Metastatic Breast Cancer
Conditions
Keywords
Herceptin, metastatic breast cancer, CT-P6, Her 2-positive
Brief summary
The purpose of the study is to demonstrate equivalence
Detailed description
Patients will receive CT-P6 or Herceptin every 3 weeks.
Interventions
DRUGCT-P6
Administered every 3 weeks
DRUGHerceptin
Administered every 3 weeks
DRUGPaclitaxel
Administered every 3 weeks
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are females * Have Her 2 over-expression * Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Exclusion criteria
* Current clinical or radiographic evidence central nervous system (CNS) metastases * Current Known infection * Pregnant or nursing mother
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 6 months (up to 24 weeks) | Best Overall Response (BOR) was derived from the overall response across all time points until after Cycle 8 using Independent Tumor Review Committee (ITRC) data in the FAS. Objective Response Rate (ORR) was defined as the number of patients with a BOR of complete response (CR) or partial response (PR) divided by the number of patients in the corresponding population, as assessed by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | Through study completion, approximately 40 months | Time from randomization to observed tumor response (Complete Response or Partial Response), as assessed by RECIST 1.1 |
| Progression Free Survival | Through study completion, approximately 40 months | Time from randomization to radiological progression or death from any cause, as assessed by RECIST 1.1 |
| Overall Survival | Through study completion, approximately 40 months | The number of days between the date of randomization and the date of death from any cause. |
| Time to Progression | Through study completion, approximately 40 months | Time from randomization to determined progressive disease, as assessed by RECIST version 1.1. |
| Safety Endpoints; Immunogenicity | During treatment, median of 13 cycles (every cycle is 3 weeks) | Assessed by the proportion of patients with development of antibodies to study drug (positive anti-drug antibody \[ADA\] results after the first study drug infusion) |
| Pharmacokinetic Endpoints; Ctroughss | predose and at 1.5 hours (end of infusion) of each cycle | Trough concentration at steady state |
| Safety Endpoints; Cardiotoxicity | Through study completion, approximately 40 months | Mean change from baseline to endpoint assessment in left ventricular ejection fraction (LVEF) (%) |
Countries
South Korea
Participant flow
Pre-assignment details
A total of 475 patients initiated Main Study Treatment Period and were included in the Full Analysis Set (FAS).
Participants by arm
| Arm | Count |
|---|---|
| CT-P6 CT-P6: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks.
Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (CT-P6). Paclitaxel cycles were repeated every 3 weeks. | 244 |
| Herceptin Herceptin: 8 mg/kg for loading or 6 mg/kg for maintenance dose via IV infusion every 3 weeks.
Paclitaxel: 175 mg/m2 BSA via IV infusion on the day following the first dose of study drug (Herceptin). Paclitaxel cycles were repeated every 3 weeks. | 231 |
| Total | 475 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Main Study Treatment Period | Adverse Event | 12 | 7 |
| Main Study Treatment Period | Disease Progression | 41 | 24 |
| Main Study Treatment Period | Other | 0 | 1 |
| Main Study Treatment Period | Other Reason | 0 | 1 |
| Main Study Treatment Period | Physician Decision | 2 | 0 |
| Main Study Treatment Period | Withdrawal by Subject | 4 | 6 |
| Treatment Period Beyond Cycle 8 | Adverse Event | 8 | 2 |
| Treatment Period Beyond Cycle 8 | Disease Progression | 129 | 119 |
| Treatment Period Beyond Cycle 8 | Other | 6 | 9 |
| Treatment Period Beyond Cycle 8 | Other Reason | 7 | 13 |
| Treatment Period Beyond Cycle 8 | Physician Decision | 6 | 5 |
| Treatment Period Beyond Cycle 8 | Withdrawal by Subject | 12 | 20 |
Baseline characteristics
| Characteristic | CT-P6 | Total | Herceptin |
|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 9.7 | 52.9 years STANDARD_DEVIATION 10.26 | 51.9 years STANDARD_DEVIATION 10.75 |
