | Philadelphia | Pennsylvania | United States | 19104 |
| 5 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 6 | Complexo Hospitalario Universitario A Coruña | A Coruna | A Coruña | Spain | 15006 |
| 7 | Complexo Hospitalario Universitario de Santiago | Santiago de Compostela | A Coruña | Spain | 15706 |
| 8 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | 08035 | |
| 9 | Hospital Clínico Universitario de Valencia | Valencia | Spain | 46010 |
Sponsors and Collaborators
- PharmaMar
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- PM1183-B-003-11
Study Results
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). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Period Title: Overall Study | |||
| STARTED | 56 | 20 | 35 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 56 | 20 | 35 |
Baseline Characteristics
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) | Total |
|---|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. | Total of all reporting groups |
| Overall Participants | 56 | 20 | 35 | 111 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
51
91.1%
|
19
95%
|
30
85.7%
|
100
90.1%
|
| >=65 years |
5
8.9%
|
1
5%
|
5
14.3%
|
11
9.9%
|
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
42.5
|
45.0
|
52.0
|
45.0
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
56
100%
|
20
100%
|
35
100%
|
111
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Caucasian |
50
89.3%
|
16
80%
|
32
91.4%
|
98
88.3%
|
| Black |
2
3.6%
|
0
0%
|
1
2.9%
|
3
2.7%
|
| Asian |
1
1.8%
|
1
5%
|
0
0%
|
2
1.8%
|
| Hispanic |
2
3.6%
|
1
5%
|
2
5.7%
|
5
4.5%
|
| Unknown |
1
1.8%
|
2
10%
|
0
0%
|
3
2.7%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
35
62.5%
|
16
80%
|
9
25.7%
|
60
54.1%
|
| Spain |
21
37.5%
|
4
20%
|
26
74.3%
|
51
45.9%
|
| ECOG PS (Count of Participants) | ||||
| PS 0 |
32
57.1%
|
10
50%
|
22
62.9%
|
64
57.7%
|
| PS 1 |
24
42.9%
|
10
50%
|
13
37.1%
|
47
42.3%
|
| Sites of disease at diagnosis (Count of Participants) | ||||
| Left breast |
26
46.4%
|
11
55%
|
18
51.4%
|
55
49.5%
|
| Right breast |
28
50%
|
9
45%
|
15
42.9%
|
52
46.8%
|
| Bilateral |
2
3.6%
|
0
0%
|
2
5.7%
|
4
3.6%
|
| Histology type at diagnosis (Count of Participants) | ||||
| Ductal carcinoma |
54
96.4%
|
20
100%
|
34
97.1%
|
108
97.3%
|
| Lobular carcinoma |
2
3.6%
|
0
0%
|
0
0%
|
2
1.8%
|
| Lobular and ductal carcinoma |
0
0%
|
0
0%
|
1
2.9%
|
1
0.9%
|
| Histology grade at diagnosis (Count of Participants) | ||||
| Well differentiated |
3
5.4%
|
0
0%
|
1
2.9%
|
4
3.6%
|
| Moderately differentiated |
10
17.9%
|
8
40%
|
13
37.1%
|
31
27.9%
|
| Poorly differentiated |
31
55.4%
|
11
55%
|
17
48.6%
|
59
53.2%
|
| Unknown |
12
21.4%
|
1
5%
|
4
11.4%
|
17
15.3%
|
| Stage at diagnosis (Count of Participants) | ||||
| Stage I |
9
16.1%
|
3
15%
|
0
0%
|
12
10.8%
|
| Stage II |
26
46.4%
|
9
45%
|
13
37.1%
|
48
43.2%
|
| Stage III |
16
28.6%
|
6
30%
|
19
54.3%
|
41
36.9%
|
| Stage IV |
5
8.9%
|
2
10%
|
3
8.6%
|
10
9%
|
| BRCA deleterious mutation (Count of Participants) | ||||
| BRCA1 |
33
58.9%
|
10
50%
|
0
0%
|
43
38.7%
|
| BRCA2 |
23
41.1%
|
9
45%
|
0
0%
|
32
28.8%
|
| Both |
0
0%
|
1
5%
|
0
0%
|
1
0.9%
|
| Not applicable |
0
0%
|
0
0%
|
35
100%
|
35
31.5%
|
| Hormonal status (Count of Participants) | ||||
| Triple negative |
33
58.9%
|
7
35%
|
17
48.6%
|
57
51.4%
|
| ER and/or PR positive and HER2 negative |
21
37.5%
|
12
60%
|
14
40%
|
47
42.3%
|
| ER and/or PR positive and HER2 positive |
2
3.6%
|
1
5%
|
3
8.6%
|
6
5.4%
|
| ER and PR negative and HER2 positive |
0
0%
|
0
0%
|
1
2.9%
|
1
0.9%
|
| Sites at baseline (Count of Participants) | ||||
| <3 sites |
23
41.1%
|
7
35%
|
21
60%
|
51
45.9%
|
| ≥3 sites |
33
58.9%
|
13
65%
|
14
40%
|
60
54.1%
|
| Prior surgery (Count of Participants) | ||||
| Count of Participants [Participants] |
53
94.6%
|
19
95%
|
34
97.1%
|
106
95.5%
|
| Prior radiotherapy (Count of Participants) | ||||
| Count of Participants [Participants] |
44
78.6%
|
18
90%
|
