A Study of MM-121 in Combination With Paclitaxel in Patients With Advanced Gynecologic and Breast Cancers
Sponsor
Merrimack Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01209195
Collaborator
Sanofi (Industry)
41
5
1
45
8.2
0.2
Study Details
Study Description
Brief Summary
This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial of MM-121 in combination with paclitaxel using a "3+3" design.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 1 dose was identified. Once the maximum tolerated dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints.
Study Design
Study Type:
Interventional
Actual Enrollment
:
41 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Paclitaxel in Patients With Advanced Gynecologic and Breast Cancers
Study Start Date
:
Oct 1, 2010
Actual Primary Completion Date
:
May 1, 2014
Actual Study Completion Date
:
Jul 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MM-121 + Paclitaxel Escalating doses of MM-121 given IV QW in combination with paclitaxel at standard dose of 80 mg/m2 IV QW |
Drug: MM-121
increasing doses of MM-121 IV QW
Other Names:
Drug: Paclitaxel
Paclitaxel - 80 mg/m2 IV QW
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Dose Escalation: To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Plus Paclitaxel Combination Via Reporting of Dose-limiting Toxicity (DLT) [From date of first dose to 30 days after termination, the longest 163 weeks]
To establish the safety of escalating doses of MM-121 in combination with paclitaxel in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: MM-121 Dose Level [From date of first dose to 30 days after termination, the longest 163 weeks]
Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: Paclitaxel Dose Level [From date of first dose to 30 days after termination, the longest 163 weeks]
Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest
Secondary Outcome Measures
- To Characterize the Efficacy of the Combination of MM-121 and Paclitaxel Using Objective Response Rate [patients were assessed for response during their time on study, the longest of which was 163 weeks]
To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response (PR) is defined as >20% decrease in tumor burden from baseline and a Complete Response (CR) is defined as complete disappearance from tumor burden from baseline. Objective Response is presented as the total # patients with PR or CR.
- To Determine the Pharmacokinetics (PK) of MM-121 When Administered in Combination With Paclitaxel [Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1]
Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (20/12 mg/kg weekly, 40/20 mg/kg weekly, 40 mg/kg Q2W, or 40/20 mg/kg QW x 7 plus a rest week).
- Pharmacokinetic Parameters (AUClast) [Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1]
Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (20/12 mg/kg weekly, 40/20 mg/kg weekly, 40 mg/kg Q2W, or 40/20 mg/kg QW x 7 plus a rest week). Immunogenicity data is not available.
- Immunogenicity [Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 163 weeks, and a collection was made post-infusion in any case of infusion reaction]
Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Cytological or histological confirmation of locally advanced/metastatic or recurrent epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer or endometrial cancer; OR, cytological or histological confirmation of locally advanced /metastatic Her2 non-overexpressing breast cancer
