Safety Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors
Sponsor
Merrimack Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01447225
Collaborator
Sanofi (Industry)
43
5
4
27
8.6
0.3
Study Details
Study Description
Brief Summary
To evaluate the safety and tolerability of escalating doses of MM-121 + certain anticancer therapies
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This study was a Phase 1 and pharmacologic dose-escalation trial of MM-121 in combination with certain anticancer therapies. The dose-escalation portion of the study employed a 3 + 3 design to assess the safety, tolerability, and pharmacokinetics of MM-121 administered weekly in combination with certain anticancer therapies in patients with advanced/recurrent cancer. Doses of MM-121 and/or the anticancer therapy were escalated until either the MTD is identified or the combination was shown to be tolerable at the highest planned doses.
Study Design
Study Type:
Interventional
Actual Enrollment
:
43 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors
Study Start Date
:
Oct 1, 2011
Actual Primary Completion Date
:
Nov 1, 2013
Actual Study Completion Date
:
Jan 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MM-121 plus Gemcitabine escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle |
Drug: MM-121
MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV
Other Names:
Drug: Gemcitabine
administered IV at 1000 mg/m2 or 1250 mg/m2
Other Names:
|
| Experimental: MM-121 plus Carboplatin carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle |
Drug: MM-121
MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV
Other Names:
Drug: Carboplatin
administered at AUC 6
|
| Experimental: MM-121 plus Pemetrexed pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle |
Drug: MM-121
MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV
Other Names:
Drug: Pemetrexed
administered IV at 500 mg/m2
Other Names:
|
| Experimental: MM-121 plus Cabazitaxel escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle |
Drug: MM-121
MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV
Other Names:
Drug: Cabazitaxel
administered IV at 20 mg/m2 or 25 mg/m2
Other Names:
|
Outcome Measures
Primary Outcome Measures
- To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies [From date of first dose to 30 days after termination, the longest 88.1 weeks]
Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses [From date of first dose to 30 days after termination, the longest 88.1 weeks]
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 Pemetrexed doses tested: 500 mg/m2 Day 1 Carboplatin doses tested: 5 or 6 AUC Day 1 Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine [From date of first dose to 30 days after termination, the longest 88.1 weeks]
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin [From date of first dose to 30 days after termination, the longest 88.1 weeks]
Maximum Tolerated Dose reported in Target AUC, as calculated by the Calvert Formula Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Carboplatin doses tested: 5 or 6 AUC Day 1
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed [From date of first dose to 30 days after termination, the longest 88.1 weeks]
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Pemetrexed doses tested: 500 mg/m2 Day 1
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel [From date of first dose to 30 days after termination, the longest 88.1 weeks]
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3
- To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies [From date of first dose to 30 days after termination, the longest 88.1 weeks]
To establish the safety of escalating doses of MM-121 administered in combination with multiple anti-cancer therapies 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 be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.
Secondary Outcome Measures
- Objective Response Rate [patients were assessed for response during their time on study, the longest of which was 88.1 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.
- Pharmacokinetics [Collections taken at Cycle 1, Week 1 for all patients at start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion]
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 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg).
- Pharmacokinetics (AUClast) [Collections taken at Cycle 1, Week 1 for all patients at the start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion]
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 AUClast. 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 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2).