32
91.4%
|
94
84.7%
|
| Weight (Kg) [Median (Full Range) ] | ||||
| Median (Full Range) [Kg] |
69.2
|
59.8
|
71.7
|
68.1
|
| Height (cm) [Median (Full Range) ] | ||||
| Median (Full Range) [cm] |
162.5
|
161.0
|
161.0
|
162.0
|
| Body Surface Area (m^2) [Median (Full Range) ] | ||||
| Median (Full Range) [m^2] |
1.72
|
1.63
|
1.75
|
1.72
|
| Albumin (g/dL) [Median (Full Range) ] | ||||
| Median (Full Range) [g/dL] |
4.1
|
4.1
|
4.0
|
4.1
|
| Number of sites at baseline (sites) [Median (Full Range) ] | ||||
| Median (Full Range) [sites] |
3.0
|
3.0
|
2.0
|
3.0
|
| Time from first diagnosis to registration (months) [Median (Full Range) ] | ||||
| Median (Full Range) [months] |
44.0
|
55.7
|
47.0
|
46.5
|
| Time from metastatic disease to registration (months) [Median (Full Range) ] | ||||
| Median (Full Range) [months] |
12.5
|
26.1
|
13.8
|
14.8
|
| Time from last progression before study entry (weeks) [Median (Full Range) ] | ||||
| Median (Full Range) [weeks] |
2.9
|
3.2
|
3.0
|
3.0
|
Outcome Measures
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Number (95% Confidence Interval) [percentage] |
40.7
|
5.0
|
8.8
|
| Title | Overall Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| CR |
2
3.6%
|
0
0%
|
0
0%
|
| PR |
20
35.7%
|
1
5%
|
3
8.6%
|
| SD |
24
42.9%
|
9
45%
|
17
48.6%
|
| PD |
8
14.3%
|
10
50%
|
13
37.1%
|
| TF |
0
0%
|
0
0%
|
1
2.9%
|
| Title | Duration of Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Responder patients (PR or CR, whichever was first reached) |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 22 | 1 | 3 |
| Median (95% Confidence Interval) [months] |
6.3
|
2.7
|
3.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort A (BRCA+), Cohort A1 (BRCA+/PARPi), Cohort B (Unselected) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0909 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Duration of Response Rate at 6 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Responder patients |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 22 | 1 | 3 |
| Number (95% Confidence Interval) [percentage of participants] |
53.1
94.8%
|
0
0%
|
33.3
95.1%
|
| Title | Duration of Response Rate at 12 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Responder patients |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 22 | 1 | 3 |
| Number (95% Confidence Interval) [percentage of participants] |
33.8
60.4%
|
0
0%
|
33.3
95.1%
|
| Title | Clinical Benefit Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
61.1
109.1%
|
40.0
200%
|
32.4
92.6%
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Median (95% Confidence Interval) [months] |
4.6
|
1.4
|
2.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort A (BRCA+), Cohort A1 (BRCA+/PARPi), Cohort B (Unselected) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Progression-free Survival at 3 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
63.5
113.4%
|
42.5
212.5%
|
35.5
101.4%
|
| Title | Progression-free Survival at 6 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
37.6
67.1%
|
21.3
106.5%
|
11.1
31.7%
|
| Title | Progression-free Survival at 12 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
20.5
36.6%
|
0
0%
|
3.7
10.6%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Median (95% Confidence Interval) [months] |
18.6
|
8.1
|
12.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort A (BRCA+), Cohort A1 (BRCA+/PARPi), Cohort B (Unselected) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0561 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Overall Survival Rate at 12 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
62.5
111.6%
|
29.7
148.5%
|
55.4
158.3%
|
| Title | Overall Survival Rate at 18 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cohort A: Two patients never treated; Cohort B: 1 patient due to lack of post-baseline tumor assessments |
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) |
|---|---|---|---|
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. |