-
Eighteen years of age or above
-
Candidates for chemotherapy
-
Able to understand and sign an informed consent (or have a legal representative who is able to do so)
-
Measurable disease according to RECIST v1.1
-
ECOG Performance Score (PS) of ≤ 2
-
Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-121
Exclusion Criteria:
-
Prior radiation therapy to >25% of bone marrow-bearing areas
-
Evidence of any other active malignancy
-
Active infection or fever> 38.5°C during screening visits or on the first scheduled day of dosing
-
Symptomatic CNS disease
-
Known hypersensitivity to any of the components of MM-121 or who have had hypersensitivity reactions to fully human monoclonal antibodies
-
Received treatment, within 30 days prior to the first scheduled day of dosing, with any investigational agents that have not received regulatory approval for any indication or disease state
-
Pregnant or breast feeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham Comprehensive Cancer Center | Birmingham | Alabama | United States | 35294 |
| 2 | Pinnacle Oncology Hematology | Scottsdale | Arizona | United States | 85258 |
| 3 | Comprehensive Blood and Cancer Center | Bakersfield | California | United States | 93309 |
| 4 | Cancer Care Associates of Fresno | Fresno | California | United States | 93720 |
| 5 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
Sponsors and Collaborators
- Merrimack Pharmaceuticals
- Sanofi
Investigators
- Study Director: Akos Czibere, MD, PhD, Merrimack Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01209195
Other Study ID Numbers:
- MM-121-04-01-04
First Posted:
Sep 27, 2010
Last Update Posted:
Sep 8, 2016
Last Verified:
Sep 1, 2016
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Merrimack Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 | Part 1: Dose Escalation: Cohort 2 | Part 2: Expansion Cohort 1 | Part 2: Expansion Cohort 2 | Part 2: Cohort 3 | Part 2: Cohort 4 |
|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 - 20 mg/kg loading dose followed by 12 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 20 mg/kg IV loading dose followed by 12 mg/kg IV QW maintenance dose Paclitaxel: 80 mg/m2 weekly IV | MM-121 40mg/kg IV QOW Paclitaxel: 80 mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest Paclitaxel - 80mg/m2 weekly IV for 3 weeks, followed by one week of rest |
| Period Title: Overall Study | ||||||
| STARTED | 7 | 3 | 6 | 6 | 6 | 13 |
| COMPLETED | 7 | 3 | 6 | 6 | 6 | 13 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | MM-121 + Paclitaxel: Dose Escalation | MM-121 + Paclitaxel: Expansion Cohort | Total |
|---|---|---|---|
| Arm/Group Description | MM-121 plus Paclitaxel: Cohort 1: MM-121 - 20 mg/kg loading dose followed by 12 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV Cohort 2: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV Intermediate doses between cohorts 1 and 2 may also be considered. | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | Total of all reporting groups |
| Overall Participants | 10 | 31 | 41 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
57.4
(9.62)
|
55.5
(10.43)
|
56.45
(10.025)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
10
100%
|
31
100%
|
41
