Safety Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors

NCT01447225 | Completed Phase 1 Results

• 1 other identifier: MM-121-06-01-06 (TCD11694)
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 5

Brief Summary

To evaluate the safety and tolerability of escalating doses of MM-121 + certain anticancer therapies

Conditions

Solid Tumors

Keywords

Advanced-stage; Solid Tumors; MM-121; Carboplatin; Pemetrexed; Gemcitabine; Cabazitaxel; ErbB3; Phase I; Cancer

Outcome Measures

Primary Outcomes (7)

• To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies

  Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting

  From date of first dose to 30 days after termination, the longest 88.1 weeks

• To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses

  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

  From date of first dose to 30 days after termination, the longest 88.1 weeks

• To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine

  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

  From date of first dose to 30 days after termination, the longest 88.1 weeks

• To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin

  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

  From date of first dose to 30 days after termination, the longest 88.1 weeks

• To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed

  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

  From date of first dose to 30 days after termination, the longest 88.1 weeks

• To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel

  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

  From date of first dose to 30 days after termination, the longest 88.1 weeks

• To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies

  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.

  From date of first dose to 30 days after termination, the longest 88.1 weeks

Secondary Outcomes (4)

• Objective Response Rate

  patients were assessed for response during their time on study, the longest of which was 88.1 weeks

• 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

• 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

• 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

Study Arms (4)

MM-121 plus Gemcitabine

EXPERIMENTAL

escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle

Drug: MM-121; Drug: Gemcitabine

MM-121 plus Carboplatin

EXPERIMENTAL

carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle

Drug: MM-121; Drug: Carboplatin

MM-121 plus Pemetrexed

EXPERIMENTAL

pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle

Drug: MM-121; Drug: Pemetrexed

MM-121 plus Cabazitaxel

EXPERIMENTAL

escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle

Drug: MM-121; Drug: Cabazitaxel

Interventions

MM-121 DRUG

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

Also known as: Seribantumab, SAR256212

MM-121 plus Cabazitaxel; MM-121 plus Carboplatin; MM-121 plus Gemcitabine; MM-121 plus Pemetrexed

Carboplatin DRUG

administered at AUC 6

MM-121 plus Carboplatin

Pemetrexed DRUG

administered IV at 500 mg/m2

Also known as: ALIMTA

MM-121 plus Pemetrexed

Cabazitaxel DRUG

administered IV at 20 mg/m2 or 25 mg/m2

Also known as: Jevtana

MM-121 plus Cabazitaxel

Gemcitabine DRUG

administered IV at 1000 mg/m2 or 1250 mg/m2

Also known as: Gemzar

MM-121 plus Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced-stage solid tumors
• ≥ 18 years of age
• Adequate liver and kidney function

You may not qualify if:

• Any other active malignancy
• No known HIV, Hepatitis C or B

Sponsors & Collaborators

• Merrimack Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (5)

Unknown Facility

Lafayette, Indiana, 47905, United States

Location

Unknown Facility

Buffalo, New York, 14263, United States

Location

Unknown Facility

Cincinnati, Ohio, 45267, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19111, United States

Location

Unknown Facility

Villejuif, France

Location

MeSH Terms

Conditions

Neoplasms

Interventions

seribantumab; Carboplatin; Pemetrexed; cabazitaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Clinical Trial Manager
• Organization: Merrimack Pharmaceuticals, Inc.

smathews@merrimack.com

617-441-1000

Study Officials

• Victor Moyo, MD

  Merrimack Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2011
• First Posted: October 6, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: January 1, 2014
• Last Updated: September 14, 2016
• Results First Posted: September 14, 2016

Record last verified: 2016-09

Locations

US (4); FR (1)