| Measure Participants | 54 | 20 | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
53.4
95.4%
|
22.3
111.5%
|
27.7
79.1%
|
Adverse Events
| Time Frame | Participants were assessed through study completion, aproximately 6 years | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Two patients in Cohort A were never treated with lurbinectedin and therefore were not included in the analysis of safety | |||||
| Arm/Group Title | Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) | |||
| Arm/Group Description | Patients with known deleterious BRCA1/2 mutation status at study entry | Patients with known deleterious BRCA1/2 mutation status and prior treatment with PARPi. | 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. | |||
All Cause Mortality |
||||||
| Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 40/54 (74.1%) | 13/20 (65%) | 30/35 (85.7%) | |||
Serious Adverse Events |
||||||
| Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/54 (25.9%) | 5/20 (25%) | 8/35 (22.9%) | |||
| Blood and lymphatic system disorders | ||||||
| anaemia | 2/54 (3.7%) | 4 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Febrile neutropenia | 7/54 (13%) | 9 | 2/20 (10%) | 2 | 0/35 (0%) | 0 |
| Neutropenia | 2/54 (3.7%) | 2 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Thrombocytopenia | 6/54 (11.1%) | 9 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/54 (1.9%) | 2 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Cardiac failure congestive | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Pericardial effusion | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Nausea | 2/54 (3.7%) | 2 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Vomiting | 3/54 (5.6%) | 3 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| General disorders | ||||||
| Catheter site erythema | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Chest discomfort | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Drug interaction | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Hepatotoxicity | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Infections and infestations | ||||||
| Myelitis | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Pneumonia | 2/54 (3.7%) | 4 | 0/20 (0%) | 0 | 1/35 (2.9%) | 2 |
| Sepsis | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Urinary tract infection | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Staphylococcal bacteraemia | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Listeriosis | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Septic shock | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Medication error | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Fall | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Investigations | ||||||
| Neutropenia | 2/54 (3.7%) | 2 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Alanine aminotransferase increased | 2/54 (3.7%) | 2 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Aspartate aminotransferase increased | 2/54 (3.7%) | 2 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Platelet count decreased | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Failure to thrive | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Nervous system disorders | ||||||
| Syncope | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Pelvic pain | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 2/54 (3.7%) | 4 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Epistaxis | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Pneumonitis | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Pleural effusion | 0/54 (0%) | 0 | 1/20 (5%) | 2 | 0/35 (0%) | 0 |
| Respiratory failure | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Pulmonary embolism | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Vascular disorders | ||||||