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
10%
|
10
32.3%
|
11
26.8%
|
| Not Hispanic or Latino |
9
90%
|
21
67.7%
|
30
73.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
3.2%
|
1
2.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
3
9.7%
|
3
7.3%
|
| White |
10
100%
|
22
71%
|
32
78%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
5
16.1%
|
5
12.2%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
10
100%
|
31
100%
|
41
100%
|
Outcome Measures
| Title | Dose Escalation: To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Plus Paclitaxel Combination Via Reporting of Dose-limiting Toxicity (DLT) |
|---|---|
| Description | To establish the safety of escalating doses of MM-121 in combination with paclitaxel in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD. |
| Time Frame | From date of first dose to 30 days after termination, the longest 163 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 | Part 1: Dose Escalation: Cohort 2 | Part 2: Expansion Cohort 1 | Part 2: Expansion Cohort 2 | Part 2: Cohort 3 | Part 2: Cohort 4 |
|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 - 20 mg/kg loading dose followed by 12 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 20 mg/kg IV loading dose followed by 12 mg/kg IV QW maintenance dose Paclitaxel: 80 mg/m2 weekly IV | MM-121 40mg/kg IV QOW Paclitaxel: 80 mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest Paclitaxel - 80mg/m2 weekly IV for 3 weeks, followed by one week of rest |
| Measure Participants | 7 | 3 | 6 | 6 | 6 | 13 |
| Number [participants reporting DLTs] |
0
0%
|
1
3.2%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: MM-121 Dose Level |
|---|---|
| Description | Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest |
| Time Frame | From date of first dose to 30 days after termination, the longest 163 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| NOTE: MTD of paclitaxel when administered with MM-121 provided in separate endpoint entry |
| Arm/Group Title | Part 1: Dose Escalation | Part 2: Expansion Cohorts |
|---|---|---|
| Arm/Group Description | Escalating doses of MM-121 and paclitaxel | Additional exploratory doses of MM-121 and paclitaxel |
| Measure Participants | 10 | 31 |
| one-time loading dose |
40
|
40
|
| maintenance dose |
20
|
20
|
| Title | To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Paclitaxel: Paclitaxel Dose Level |
|---|---|
| Description | Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest |
| Time Frame | From date of first dose to 30 days after termination, the longest 163 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| note: MTD of MM-121 when administered in combination with paclitaxel provided in separate endpoint entry |
| Arm/Group Title | Part 1: Dose Escalation | Part 2: Expansion Cohorts |
|---|---|---|
| Arm/Group Description | Escalating doses of MM-121 and paclitaxel | Additional exploratory doses of MM-121 and paclitaxel |
| Measure Participants | 10 | 31 |
| Number [mg/m2] |
80
|
80
|
| Title | To Characterize the Efficacy of the Combination of MM-121 and Paclitaxel Using Objective Response Rate |
|---|---|
| Description | To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response (PR) is defined as >20% decrease in tumor burden from baseline and a Complete Response (CR) is defined as complete disappearance from tumor burden from baseline. Objective Response is presented as the total # patients with PR or CR. |