- Immunogenicity [Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 88.1 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:
-
Advanced-stage solid tumors
-
≥ 18 years of age
-
Adequate liver and kidney function
Exclusion Criteria:
-
Any other active malignancy
-
No known HIV, Hepatitis C or B
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lafayette | Indiana | United States | 47905 | |
| 2 | Buffalo | New York | United States | 14263 | |
| 3 | Cincinnati | Ohio | United States | 45267 | |
| 4 | Philadelphia | Pennsylvania | United States | 19111 | |
| 5 | Villejuif | France |
Sponsors and Collaborators
- Merrimack Pharmaceuticals
- Sanofi
Investigators
- Study Director: Victor Moyo, MD, Merrimack Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01447225
Other Study ID Numbers:
- MM-121-06-01-06 (TCD11694)
First Posted:
Oct 6, 2011
Last Update Posted:
Sep 14, 2016
Last Verified:
Sep 1, 2016
Keywords provided by Merrimack Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MM-121 Plus Gemcitabine: Cohort 1 | MM-121 Plus Gemcitabine: Cohort 2 | MM-121 Plus Carboplatin: Cohort 1 | MM-121 Plus Carboplatin: Cohort 2 | MM-121 Plus Carboplatin: Cohort 3 | MM-121 Plus Pemetrexed: Cohort 1 | MM-121 Plus Pemetrexed: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 1 | MM-121 Plus Cabazitaxel: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 3 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 20 mg/kg one-time loading dose on Cycle 1, Week 1 followed 12 mg/kg IV maintenance doses weekly for 3-week cycles gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 3-week cycle | MM-121 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Gemcitabine: 1000 mg/m2 IV on Day 1 And Day 8 of each 3-week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 6 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12mg/kg IV maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 25 mg/m2 IV on Day 1 of each 3-week cycle |
| Period Title: Overall Study | ||||||||||
| STARTED | 3 | 8 | 5 | 3 | 3 | 3 | 7 | 4 | 3 | 4 |
| COMPLETED | 3 | 8 | 5 | 3 | 3 | 3 | 7 | 4 | 3 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | MM-121 Plus Gemcitabine | MM-121 Plus Carboplatin | MM-121 Plus Pemetrexed | MM-121 Plus Cabazitaxel | Total |
|---|---|---|---|---|---|
| Arm/Group Description | escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV | carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Carboplatin: administered at AUC 6 | pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Pemetrexed: administered IV at 500 mg/m2 | escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Cabazitaxel: administered IV at 20 mg/m2 or 25 mg/m2 | Total of all reporting groups |
| Overall Participants | 11 | 11 | 10 | 11 | 43 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
58.3
(7.79)
|
62.7
(9.18)
|
60.0
(12.29)
|
64.1
(6.66)
|
61.28
(8.98)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
8
72.7%
|
5
45.5%
|
7
70%
|
2
18.2%
|
22
51.2%
|
| Male |
3
27.3%
|
6
54.5%
|
3
30%
|
9
81.8%
|
21
48.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
| Not Hispanic or Latino |
10
90.9%
|
11
100%
|
10
100%
|
11
100%
|
42
97.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
| Asian |
0
0%
|
0
0%
|
1
10%
|
0
0%
|
1
2.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
10
90.9%
|
11
100%
|
9
90%
|
11
100%
|
41
95.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
8
72.7%
|
11
100%
|
7
70%
|
8
72.7%
|
34
79.1%
|
| France |
3
27.3%
|
0
0%
|
3
30%
|
3
27.3%
|
9
20.9%
|
Outcome Measures
| Title | To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies |
|---|---|
| Description | Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting |
| Time Frame | From date of first dose to 30 days after termination, the longest 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 Plus Gemcitabine: Cohort 1 | MM-121 Plus Gemcitabine: Cohort 2 | MM-121 Plus Carboplatin: Cohort 1 | MM-121 Plus Carboplatin: Cohort 2 | MM-121 Plus Carboplatin: Cohort 3 | MM-121 Plus Pemetrexed: Cohort 1 | MM-121 Plus Pemetrexed: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 1 | MM-121 Plus Cabazitaxel: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 3 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 20 mg/kg one-time loading dose on Cycle 1, Week 1 followed 12 mg/kg IV maintenance doses weekly for 3-week cycles gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 3-week cycle | MM-121 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Gemcitabine: 1000 mg/m2 IV on Day 1 And Day 8 of each 3-week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 6 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12mg/kg IV maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 25 mg/m2 IV on Day 1 of each 3-week cycle |
| Measure Participants | 3 | 8 | 5 | 3 | 3 | 3 | 7 | 4 | 3 | 4 |
| Number [participants reporting adverse events] |
3
27.3%
|
8
72.7%
|
5
50%
|
3
27.3%
|
3
7%
|
3
NaN
|
7
NaN
|
4
NaN
|
3
NaN
|
4
NaN
|
| Title | To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses |
|---|---|
| Description | Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 Pemetrexed doses tested: 500 mg/m2 Day 1 Carboplatin doses tested: 5 or 6 AUC Day 1 Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3 |
| Time Frame | From date of first dose to 30 days after termination, the longest 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note: data provided below is for MM-121 doses only for the combination. Combination therapy MTDs are provided in separate endpoint measures. |