| Hypotension | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Jugular vein thrombosis | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Cohort A (BRCA+) | Cohort A1 (BRCA+/PARPi) | Cohort B (Unselected) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 54/54 (100%) | 20/20 (100%) | 34/35 (97.1%) | |||
| Blood and lymphatic system disorders | ||||||
| anaemia | 13/54 (24.1%) | 16 | 2/20 (10%) | 3 | 6/35 (17.1%) | 10 |
| febrile neutropenia | 4/54 (7.4%) | 4 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| neutropenia | 24/54 (44.4%) | 48 | 11/20 (55%) | 15 | 7/35 (20%) | 9 |
| thrombocytopenia | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Cardiac disorders | ||||||
| tachycardia | 5/54 (9.3%) | 8 | 1/20 (5%) | 1 | 1/35 (2.9%) | 1 |
| Endocrine disorders | ||||||
| Cushingoid | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Eye disorders | ||||||
| diplopia | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| abdominal pain | 11/54 (20.4%) | 25 | 5/20 (25%) | 6 | 7/35 (20%) | 12 |
| constipation | 23/54 (42.6%) | 32 | 9/20 (45%) | 17 | 9/35 (25.7%) | 17 |
| diarrhoea | 16/54 (29.6%) | 23 | 4/20 (20%) | 7 | 5/35 (14.3%) | 6 |
| dyspepsia | 2/54 (3.7%) | 3 | 1/20 (5%) | 1 | 2/35 (5.7%) | 3 |
| nausea | 43/54 (79.6%) | 123 | 15/20 (75%) | 23 | 20/35 (57.1%) | 37 |
| odynophagia | 1/54 (1.9%) | 1 | 1/20 (5%) | 2 | 1/35 (2.9%) | 1 |
| vomiting | 23/54 (42.6%) | 48 | 7/20 (35%) | 9 | 10/35 (28.6%) | 13 |
| Gastrooesophageal reflux disease | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| General disorders | ||||||
| chills | 1/54 (1.9%) | 1 | 2/20 (10%) | 2 | 1/35 (2.9%) | 1 |
| fatigue | 48/54 (88.9%) | 195 | 10/20 (50%) | 21 | 30/35 (85.7%) | 66 |
| Gait disturbance | 1/54 (1.9%) | 3 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Influenza like illness | 3/54 (5.6%) | 4 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Infusion site pain | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Mucosal inflammation | 13/54 (24.1%) | 15 | 1/20 (5%) | 1 | 2/35 (5.7%) | 2 |
| Non-cardiac chest pain | 2/54 (3.7%) | 2 | 1/20 (5%) | 4 | 0/35 (0%) | 0 |
| Oedema | 5/54 (9.3%) | 13 | 2/20 (10%) | 2 | 4/35 (11.4%) | 5 |
| pain | 3/54 (5.6%) | 4 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Pyrexia | 8/54 (14.8%) | 10 | 4/20 (20%) | 5 | 6/35 (17.1%) | 16 |
| Chest discomfort | 0/54 (0%) | 0 | 2/20 (10%) | 3 | 0/35 (0%) | 0 |
| Localised oedema | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Hepatomegaly | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 3/35 (8.6%) | 3 |
| Infections and infestations | ||||||
| Bronchitis | 3/54 (5.6%) | 3 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Herpes zoster | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Nasopharyngitis | 4/54 (7.4%) | 5 | 1/20 (5%) | 2 | 1/35 (2.9%) | 1 |
| Pharyngitis | 3/54 (5.6%) | 3 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Sinusitis | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Upper respiratory tract infection | 2/54 (3.7%) | 2 | 1/20 (5%) | 1 | 2/35 (5.7%) | 2 |
| Urinary tract infection | 6/54 (11.1%) | 9 | 1/20 (5%) | 1 | 1/35 (2.9%) | 1 |
| Candidiasis | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Klebsiella infection | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Staphylococcal bacteraemia | 0/54 (0%) | 0 | 1/20 (5%) | 2 | 0/35 (0%) | 0 |
| Sputum purulent | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 2/35 (5.7%) | 5 |
| Injury, poisoning and procedural complications | ||||||
| Fall | 2/54 (3.7%) | 2 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Lower limb fracture | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Tooth fracture | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Investigations | ||||||
| Neutropenia | 24/54 (44.4%) | 48 | 11/20 (55%) | 15 | 7/35 (20%) | 9 |
| Alanine aminotransferase increased | 3/54 (5.6%) | 3 | 2/20 (10%) | 5 | 1/35 (2.9%) | 1 |
| Aspartate aminotransferase increased | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Breath sounds abnormal | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Gamma-glutamyltransferase increased | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 2/35 (5.7%) | 2 |