| Age, Customized <65 years | 210 Participants | 419 Participants | 209 Participants |
| Age, Customized >=65 years | 34 Participants | 56 Participants | 22 Participants |
| BSA at Screening | 1.72 m2 STANDARD_DEVIATION 0.203 | 1.73 m2 STANDARD_DEVIATION 0.212 | 1.74 m2 STANDARD_DEVIATION 0.22 |
| Childbearing Potential No | 191 Participants | 348 Participants | 157 Participants |
| Childbearing Potential Yes | 53 Participants | 127 Participants | 74 Participants |
| ECOG performance status Grade 0 | 128 Participants | 244 Participants | 116 Participants |
| ECOG performance status Grade 1 | 115 Participants | 230 Participants | 115 Participants |
| ECOG performance status Grade 2 | 1 Participants | 1 Participants | 0 Participants |
| Height at Screening | 159.5 cm STANDARD_DEVIATION 6.98 | 159.2 cm STANDARD_DEVIATION 7.09 | 158.9 cm STANDARD_DEVIATION 7.21 |
| Karnofsky performance status Category 1 | 236 Participants | 453 Participants | 217 Participants |
| Karnofsky performance status Category 2 | 4 Participants | 11 Participants | 7 Participants |
| Karnofsky performance status Not reported | 4 Participants | 11 Participants | 7 Participants |
| Prior Chemotherapy No | 137 Participants | 268 Participants | 131 Participants |
| Prior Chemotherapy Yes | 107 Participants | 207 Participants | 100 Participants |
| Race/Ethnicity, Customized Asian | 86 Participants | 176 Participants | 90 Participants |
| Race/Ethnicity, Customized White | 158 Participants | 299 Participants | 141 Participants |
| Region of Enrollment Belarus | 8 Participants | 16 Participants | 8 Participants |
| Region of Enrollment Bulgaria | 13 Participants | 20 Participants | 7 Participants |
| Region of Enrollment Georgia | 10 Participants | 21 Participants | 11 Participants |
| Region of Enrollment Hong Kong | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment India | 31 Participants | 66 Participants | 35 Participants |
| Region of Enrollment Latvia | 7 Participants | 13 Participants | 6 Participants |
| Region of Enrollment Malaysia | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Philippines | 17 Participants | 32 Participants | 15 Participants |
| Region of Enrollment Poland | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment Romania | 6 Participants | 13 Participants | 7 Participants |
| Region of Enrollment Russia | 47 Participants | 86 Participants | 39 Participants |
| Region of Enrollment Serbia | 4 Participants | 9 Participants | 5 Participants |
| Region of Enrollment Singapore | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment South Korea | 31 Participants | 63 Participants | 32 Participants |
| Region of Enrollment Thailand | 4 Participants | 7 Participants | 3 Participants |
| Region of Enrollment Turkey | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment Ukraine | 55 Participants | 107 Participants | 52 Participants |
| Sex: Female, Male Female | 244 Participants | 475 Participants | 231 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight at Screening | 67.5 kg STANDARD_DEVIATION 14.85 | 68.4 kg STANDARD_DEVIATION 15.46 | 69.3 kg STANDARD_DEVIATION 16.06 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 244 | 8 / 231 |
| other Total, other adverse events | 227 / 244 | 214 / 231 |
| serious Total, serious adverse events | 34 / 244 | 39 / 231 |
Outcome results
Primary
Objective Response Rate
Best Overall Response (BOR) was derived from the overall response across all time points until after Cycle 8 using Independent Tumor Review Committee (ITRC) data in the FAS. Objective Response Rate (ORR) was defined as the number of patients with a BOR of complete response (CR) or partial response (PR) divided by the number of patients in the corresponding population, as assessed by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.
Time frame: 6 months (up to 24 weeks)
Population: Full Analysis Set - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CT-P6 | Objective Response Rate | 138 Participants |
| Herceptin | Objective Response Rate | 143 Participants |
95% CI: [-0.143, 0.036]
Secondary
Overall Survival
The number of days between the date of randomization and the date of death from any cause.