| Arm/Group Title | MM-121 Plus Gemcitabine | MM-121 Plus Carboplatin | MM-121 Plus Pemetrexed | MM-121 Plus Cabazitaxel |
|---|---|---|---|---|
| Arm/Group Description | escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Gemcitabine: administered IV at 1000 mg/m2 or 1250 mg/m2 | carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Carboplatin: administered at AUC 6 | pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Pemetrexed: administered IV at 500 mg/m2 | escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Cabazitaxel: administered IV at 20 mg/m2 or 25 mg/m2 |
| Measure Participants | 11 | 11 | 10 | 11 |
| one-time loading dose |
40
|
40
|
40
|
40
|
| maintenance dose |
20
|
20
|
20
|
20
|
| Title | To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine |
|---|---|
| Description | Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 |
| Time Frame | From date of first dose to 30 days after termination, the longest 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| NOTE: Maximum tolerated dose is for the combination of gemcitabine and MM-121. MTD of MM-121 is provided in separate endpoint. |
| Arm/Group Title | MM-121 + Gemcitabine |
|---|---|
| Arm/Group Description | |
| Measure Participants | 11 |
| Number [mg/m2] |
1000
|
| Title | To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin |
|---|---|
| Description | Maximum Tolerated Dose reported in Target AUC, as calculated by the Calvert Formula Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Carboplatin doses tested: 5 or 6 AUC Day 1 |
| Time Frame | From date of first dose to 30 days after termination, the longest 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 + Carboplatin |
|---|---|
| Arm/Group Description | MTD of the MM-121 + Carboplatin combination NOTE: MTD of MM-121 for this combination provided in separate endpoint |
| Measure Participants | 11 |
| Number [target AUC (mg*min/mL)] |
5
|
| Title | To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed |
|---|---|
| Description | Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Pemetrexed doses tested: 500 mg/m2 Day 1 |
| Time Frame | From date of first dose to 30 days after termination, the longest 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 + Pemetrexed |
|---|---|
| Arm/Group Description | MTD of combination of MM-121 + Pemetrexed - NOTE: MTD of MM-121 for this combination provided in separate endpoint |
| Measure Participants | 10 |
| Number [mg/m2] |
500
|
| Title | To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel |
|---|---|
| Description | Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3 |
| Time Frame | From date of first dose to 30 days after termination, the longest 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 + Cabazitaxel |
|---|---|
| Arm/Group Description | MTD of MM-121 + Cabazitaxel combination - NOTE: MTD of MM-121 for this combination provided in separate endpoint |
| Measure Participants | 11 |
| Number [mg/m2] |
25
|
| Title | To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies |
|---|---|
| Description | To establish the safety of escalating doses of MM-121 administered in combination with multiple anti-cancer therapies 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 be used for the expansion cohort. DLTs were not measured in the Expansion Cohort. |
| Time Frame | From date of first dose to 30 days after termination, the longest 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 Plus Gemcitabine: Cohort 1 | MM-121 Plus Gemcitabine: Cohort 2 | MM-121 Plus Carboplatin: Cohort 1 | MM-121 Plus Carboplatin: Cohort 2 | MM-121 Plus Carboplatin: Cohort 3 | MM-121 Plus Pemetrexed: Cohort 1 | MM-121 Plus Pemetrexed: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 1 | MM-121 Plus Cabazitaxel: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 3 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 20 mg/kg one-time loading dose on Cycle 1, Week 1 followed 12 mg/kg IV maintenance doses weekly for 3-week cycles gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 3-week cycle | MM-121 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Gemcitabine: 1000 mg/m2 IV on Day 1 And Day 8 of each 3-week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 6 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12mg/kg IV maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 25 mg/m2 IV on Day 1 of each 3-week cycle |
| Measure Participants | 3 | 8 | 5 | 3 | 3 | 3 | 7 | 4 | 3 | 3 |
| Number [participants reporting DLTs] |
0
0%
|
1
9.1%
|
1
10%
|
0
0%
|
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | 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 88.1 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 Plus Gemcitabine: Cohort 1 | MM-121 Plus Gemcitabine: Cohort 2 | MM-121 Plus Carboplatin: Cohort 1 | MM-121 Plus Carboplatin: Cohort 2 | MM-121 Plus Carboplatin: Cohort 3 | MM-121 Plus Pemetrexed: Cohort 1 | MM-121 Plus Pemetrexed: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 1 | MM-121 Plus Cabazitaxel: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 3 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 20 mg/kg one-time loading dose on Cycle 1, Week 1 followed 12 mg/kg IV maintenance doses weekly for 3-week cycles gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 3-week cycle | MM-121 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Gemcitabine: 1000 mg/m2 IV on Day 1 And Day 8 of each 3-week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 6 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12mg/kg IV maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 25 mg/m2 IV on Day 1 of each 3-week cycle |