| Time Frame | patients were assessed for response during their time on study, the longest of which was 163 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 | Part 1: Dose Escalation: Cohort 2 | Part 2: Expansion Cohort 1 | Part 2: Expansion Cohort 2 | Part 2: Cohort 3 | Part 2: Cohort 4 |
|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 - 20 mg/kg loading dose followed by 12 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 20 mg/kg IV loading dose followed by 12 mg/kg IV QW maintenance dose Paclitaxel: 80 mg/m2 weekly IV | MM-121 40mg/kg IV QOW Paclitaxel: 80 mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest Paclitaxel - 80mg/m2 weekly IV for 3 weeks, followed by one week of rest |
| Measure Participants | 7 | 3 | 6 | 6 | 6 | 13 |
| Number [participants with objective response] |
1
10%
|
2
6.5%
|
3
7.3%
|
3
NaN
|
3
NaN
|
2
NaN
|
| Title | To Determine the Pharmacokinetics (PK) of MM-121 When Administered in Combination With Paclitaxel |
|---|---|
| Description | Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (20/12 mg/kg weekly, 40/20 mg/kg weekly, 40 mg/kg Q2W, or 40/20 mg/kg QW x 7 plus a rest week). |
| Time Frame | Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients. Data presented per dose level of MM-121 and not per cohort. The same dose was used in multiple cohorts, and those data were combined. NOTE: two patients are not included in the analysis due to incorrectly collected or processed samples. |
| Arm/Group Title | MM-121 + Paclitaxel: 20/12 mg/kg | MM-121 + Paclitaxel: 40/20 mg/kg | MM-121 + Paclitaxel: 40 mg/kg Q2W | MM-121 + Paclitaxel: 40/20 mg/kg + Rest Week |
|---|---|---|---|---|
| Arm/Group Description | MM-121: 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Paclitaxel: 80 mg/m2 | MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Paclitaxel: 80 mg/m2 | MM-121: 40 mg/kg Q2W Paclitaxel: 80 mg/m2 | MM-121: 40 mg/kg loading dose followed by seven 20mg/kg weekly doses and a rest week. This administration schedule spans two cycles and repeats for each subsequent 2-cycle unit. Paclitaxel: 80 mg/m2 |
| Measure Participants | 12 | 9 | 6 | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [ug/mL] |
445.7
(39.6)
|
903.5
(31.5)
|
1081.1
(73.1)
|
1134.5
(18.6)
|
| Title | Pharmacokinetic Parameters (AUClast) |
|---|---|
| Description | Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (20/12 mg/kg weekly, 40/20 mg/kg weekly, 40 mg/kg Q2W, or 40/20 mg/kg QW x 7 plus a rest week). Immunogenicity data is not available. |
| Time Frame | Collections taken at for all patients at Cycle 1, Week 1 (pre-treatment/pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121) and pre-treatment at Cycle 1, Week 3 and Cycle 2, Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients. Data presented per dose level of MM-121 and not per cohort. The same dose was used in multiple cohorts, and those data were combined. NOTE: two patients are not included in the analysis due to incorrectly collected or processed samples. |
| Arm/Group Title | MM-121 + Paclitaxel: 20/12 mg/kg | MM-121 + Paclitaxel: 40/20 mg/kg | MM-121 + Paclitaxel: 40 mg/kg Q2W | MM-121 + Paclitaxel: 40/20 mg/kg + Rest Week |
|---|---|---|---|---|