Time frame: Through study completion, approximately 40 months
Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P6 | Overall Survival | 28.82 months |
| Herceptin | Overall Survival | 26.84 months |
Secondary
Pharmacokinetic Endpoints; Ctroughss
Trough concentration at steady state
Time frame: predose and at 1.5 hours (end of infusion) of each cycle
Population: PK Analysis Set (PKAS) - consisted of all FAS patients who had achieved steady state by the 8th cycle, which required 3 consecutive similar trough concentrations.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P6 | Pharmacokinetic Endpoints; Ctroughss | 23.6 ug/mL | Standard Deviation 24.5 |
| Herceptin | Pharmacokinetic Endpoints; Ctroughss | 24.2 ug/mL | Standard Deviation 27.8 |
Secondary
Progression Free Survival
Time from randomization to radiological progression or death from any cause, as assessed by RECIST 1.1
Time frame: Through study completion, approximately 40 months
Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CT-P6 | Progression Free Survival | 10.99 months |
| Herceptin | Progression Free Survival | 11.15 months |
Secondary
Safety Endpoints; Cardiotoxicity
Mean change from baseline to endpoint assessment in left ventricular ejection fraction (LVEF) (%)
Time frame: Through study completion, approximately 40 months
Population: Safety Analysis Set (SAF) - consisted of all patients in the FAS, analyzed as treated. All patients who received at least one dose of CT-P6 were analyzed under the CT-P6 treatment group. All other patients were analyzed under the Herceptin treatment group.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CT-P6 | Safety Endpoints; Cardiotoxicity | -4.56 %; percent change in LVEF | Standard Deviation 6.56 |
| Herceptin | Safety Endpoints; Cardiotoxicity | -4.98 %; percent change in LVEF | Standard Deviation 6.54 |
Secondary
Safety Endpoints; Immunogenicity
Assessed by the proportion of patients with development of antibodies to study drug (positive anti-drug antibody \[ADA\] results after the first study drug infusion)
Time frame: During treatment, median of 13 cycles (every cycle is 3 weeks)
Population: Safety Analysis Set (SAF) - consisted of all patients in the FAS, analyzed as treated. All patients who received at least one dose of CT-P6 were analyzed under the CT-P6 treatment group. All other patients were analyzed under the Herceptin treatment group.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT-P6 | Safety Endpoints; Immunogenicity | ADA positive patients with at least 1 result at any time during the study | 4 Participants |
| CT-P6 | Safety Endpoints; Immunogenicity | ADA positive patients with a result at baseline visit | 1 Participants |
| CT-P6 | Safety Endpoints; Immunogenicity | ADA positive patients with at least 1 result after the first infusion | 3 Participants |
| Herceptin | Safety Endpoints; Immunogenicity | ADA positive patients with at least 1 result at any time during the study | 2 Participants |
| Herceptin | Safety Endpoints; Immunogenicity | ADA positive patients with a result at baseline visit | 2 Participants |
| Herceptin | Safety Endpoints; Immunogenicity | ADA positive patients with at least 1 result after the first infusion | 0 Participants |
Secondary
Time to Progression
Time from randomization to determined progressive disease, as assessed by RECIST version 1.1.
Time frame: Through study completion, approximately 40 months
Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CT-P6 | Time to Progression | ITRC | 11.07 months |
| CT-P6 | Time to Progression | Investigator | 10.99 months |
| Herceptin | Time to Progression | ITRC | 12.52 months |
| Herceptin | Time to Progression | Investigator | 11.25 months |
Secondary
Time to Response
Time from randomization to observed tumor response (Complete Response or Partial Response), as assessed by RECIST 1.1
Time frame: Through study completion, approximately 40 months
Population: Full Analysis Set (FAS) - consisted of all randomized patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication.~All outcome measures of the Phase 3 study (CT-P6 3.1) were analyzed in conjunction with those of the Phase 1/2b study (CT-P6 1.1).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CT-P6 | Time to Response | ITRC | 1.38 months |
| CT-P6 | Time to Response | Investigator | 1.41 months |
| Herceptin | Time to Response | ITRC | 1.38 months |
| Herceptin | Time to Response | Investigator | 1.41 months |