| Measure Participants | 3 | 8 | 5 | 3 | 3 | 3 | 7 | 4 | 3 | 4 |
| Number [participants with objective response] |
0
0%
|
2
18.2%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
1
NaN
|
1
NaN
|
2
NaN
|
1
NaN
|
| Title | Pharmacokinetics |
|---|---|
| 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 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg). |
| Time Frame | Collections taken at Cycle 1, Week 1 for all patients at start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 + Gemcitabine: 20/12 mg/kg | MM-121 + Carboplatin: 20/12 mg/kg | MM-121 + Pemetrexed: 20/12 mg/kg | MM-121 + Cisplatin: 20/12 mg/kg | MM-121 + Gemcitabine: 40/20 mg/kg | MM-121 + Carboplatin: 40/20 mg/kg | MM-121 + Pemetrexed: 40/20 mg/kg | MM-121 + Cisplatin: 40/20 mg/kg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose plus gemcitabine 1000mg/m² or 1250mg/m² | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus carboplatin AUC 6 | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus pemetrexed 500 mg/m² | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus Cisplatin 20 mg/m2 or 25 mg/m2 | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose plus gemcitabine 1000mg/m² or 1250mg/m² | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus carboplatin AUC 6 | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus pemetrexed 500 mg/m² | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus Cisplatin 25 mg/m2 |
| Measure Participants | 3 | 8 | 3 | 4 | 8 | 3 | 7 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [ug/mL] |
560
(45.2)
|
554.8
(30.2)
|
900.7
(37.6)
|
677.1
(24.0)
|
1033.4
(24.2)
|
1107.2
(18.3)
|
1100.8
(18.0)
|
1087.9
(18.2)
|
| Title | Pharmacokinetics (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 AUClast. 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 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2). |
| Time Frame | Collections taken at Cycle 1, Week 1 for all patients at the start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MM-121 + Gemcitabine: 20/12 mg/kg | MM-121 + Carboplatin: 20/12 mg/kg | MM-121 + Pemetrexed: 20/12 mg/kg | MM-121 + Cisplatin: 20/12 mg/kg | MM-121 + Gemcitabine: 40/20 mg/kg | MM-121 + Carboplatin: 40/20 mg/kg | MM-121 + Pemetrexed: 40/20 mg/kg | MM-121 + Cisplatin: 40/20 mg/kg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose plus gemcitabine 1000mg/m² or 1250mg/m² | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus carboplatin AUC 6 | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus pemetrexed 500 mg/m² | MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus Cisplatin 20 mg/m2 or 25 mg/m2 | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose plus gemcitabine 1000mg/m² or 1250mg/m² | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus carboplatin AUC 6 | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus pemetrexed 500 mg/m² | MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus Cisplatin 25 mg/m2 |
| Measure Participants | 3 | 8 | 3 | 4 | 8 | 3 | 7 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [hr* ug/mL] |
39666.4
(41.0)
|
49749.6
(41.3)
|
59984.1
(36.9)
|
51995.1
(71.1)
|
72132.1
(41.9)
|
100309.9
(34.2)
|
92732.9
(31.1)
|
98142.6
(18.0)
|
| 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 88.1 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 | MM-121 Plus Gemcitabine: Cohort 1 | MM-121 Plus Gemcitabine: Cohort 2 | MM-121 Plus Carboplatin: Cohort 1 | MM-121 Plus Carboplatin: Cohort 2 | MM-121 Plus Carboplatin: Cohort 3 | MM-121 Plus Pemetrexed: Cohort 1 | MM-121 Plus Pemetrexed: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 1 | MM-121 Plus Cabazitaxel: Cohort 2 | MM-121 Plus Cabazitaxel: Cohort 3 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MM-121 20 mg/kg one-time loading dose on Cycle 1, Week 1 followed 12 mg/kg IV maintenance doses weekly for 3-week cycles gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 3-week cycle | MM-121 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Gemcitabine: 1000 mg/m2 IV on Day 1 And Day 8 of each 3-week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 6 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle Carboplatin at AUC 5 Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance dose weekly for every 3-week cycle Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle | MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12mg/kg IV maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle | MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle Cabazitaxel: 25 mg/m2 IV on Day 1 of each 3-week cycle |
| Measure Participants | 3 | 8 | 5 | 3 | 3 | 3 | 7 | 4 | 3 | 4 |
| Number |
NA
|
NA
|
NA
|
NA
|
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 Plus Gemcitabine | MM-121 Plus Carboplatin | MM-121 Plus Pemetrexed | MM-121 Plus Cabazitaxel | ||||
| Arm/Group Description | escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV | carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Carboplatin: administered at AUC 6 | pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Pemetrexed: administered IV at 500 mg/m2 | escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV Cabazitaxel: administered IV at 20 mg/m2 or 25 mg/m2 | ||||