| Arm/Group Description | MM-121: 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Paclitaxel: 80 mg/m2 | MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Paclitaxel: 80 mg/m2 | MM-121: 40 mg/kg Q2W Paclitaxel: 80 mg/m2 | MM-121: 40 mg/kg loading dose followed by seven 20mg/kg weekly doses and a rest week. This administration schedule spans two cycles and repeats for each subsequent 2-cycle unit. Paclitaxel: 80 mg/m2 |
| Measure Participants | 12 | 9 | 6 | 12 |
| Geometric Mean (Geometric Coefficient of Variation) [hr* ug/mL] |
39252.9
(40.3)
|
77137.6
(31.1)
|
102263.1
(35.6)
|
96043.0
(25.9)
|
| Title | Immunogenicity |
|---|---|
| Description | Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies). |
| Time Frame | Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 163 weeks, and a collection was made post-infusion in any case of infusion reaction |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 | Part 1: Dose Escalation: Cohort 2 | Part 2: Expansion Cohort 1 | Part 2: Expansion Cohort 2 | Part 2: Cohort 3 | Part 2: Cohort 4 |
|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 - 20 mg/kg loading dose followed by 12 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | MM-121 20 mg/kg IV loading dose followed by 12 mg/kg IV QW maintenance dose Paclitaxel: 80 mg/m2 weekly IV | MM-121 40mg/kg IV QOW Paclitaxel: 80 mg/m2 weekly IV | MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest Paclitaxel - 80mg/m2 weekly IV for 3 weeks, followed by one week of rest |
| Measure Participants | 7 | 3 | 6 | 6 | 6 | 13 |
| Number |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
Adverse Events
| Time Frame | AEs were collected from a patient's first dose until 30 days after treatment termination. SAEs were collected from time of informed consent until 30 days after termination. If related, events could be reported at any time after termination. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for ~1 year after termination | |||
| Arm/Group Title | MM-121 + Paclitaxel: Dose Escalation | MM-121 + Paclitaxel: Expansion Cohort | ||
| Arm/Group Description | Cohort 1: MM-121 - 20 mg/kg loading dose followed by 12 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV Cohort 2: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV | Cohort 1: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV Paclitaxel - 80mg/m2 weekly IV Cohort 2: MM-121 20 mg/kg IV loading dose x followed by 12 mg/kg IV QW maintenance dose Paclitaxel: 80 mg/m2 weekly IV Cohort 3: MM-121 40mg/kg IV QOW Paclitaxel: 80 mg/m2 weekly IV Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest Paclitaxel - 80mg/m2 weekly IV for 3 weeks, followed by one week of rest | ||
All Cause Mortality |
||||
| MM-121 + Paclitaxel: Dose Escalation | MM-121 + Paclitaxel: Expansion Cohort | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| MM-121 + Paclitaxel: Dose Escalation | MM-121 + Paclitaxel: Expansion Cohort | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/10 (40%) | 12/31 (38.7%) | ||
| Gastrointestinal disorders | ||||
| SMALL INTESTINAL OBSTRUCTION | 3/10 (30%) | 0/31 (0%) | ||
| INTESTINAL OBSTRUCTION | 1/10 (10%) | 0/31 (0%) | ||
| INTESTINAL PERFORATION | 1/10 (10%) | 0/31 (0%) | ||
| ABDOMINAL PAIN | 0/10 (0%) | 1/31 (3.2%) | ||
| DIARRHOEA | 0/10 (0%) | 1/31 (3.2%) | ||
| GASTRITIS | 0/10 (0%) | 1/31 (3.2%) | ||
| PEPTIC ULCER | 0/10 (0%) | 1/31 (3.2%) | ||
| General disorders | ||||