| Weight decreased | 0/54 (0%) | 0 | 2/20 (10%) | 2 | 2/35 (5.7%) | 2 |
| Platelet count decreased | 0/54 (0%) | 0 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 15/54 (27.8%) | 20 | 6/20 (30%) | 7 | 5/35 (14.3%) | 9 |
| Dehydration | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 1/35 (2.9%) | 1 |
| Hypokalaemia | 1/54 (1.9%) | 3 | 1/20 (5%) | 3 | 0/35 (0%) | 0 |
| Hypomagnesaemia | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 2/35 (5.7%) | 2 |
| Hyponatraemia | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 1/35 (2.9%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 4/54 (7.4%) | 6 | 4/20 (20%) | 6 | 3/35 (8.6%) | 3 |
| Back pain | 7/54 (13%) | 9 | 2/20 (10%) | 5 | 4/35 (11.4%) | 5 |
| Bone pain | 8/54 (14.8%) | 10 | 2/20 (10%) | 2 | 2/35 (5.7%) | 2 |
| Musculoskeletal discomfort | 3/54 (5.6%) | 3 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Musculoskeletal pain | 9/54 (16.7%) | 10 | 2/20 (10%) | 2 | 4/35 (11.4%) | 5 |
| Myalgia | 5/54 (9.3%) | 9 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Neck pain | 2/54 (3.7%) | 2 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Pain in extremity | 6/54 (11.1%) | 8 | 0/20 (0%) | 0 | 1/35 (2.9%) | 2 |
| Pain in jaw | 1/54 (1.9%) | 1 | 1/20 (5%) | 2 | 1/35 (2.9%) | 1 |
| Nervous system disorders | ||||||
| Dizziness | 7/54 (13%) | 9 | 2/20 (10%) | 3 | 3/35 (8.6%) | 4 |
| Dysgeusia | 3/54 (5.6%) | 8 | 2/20 (10%) | 2 | 0/35 (0%) | 0 |
| Headache | 16/54 (29.6%) | 29 | 6/20 (30%) | 10 | 5/35 (14.3%) | 5 |
| Neuralgia | 1/54 (1.9%) | 2 | 1/20 (5%) | 1 | 1/35 (2.9%) | 1 |
| Neuropathy peripheral | 6/54 (11.1%) | 6 | 1/20 (5%) | 1 | 2/35 (5.7%) | 2 |
| Tremor | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 8/54 (14.8%) | 9 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Depression | 3/54 (5.6%) | 3 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Insomnia | 4/54 (7.4%) | 4 | 2/20 (10%) | 2 | 1/35 (2.9%) | 1 |
| Renal and urinary disorders | ||||||
| Dysuria | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Pollakiuria | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Breast pain | 2/54 (3.7%) | 2 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Pelvic pain | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 16/54 (29.6%) | 21 | 2/20 (10%) | 2 | 6/35 (17.1%) | 9 |
| Dyspnoea | 11/54 (20.4%) | 12 | 5/20 (25%) | 11 | 8/35 (22.9%) | 12 |
| Nasal congestion | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Oropharyngeal pain | 1/54 (1.9%) | 1 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
| Pleural effusion | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Pulmonary embolism | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 1/35 (2.9%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 3/54 (5.6%) | 3 | 0/20 (0%) | 0 | 0/35 (0%) | 0 |
| Dry skin | 4/54 (7.4%) | 4 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Erythema | 3/54 (5.6%) | 3 | 0/20 (0%) | 0 | 1/35 (2.9%) | 1 |
| Pruritus | 1/54 (1.9%) | 1 | 0/20 (0%) | 0 | 2/35 (5.7%) | 2 |
| Rash | 8/54 (14.8%) | 10 | 1/20 (5%) | 1 | 2/35 (5.7%) | 2 |
| Skin hyperpigmentation | 2/54 (3.7%) | 2 | 1/20 (5%) | 1 | 1/35 (2.9%) | 1 |
| Vascular disorders | ||||||
| Deep vein thrombosis | 2/54 (3.7%) | 2 | 1/20 (5%) | 1 | 1/35 (2.9%) | 1 |
| Hot flush | 1/54 (1.9%) | 1 | 1/20 (5%) | 2 | 0/35 (0%) | 0 |
| Hypotension | 1/54 (1.9%) | 1 | 2/20 (10%) | 2 | 2/35 (5.7%) | 2 |
| Lymphoedema | 4/54 (7.4%) | 5 | 0/20 (0%) | 0 | 4/35 (11.4%) | 5 |
| Phlebitis | 4/54 (7.4%) | 5 | 2/20 (10%) | 3 | 2/35 (5.7%) | 2 |
| Flushing | 0/54 (0%) | 0 | 1/20 (5%) | 1 | 0/35 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review
Results Point of Contact
| Name/Title | Pharma Mar S.A. |
|---|---|
| Organization | Pharma Mar S.A. |
| Phone | 00 34 91846 60 00 |
| clinicaltrials@pharmamar.com |
- PM1183-B-003-11