All Cause Mortality |
||||||||
| MM-121 Plus Gemcitabine | MM-121 Plus Carboplatin | MM-121 Plus Pemetrexed | MM-121 Plus Cabazitaxel | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| MM-121 Plus Gemcitabine | MM-121 Plus Carboplatin | MM-121 Plus Pemetrexed | MM-121 Plus Cabazitaxel | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/11 (81.8%) | 7/11 (63.6%) | 3/10 (30%) | 2/11 (18.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| THROMBOCYTOPENIA | 1/11 (9.1%) | 2/11 (18.2%) | 0/10 (0%) | 0/11 (0%) | ||||
| THROMBOTIC MICROANGIOPATHY | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| FEBRILE NEUTROPENIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Cardiac disorders | ||||||||
| ACUTE CORONARY SYNDROME | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| ATRIAL FIBRILLATION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| ANGINA PECTORIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Gastrointestinal disorders | ||||||||
| DIARRHOEA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| OESOPHAGEAL RUPTURE | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| VOMITING | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| General disorders | ||||||||
| DISEASE PROGRESSION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| BILE DUCT OBSTRUCTION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| Infections and infestations | ||||||||
| CELLULITIS | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| URINARY TRACT INFECTION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| ABSCESS LIMB | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| CLOSTRIDIAL INFECTION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| GROIN ABSCESS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| DEVICE RELATED INFECTION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| ERYSIPELAS | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| HUMERUS FRACTURE | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| DEHYDRATION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Nervous system disorders | ||||||||
| ATAXIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| CEREBROVASCULAR ACCIDENT | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| HAEMORRHAGE INTRACRANIAL | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| ACUTE RESPIRATORY DISTRESS SYNDROME | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| PULMONARY EMBOLISM | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| PNEUMONIA ASPIRATION | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Surgical and medical procedures | ||||||||
| CENTRAL VENOUS CATHETER REMOVAL | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Vascular disorders | ||||||||
| HYPOTENSION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| DEEP VEIN THROMBOSIS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| EMBOLISM | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| MM-121 Plus Gemcitabine | MM-121 Plus Carboplatin | MM-121 Plus Pemetrexed | MM-121 Plus Cabazitaxel | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/11 (100%) | 11/11 (100%) | 10/10 (100%) | 11/11 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 7/11 (63.6%) | 5/11 (45.5%) | 4/10 (40%) | 6/11 (54.5%) | ||||
| NEUTROPENIA | 4/11 (36.4%) | 0/11 (0%) | 3/10 (30%) | 4/11 (36.4%) | ||||
| THROMBOCYTOPENIA | 4/11 (36.4%) | 5/11 (45.5%) | 1/10 (10%) | 4/11 (36.4%) | ||||
| LEUKOPENIA | 2/11 (18.2%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| LYMPHOPENIA | 2/11 (18.2%) | 0/11 (0%) | 1/10 (10%) | 3/11 (27.3%) | ||||
| LYMPHADENOPATHY | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| THROMBOTIC MICROANGIOPATHY | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| FEBRILE NEUTROPENIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| LEUKOCYTOSIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| SPLENOMEGALY | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Cardiac disorders | ||||||||
| PALPITATIONS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| ATRIAL FIBRILLATION | 0/11 (0%) | 1/11 (9.1%) | 1/10 (10%) | 0/11 (0%) | ||||
| ACUTE CORONARY SYNDROME | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| TACHYCARDIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| ANGINA PECTORIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Endocrine disorders | ||||||||
| HYPOTHYROIDISM | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| Eye disorders | ||||||||
| DRY EYE | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| LACRIMATION INCREASED | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| BLEPHAROSPASM | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| BLINDNESS UNILATERAL | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| CATARACT | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| CONJUNCTIVITIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| EYE INFLAMMATION | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Gastrointestinal disorders | ||||||||
| NAUSEA | 7/11 (63.6%) | 8/11 (72.7%) | 4/10 (40%) | 7/11 (63.6%) | ||||
| DIARRHOEA | 6/11 (54.5%) | 9/11 (81.8%) | 7/10 (70%) | 11/11 (100%) | ||||
| VOMITING | 6/11 (54.5%) | 6/11 (54.5%) | 2/10 (20%) | 3/11 (27.3%) | ||||
| CONSTIPATION | 4/11 (36.4%) | 2/11 (18.2%) | 2/10 (20%) | 2/11 (18.2%) | ||||