| DEATH | 1/10 (10%) | 0/31 (0%) | ||
| DISEASE PROGRESSION | 0/10 (0%) | 3/31 (9.7%) | ||
| FATIGUE | 0/10 (0%) | 2/31 (6.5%) | ||
| Infections and infestations | ||||
| SEPSIS | 0/10 (0%) | 1/31 (3.2%) | ||
| Injury, poisoning and procedural complications | ||||
| ACCIDENTAL OVERDOSE | 0/10 (0%) | 2/31 (6.5%) | ||
| HEPATIC HAEMATOMA | 0/10 (0%) | 1/31 (3.2%) | ||
| OVERDOSE | 0/10 (0%) | 1/31 (3.2%) | ||
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 1/10 (10%) | 0/31 (0%) | ||
| HYPONATRAEMIA | 1/10 (10%) | 0/31 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| MALIGNANT PLEURAL EFFUSION | 0/10 (0%) | 1/31 (3.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| PULMONARY EMBOLISM | 1/10 (10%) | 0/31 (0%) | ||
| DYSPNOEA | 0/10 (0%) | 2/31 (6.5%) | ||
| PLEURAL EFFUSION | 0/10 (0%) | 2/31 (6.5%) | ||
| PNEUMONITIS | 0/10 (0%) | 1/31 (3.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| ONYCHOMADESIS | 1/10 (10%) | 0/31 (0%) | ||
| Vascular disorders | ||||
| THROMBOSIS | 0/10 (0%) | 1/31 (3.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| MM-121 + Paclitaxel: Dose Escalation | MM-121 + Paclitaxel: Expansion Cohort | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 31/31 (100%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 5/10 (50%) | 9/31 (29%) | ||
| NEUTROPENIA | 5/10 (50%) | 12/31 (38.7%) | ||
| LEUKOPENIA | 0/10 (0%) | 3/31 (9.7%) | ||
| PANCYTOPENIA | 0/10 (0%) | 3/31 (9.7%) | ||
| LYMPHOPENIA | 0/10 (0%) | 2/31 (6.5%) | ||
| THROMBOCYTOPENIA | 0/10 (0%) | 2/31 (6.5%) | ||
| Ear and labyrinth disorders | ||||
| EAR DISORDER | 1/10 (10%) | 0/31 (0%) | ||
| VERTIGO | 1/10 (10%) | 0/31 (0%) | ||
| CONJUNCTIVAL IRRITATION | 1/10 (10%) | 0/31 (0%) | ||
| EYE PRURITUS | 1/10 (10%) | 0/31 (0%) | ||
| OCULAR HYPERAEMIA | 1/10 (10%) | 0/31 (0%) | ||
| Eye disorders | ||||
| LACRIMATION INCREASED | 0/10 (0%) | 3/31 (9.7%) | ||
| CONJUNCTIVITIS | 0/10 (0%) | 2/31 (6.5%) | ||
| VISION BLURRED | 1/10 (10%) | 2/31 (6.5%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 9/10 (90%) | 7/31 (22.6%) | ||
| DIARRHOEA | 5/10 (50%) | 18/31 (58.1%) | ||
| STOMATITIS | 5/10 (50%) | 9/31 (29%) | ||
| NAUSEA | 4/10 (40%) | 13/31 (41.9%) | ||
| SMALL INTESTINAL OBSTRUCTION | 3/10 (30%) | 0/31 (0%) | ||
| CONSTIPATION | 2/10 (20%) | 8/31 (25.8%) | ||
| GASTROOESOPHAGEAL REFLUX DISEASE | 2/10 (20%) | 3/31 (9.7%) | ||
| VOMITING | 2/10 (20%) | 8/31 (25.8%) | ||
| ABDOMINAL DISTENSION | 1/10 (10%) | 4/31 (12.9%) | ||
| DRY MOUTH | 1/10 (10%) | 2/31 (6.5%) | ||
| DYSPEPSIA | 1/10 (10%) | 5/31 (16.1%) | ||
| FLATULENCE | 1/10 (10%) | 2/31 (6.5%) | ||
| GASTRITIS | 1/10 (10%) | 1/31 (3.2%) | ||
| GASTROINTESTINAL PAIN | 1/10 (10%) | 0/31 (0%) | ||
| GINGIVAL BLEEDING | 1/10 (10%) | 0/31 (0%) | ||
| INTESTINAL OBSTRUCTION | 1/10 (10%) | 0/31 (0%) | ||
| MELAENA | 0/10 (0%) | 2/31 (6.5%) | ||
| ORAL DISORDER | 0/10 (0%) | 2/31 (6.5%) | ||
| ORAL PAIN | 0/10 (0%) | 2/31 (6.5%) | ||
| ASCITES | 0/10 (0%) | 2/31 (6.5%) | ||
| ABDOMINAL PAIN UPPER | 0/10 (0%) | 3/31 (9.7%) | ||
| INTESTINAL PERFORATION | 1/10 (10%) | 0/31 (0%) | ||
| HAEMORRHOIDS | 0/10 (0%) | 6/31 (19.4%) | ||
| General disorders | ||||
| FATIGUE | 7/10 (70%) | 22/31 (71%) | ||
| CHEST DISCOMFORT | 2/10 (20%) | 1/31 (3.2%) | ||
| CHILLS | 2/10 (20%) | 1/31 (3.2%) | ||
| MUCOSAL INFLAMMATION | 2/10 (20%) | 5/31 (16.1%) | ||
| OEDEMA PERIPHERAL | 2/10 (20%) | 12/31 (38.7%) | ||
| PAIN | 2/10 (20%) | 2/31 (6.5%) | ||
| CATHETER SITE PAIN | 1/10 (10%) | 0/31 (0%) | ||
| DEATH | 1/10 (10%) | 0/31 (0%) | ||
| DISEASE PROGRESSION | 1/10 (10%) | 0/31 (0%) | ||
| EARLY SATIETY | 1/10 (10%) | 0/31 (0%) | ||
| FACIAL PAIN | 1/10 (10%) | 0/31 (0%) | ||
| OEDEMA | 1/10 (10%) | 0/31 (0%) | ||
| PYREXIA | 1/10 (10%) | 4/31 (12.9%) | ||
| ASTHENIA | 0/10 (0%) | 2/31 (6.5%) | ||
| CHEST PAIN | 0/10 (0%) | 2/31 (6.5%) | ||
| FACE OEDEMA | 0/10 (0%) | 2/31 (6.5%) | ||
| Infections and infestations | ||||
| URINARY TRACT INFECTION | 3/10 (30%) | 7/31 (22.6%) | ||
| HORDEOLUM | 2/10 (20%) | 0/31 (0%) | ||
| SINUSITIS | 2/10 (20%) | 1/31 (3.2%) | ||
| FUNGAL INFECTION | 1/10 (10%) | 1/31 (3.2%) | ||
| HERPES ZOSTER | 1/10 (10%) | 0/31 (0%) | ||
| NAIL INFECTION | 1/10 (10%) | 0/31 (0%) | ||
| ONYCHOMYCOSIS | 1/10 (10%) | 0/31 (0%) | ||
| PARONYCHIA | 1/10 (10%) | 1/31 (3.2%) | ||
| PNEUMONIA | 1/10 (10%) | 2/31 (6.5%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 1/10 (10%) | 8/31 (25.8%) | ||
| URINARY TRACT INFECTION PSEUDOMONAL | 1/10 (10%) | 0/31 (0%) | ||
| VAGINAL INFECTION | 1/10 (10%) | 0/31 (0%) | ||
| CELLULITIS | 0/10 (0%) | 2/31 (6.5%) | ||
| INFECTION | 0/10 (0%) | 2/31 (6.5%) | ||
| Injury, poisoning and procedural complications | ||||
| PROCEDURAL PAIN | 2/10 (20%) | 1/31 (3.2%) | ||
| ARTHROPOD BITE | 1/10 (10%) | 1/31 (3.2%) | ||
| FALL | 1/10 (10%) | 0/31 (0%) | ||
| RIB FRACTURE | 1/10 (10%) | 0/31 (0%) | ||
| ACCIDENTAL OVERDOSE | 0/10 (0%) | 2/31 (6.5%) | ||
| Investigations | ||||
| BACTERIAL TEST | 1/10 (10%) | 1/31 (3.2%) | ||
| BLOOD CREATININE INCREASED | 1/10 (10%) | 1/31 (3.2%) | ||
| HAEMATOCRIT DECREASED | 1/10 (10%) | 0/31 (0%) | ||
| HEART RATE INCREASED | 1/10 (10%) | 0/31 (0%) | ||
| SKIN TURGOR DECREASED | 1/10 (10%) | 0/31 (0%) | ||
| WHITE BLOOD CELL COUNT DECREASED | 1/10 (10%) | 1/31 (3.2%) | ||
| WHITE BLOOD CELL COUNT INCREASED | 1/10 (10%) | 0/31 (0%) | ||
| ASPARTATE AMINOTRANSFERASE INCREASED | 0/10 (0%) | 5/31 (16.1%) | ||
| BLOOD LACTATE DEHYDROGENASE INCREASED | 0/10 (0%) | 4/31 (12.9%) | ||
| ALANINE AMINOTRANSFERASE INCREASED | 0/10 (0%) | 3/31 (9.7%) | ||
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | 0/10 (0%) | 3/31 (9.7%) | ||
| WEIGHT DECREASED | 0/10 (0%) | 3/31 (9.7%) | ||
| Metabolism and nutrition disorders | ||||
| HYPOKALAEMIA | 3/10 (30%) | 9/31 (29%) | ||
| HYPOMAGNESAEMIA | 3/10 (30%) | 5/31 (16.1%) | ||
| DECREASED APPETITE | 2/10 (20%) | 6/31 (19.4%) | ||
| DEHYDRATION | 2/10 (20%) | 5/31 (16.1%) | ||
| HYPOCALCAEMIA | 1/10 (10%) | 3/31 (9.7%) | ||
| HYPONATRAEMIA | 1/10 (10%) | 5/31 (16.1%) | ||
| HYPOPHOSPHATAEMIA | 1/10 (10%) | 2/31 (6.5%) | ||
| HYPERGLYCEMIA | 0/10 (0%) | 2/31 (6.5%) | ||
| HYPOALBUMINAEMIA | 0/10 (0%) | 2/31 (6.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRALGIA | 2/10 (20%) | 4/31 (12.9%) | ||
| BACK PAIN | 2/10 (20%) | 7/31 (22.6%) | ||
| GROIN PAIN | 2/10 (20%) | 0/31 (0%) | ||
| PAIN IN EXTREMITY | 2/10 (20%) | 3/31 (9.7%) | ||
| MUSCLE SPASMS | 1/10 (10%) | 4/31 (12.9%) | ||
| MUSCULOSKELETAL CHEST PAIN | 1/10 (10%) | 0/31 (0%) | ||
| MYALGIA | 1/10 (10%) | 3/31 (9.7%) | ||
| NECK PAIN | 1/10 (10%) | 0/31 (0%) | ||
| PAIN IN JAW | 1/10 (10%) | 0/31 (0%) | ||
| BONE PAIN | 0/10 (0%) | 3/31 (9.7%) | ||
| Nervous system disorders | ||||