| ABDOMINAL PAIN | 3/11 (27.3%) | 1/11 (9.1%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| ABDOMINAL PAIN UPPER | 0/11 (0%) | 2/11 (18.2%) | 2/10 (20%) | 1/11 (9.1%) | ||||
| STOMATITIS | 3/11 (27.3%) | 1/11 (9.1%) | 2/10 (20%) | 4/11 (36.4%) | ||||
| ABDOMINAL RIGIDITY | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| APHTHOUS STOMATITIS | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| GASTRITIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| HAEMORRHOIDS | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| HIATUS HERNIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| OESOPHAGEAL STENOSIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| FLATULENCE | 0/11 (0%) | 2/11 (18.2%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| ASCITES | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| BREATH ODOR | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| DYSPHAGIA | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| GASTROINTESTINAL PAIN | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| GASTROESOPHAGEAL REFLUX DISEASE | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 3/11 (27.3%) | ||||
| ODYNOPHAGIA | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| OESOPHAGEAL RUPTURE | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| HAEMATOCHEZIA | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| PAINFUL DEFAECATION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| RECTAL HAEMORRHAGE | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| ABDOMINAL DISTENSION | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| DRY MOUTH | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| DYSPEPSIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| CHAPPED LIPS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| General disorders | ||||||||
| FATIGUE | 5/11 (45.5%) | 6/11 (54.5%) | 7/10 (70%) | 5/11 (45.5%) | ||||
| OEDEMA PERIPHERAL | 4/11 (36.4%) | 2/11 (18.2%) | 4/10 (40%) | 3/11 (27.3%) | ||||
| PYREXIA | 4/11 (36.4%) | 1/11 (9.1%) | 2/10 (20%) | 1/11 (9.1%) | ||||
| MUCOSAL INFLAMMATION | 3/11 (27.3%) | 1/11 (9.1%) | 1/10 (10%) | 4/11 (36.4%) | ||||
| ASTHENIA | 2/11 (18.2%) | 0/11 (0%) | 3/10 (30%) | 5/11 (45.5%) | ||||
| CHILLS | 1/11 (9.1%) | 0/11 (0%) | 2/10 (20%) | 2/11 (18.2%) | ||||
| INFLUENZA LIKE ILLNESS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 3/11 (27.3%) | ||||
| NON-CARDIAC CHEST PAIN | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| OEDEMA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| PAIN | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| SUPRAPUBIC PAIN | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| XEROSIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| CATHETER SITE RASH | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| DISEASE PROGRESSION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| CHEST PAIN | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| INJECTION SITE HAEMORRHAGE | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| EARLY SATIETY | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| GAIT DISTURBANCE | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| INJECTION SITE PAIN | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Hepatobiliary disorders | ||||||||
| BILE DUCT OBSTRUCTION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| CYTOLYTIC HEPATITIS | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| HEPATOBILIARY DISEASE | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| HYPERTRANSAMINASAEMIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| Infections and infestations | ||||||||
| URINARY TRACT INFECTION | 4/11 (36.4%) | 3/11 (27.3%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| CELLULITIS | 2/11 (18.2%) | 0/11 (0%) | 1/10 (10%) | 2/11 (18.2%) | ||||
| ORAL FUNGAL INFECTION | 2/11 (18.2%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| PNEUMONIA | 2/11 (18.2%) | 0/11 (0%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| UPPER RESPIRATORY TRACT INFECTION | 2/11 (18.2%) | 2/11 (18.2%) | 0/10 (0%) | 4/11 (36.4%) | ||||
| EAR INFECTION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| FUNGAL SKIN INFECTION | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| GASTROENTERITIS VIRAL | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| PYELONEPHRITIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| RASH PUSTULAR | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| RHINITIS | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| SINUSITIS | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| TINEA PEDIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| ABSCESS LIMB | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| BRONCHITIS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| CLOSTRIDIAL INFECTION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| CLOSTRIDIUM DIFFICILE COLITIS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| GROIN ABSCESS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| LOBAR PNEUMONIA | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| ORAL CANDIDIASIS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| STAPHYLOCOCCAL INFECTION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| DEVICE RELATED INFECTION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| ERYSIPELAS | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| FUNGAL INFECTION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| PARONYCHIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 3/11 (27.3%) | ||||
| FOLLICULITIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| OTITIS MEDIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| URETERITIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| HUMERUS FRACTURE | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| WOUND COMPLICATION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| WOUND HAEMORRHAGE | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| CONTUSION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| INFUSION RELATED REACTION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| LACERATION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| PROCEDURAL PAIN | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| EXCORIATION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| ANIMAL BITE | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| SNAKE BITE | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Investigations | ||||||||
| INTERNATIONAL NORMALISED RATIO INCREASED | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| NEUTROPHIL COUNT INCREASED | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| WEIGHT DECREASED | 1/11 (9.1%) | 4/11 (36.4%) | 1/10 (10%) | 0/11 (0%) | ||||
| WHITE BLOOD CELL COUNT DECREASED | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| BLOOD CREATININE INCREASED | 0/11 (0%) | 1/11 (9.1%) | 1/10 (10%) | 0/11 (0%) | ||||
| LYMPHOCYTE COUNT DECREASED | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| ALANINE AMINOTRANSFERASE INCREASED | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| ELECTROCARDIOGRAM QT PROLONGED | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| PLATELET COUNT DECREASED | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| URINE OUTPUT DECREASED | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Metabolism and nutrition disorders | ||||||||
| DECREASED APPETITE | 4/11 (36.4%) | 3/11 (27.3%) | 3/10 (30%) | 4/11 (36.4%) | ||||
| HYPOKALAEMIA | 4/11 (36.4%) | 2/11 (18.2%) | 3/10 (30%) | 6/11 (54.5%) | ||||
| HYPOPHOSPHATAEMIA | 4/11 (36.4%) | 2/11 (18.2%) | 1/10 (10%) | 7/11 (63.6%) | ||||
| DEHYDRATION | 3/11 (27.3%) | 1/11 (9.1%) | 1/10 (10%) | 4/11 (36.4%) | ||||
| HYPOALBUMINAEMIA | 2/11 (18.2%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| HYPOMAGNESAEMIA | 2/11 (18.2%) | 3/11 (27.3%) | 2/10 (20%) | 3/11 (27.3%) | ||||
| HYPONATRAEMIA | 2/11 (18.2%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| HYPERGLYCAEMIA | 1/11 (9.1%) | 0/11 (0%) | 2/10 (20%) | 2/11 (18.2%) | ||||
| HYPOCALCAEMIA | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| GOUT | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| HYPOGLYCEMIA | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| HYPERURICAEMIA | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| MALNUTRITION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| HYPERKALAEMIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| HYPERLIPIDAEMIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| HYPERNATRAEMIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| POLYDIPSIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| MYALGIA | 2/11 (18.2%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| ARTHRALGIA | 1/11 (9.1%) | 1/11 (9.1%) | 1/10 (10%) | 2/11 (18.2%) | ||||
| MUSCLE SPASMS | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 4/11 (36.4%) | ||||
| MUSCULOSKELETAL PAIN | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| COSTOCHONDRITIS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| FLANK PAIN | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| MUSCULOSKELETAL CHEST PAIN | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| BONE PAIN | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 2/11 (18.2%) | ||||
| SPINAL OSTEOARTHRITIS | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| BACK PAIN | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 4/11 (36.4%) | ||||
| PAIN IN EXTREMITY | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 3/11 (27.3%) | ||||
| Nervous system disorders | ||||||||
| DIZZINESS | 2/11 (18.2%) | 0/11 (0%) | 1/10 (10%) | 5/11 (45.5%) | ||||
| AGEUSIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| ATAXIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| CONVULSION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| HEADACHE | 1/11 (9.1%) | 3/11 (27.3%) | 0/10 (0%) | 4/11 (36.4%) | ||||
| LOSS OF CONSCIOUSNESS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| NEUROLOGICAL SYMPTOM | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| NEUROPATHY PERIPHERAL | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 5/11 (45.5%) | ||||
| PARAESTHESIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| TREMOR | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| CEREBROVASCULAR ACCIDENT | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| DYSGEUSIA | 0/11 (0%) | 1/11 (9.1%) | 1/10 (10%) | 4/11 (36.4%) | ||||
| HAEMORRHAGE INTRACRANIAL | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| SOMNOLENCE | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| DIZZINESS POSTURAL | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| HYPOAESTHESIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| MEMORY IMPAIRMENT | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| SYNCOPE | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Psychiatric disorders | ||||||||
| CONFUSIONAL STATE | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| INSOMNIA | 1/11 (9.1%) | 3/11 (27.3%) | 3/10 (30%) | 2/11 (18.2%) | ||||