| NEUROPATHY PERIPHERAL | 4/10 (40%) | 22/31 (71%) | ||
| DYSGEUSIA | 3/10 (30%) | 2/31 (6.5%) | ||
| DIZZINESS | 2/10 (20%) | 6/31 (19.4%) | ||
| HEMICEPHALALGIA | 1/10 (10%) | 0/31 (0%) | ||
| VISUAL FIELD DEFECT | 1/10 (10%) | 0/31 (0%) | ||
| HEADACHE | 0/10 (0%) | 5/31 (16.1%) | ||
| PERIPHERAL SENSORY NEUROPATHY | 0/10 (0%) | 4/31 (12.9%) | ||
| DYSARTHRIA | 0/10 (0%) | 3/31 (9.7%) | ||
| HYPOAESTHESIA | 0/10 (0%) | 2/31 (6.5%) | ||
| SCIATICA | 0/10 (0%) | 2/31 (6.5%) | ||
| Psychiatric disorders | ||||
| ANXIETY | 2/10 (20%) | 2/31 (6.5%) | ||
| DEPRESSION | 2/10 (20%) | 2/31 (6.5%) | ||
| INSOMNIA | 2/10 (20%) | 5/31 (16.1%) | ||
| Renal and urinary disorders | ||||
| DYSURIA | 2/10 (20%) | 5/31 (16.1%) | ||
| NOCTURIA | 2/10 (20%) | 1/31 (3.2%) | ||
| POLLAKIURIA | 1/10 (10%) | 0/31 (0%) | ||
| URETHRITIS NONINFECTIVE | 1/10 (10%) | 0/31 (0%) | ||
| URINARY TRACT PAIN | 1/10 (10%) | 0/31 (0%) | ||
| Reproductive system and breast disorders | ||||
| VAGINAL DISCHARGE | 1/10 (10%) | 0/31 (0%) | ||
| VAGINAL HAEMORRHAGE | 1/10 (10%) | 0/31 (0%) | ||
| VULVOVAGINAL DISCOMFORT | 1/10 (10%) | 0/31 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| EPISTAXIS | 5/10 (50%) | 10/31 (32.3%) | ||
| COUGH | 2/10 (20%) | 6/31 (19.4%) | ||
| DYSPNOEA | 2/10 (20%) | 8/31 (25.8%) | ||
| DYSPHONIA | 1/10 (10%) | 1/31 (3.2%) | ||
| NASAL CONGESTION | 1/10 (10%) | 1/31 (3.2%) | ||
| NASAL DRYNESS | 1/10 (10%) | 0/31 (0%) | ||
| OROPHARYNGEAL PAIN | 1/10 (10%) | 5/31 (16.1%) | ||
| PULMONARY EMBOLISM | 1/10 (10%) | 0/31 (0%) | ||
| RHINORROEA | 0/10 (0%) | 4/31 (12.9%) | ||
| SINUS CONGESTION | 0/10 (0%) | 3/31 (9.7%) | ||
| PLEURAL EFFUSION | 0/10 (0%) | 2/31 (6.5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| RASH | 6/10 (60%) | 11/31 (35.5%) | ||
| ALOPECIA | 3/10 (30%) | 15/31 (48.4%) | ||
| PRURITUS | 3/10 (30%) | 6/31 (19.4%) | ||
| NAIL DISORDER | 2/10 (20%) | 7/31 (22.6%) | ||
| SKIN HYPERPIGMENTATION | 2/10 (20%) | 0/31 (0%) | ||
| DERMATITIS ACNEIFORM | 1/10 (10%) | 0/31 (0%) | ||
| DRY SKIN | 1/10 (10%) | 1/31 (3.2%) | ||
| ERYTHEMA | 1/10 (10%) | 0/31 (0%) | ||
| HYPERHIDROSIS | 1/10 (10%) | 0/31 (0%) | ||
| HYPERKERATOSIS | 1/10 (10%) | 0/31 (0%) | ||
| NAIL DISCOLOURATION | 1/10 (10%) | 0/31 (0%) | ||
| ONYCHALGIA | 1/10 (10%) | 1/31 (3.2%) | ||
| ONYCHOMADESIS | 1/10 (10%) | 1/31 (3.2%) | ||
| PAIN OF SKIN | 1/10 (10%) | 0/31 (0%) | ||
| PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME | 1/10 (10%) | 0/31 (0%) | ||
| PETECHIAE | 1/10 (10%) | 0/31 (0%) | ||
| RASH MACULAR | 1/10 (10%) | 0/31 (0%) | ||
| RASH MACULO-PAPULAR | 1/10 (10%) | 1/31 (3.2%) | ||
| SKIN ULCER | 1/10 (10%) | 1/31 (3.2%) | ||
| RASH PRURITIC | 0/10 (0%) | 3/31 (9.7%) | ||
| INGROWING NAIL | 0/10 (0%) | 2/31 (6.5%) | ||
| NIGHT SWEATS | 0/10 (0%) | 2/31 (6.5%) | ||
| Vascular disorders | ||||
| HOT FLUSH | 1/10 (10%) | 2/31 (6.5%) | ||
Limitations/Caveats
[Not Specified]
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. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Clinical Trial Manager |
|---|---|
| Organization | Merrimack Pharmaceuticals, Inc. |
| Phone | 617-441-1000 |
| smathews@merrimack.com |
Responsible Party:
Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01209195
Other Study ID Numbers:
- MM-121-04-01-04
First Posted:
Sep 27, 2010
Last Update Posted:
Sep 8, 2016
Last Verified:
Sep 1, 2016