| DEPRESSION | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Renal and urinary disorders | ||||||||
| HAEMATURIA | 2/11 (18.2%) | 2/11 (18.2%) | 0/10 (0%) | 3/11 (27.3%) | ||||
| POLLAKIURIA | 2/11 (18.2%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| PROTEINURIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 3/11 (27.3%) | ||||
| URINARY INCONTINENCE | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| DYSURIA | 0/11 (0%) | 2/11 (18.2%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| BLADDER PAIN | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| RENAL INJURY | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| HYDRONEPHROSIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 3/11 (27.3%) | ||||
| CYSTITIS NONINFECTIVE | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| LEUKOCYTURIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| POLYURIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| RENAL FAILURE | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Reproductive system and breast disorders | ||||||||
| SCROTAL DISORDER | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| PENIS DISORDER | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| COUGH | 4/11 (36.4%) | 1/11 (9.1%) | 2/10 (20%) | 1/11 (9.1%) | ||||
| DYSPNOEA | 4/11 (36.4%) | 0/11 (0%) | 1/10 (10%) | 4/11 (36.4%) | ||||
| EPISTAXIS | 3/11 (27.3%) | 0/11 (0%) | 3/10 (30%) | 2/11 (18.2%) | ||||
| PULMONARY EMBOLISM | 2/11 (18.2%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| ACUTE RESPIRATORY DISTRESS SYNDROME | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| DYSPHONIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| HAEMOPTYSIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| NASAL DRYNESS | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| OROPHARYNGEAL PAIN | 1/11 (9.1%) | 1/11 (9.1%) | 1/10 (10%) | 0/11 (0%) | ||||
| PLEURAL EFFUSION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| RHINITIS ALLERGIC | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| WHEEZING | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| RHINORRHOEA | 0/11 (0%) | 1/11 (9.1%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| SINUS CONGESTION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| RESPIRATORY TRACT CONGESTION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| DYSPNOAE EXERTIONAL | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| HYPOXIA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| NASAL CONGESTION | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| NOCTURNAL DYSPNOEA | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| PNEUMONIA ASPIRATION | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| ALOPECIA | 2/11 (18.2%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| DRY SKIN | 2/11 (18.2%) | 0/11 (0%) | 2/10 (20%) | 2/11 (18.2%) | ||||
| RASH | 2/11 (18.2%) | 1/11 (9.1%) | 3/10 (30%) | 3/11 (27.3%) | ||||
| DERMATITIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| ERYTHEMA | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| HYPERHIDROSIS | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| NIGHT SWEATS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| ONYCHOLYSIS | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| PRURITUS | 1/11 (9.1%) | 0/11 (0%) | 2/10 (20%) | 0/11 (0%) | ||||
| RASH MACULAR | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| RASH MACULO-PAPULAR | 1/11 (9.1%) | 2/11 (18.2%) | 0/10 (0%) | 2/11 (18.2%) | ||||
| SKIN HYPERPIGMENTATION | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| SKIN IRRITATION | 1/11 (9.1%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| TELANGIECTASIA | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| SKIN INDURATION | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| SKIN ULCER | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| PHOTOSENSITIVITY REACTION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| SKIN LESION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| ACNE | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| DERMATITIS ACNEFORM | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| NAIL RIDGING | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| ONYCHOMADESIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| ONYCHOCLASIS | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Surgical and medical procedures | ||||||||
| SINUS OPERATION | 0/11 (0%) | 1/11 (9.1%) | 1/10 (10%) | 0/11 (0%) | ||||
| CENTRAL VENOUS CATHETER REMOVAL | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Vascular disorders | ||||||||
| HAEMORRHAGE | 1/11 (9.1%) | 0/11 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| HYPOTENSION | 1/11 (9.1%) | 0/11 (0%) | 1/10 (10%) | 1/11 (9.1%) | ||||
| DEEP VEIN THROMBOSIS | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| EMBOLISM | 0/11 (0%) | 1/11 (9.1%) | 0/10 (0%) | 0/11 (0%) | ||||
| FLUSHING | 0/11 (0%) | 1/11 (9.1%) | 1/10 (10%) | 0/11 (0%) | ||||
| HAEMATOMA | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| HYPERTENSION | 0/11 (0%) | 0/11 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| ORTHOSTATIC HYPOTENSION | 0/11 (0%) | 0/11 (0%) | 0/10 (0%) | 3/11 (27.3%) | ||||
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:
NCT01447225
Other Study ID Numbers:
- MM-121-06-01-06 (TCD11694)
First Posted:
Oct 6, 2011
Last Update Posted:
Sep 14, 2016
Last Verified:
Sep 1, 2016