A Safety Study of MM-121 With Cetuximab and Irinotecan in Patients With Advanced Cancers

NCT01451632 | Completed Phase 1 Results

• 1 other identifier: MM-121-05-01-05 (TCD11696)
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study was to evaluate the safety and tolerability of escalating doses of the MM-121 plus cetuximab and the MM-121 plus cetuximab plus irinotecan combination.

Conditions

Colorectal Cancer; Squamous Cell Head and Neck Cancer; Non-small Cell Lung Cancer; Triple Negative Breast Cancer; Other Tumors With EGFR Dependence

Keywords

Metastatic Colorectal cancer; Kras wild-type; Squamous cell head and neck cancer; Non-small cell lung cancer; Triple negative breast cancer; EGFR; ErbB3; MM-121; Cetuximab; Irinotecan

Outcome Measures

Primary Outcomes (3)

• Dose Escalation: To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Plus Cetuximab and the MM-121 Plus Cetuximab Plus Irinotecan Combination

  To establish the safety of escalating doses of MM-121 in combination with cetuximab or in combination with cetuximab and irinotecan 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.

  From date of first dose to 30 days after termination, the longest 48.1 weeks

• To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s) (Via Recording of Maximum Tolerated Dose (MTD)): MM-121 Doses

  Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. RP2D = one dose lever lower than the MTD Part 1: Cohort 1: MM-121: 12 mg/kg MM-121 QW + Cetuximab: 400 mg/m2 loading dose/200 mg/m2 (400/200) QW maintenance Cohort 2a: MM-121: 20 mg/kg IV QW + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 2b: MM-121: 12 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 3a: MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW (40/20) + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 3b: MM-121 20 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 4: MM-121: 40/20 mg/kg IV QW + Cetuximab: 400 / 250 mg/m2 maintenance IV QW Part 2: Cohort 1: MM-121: 20 mg/kg IV QW + Cetuximab: 400/200 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2 IV Q2W Cohort 2: MM-121: 40 / 20 mg/kg IV QW + Cetuximab: 400/250 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2

  From date of first dose to 30 days after termination, the longest 48.1 weeks

• To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s): Cetuximab and Irinotecan

  Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. RP2D = one dose lever lower than the MTD Part 1: Cohort 1: MM-121: 12 mg/kg MM-121 QW + Cetuximab: 400 mg/m2 loading dose/200 mg/m2 (400/200) QW maintenance Cohort 2a: MM-121: 20 mg/kg IV QW + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 2b: MM-121: 12 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 3a: MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW (40/20) + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 3b: MM-121 20 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 4: MM-121: 40/20 mg/kg IV QW + Cetuximab: 400 / 250 mg/m2 maintenance IV QW Part 2: Cohort 1: MM-121: 20 mg/kg IV QW + Cetuximab: 400/200 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2 IV Q2W Cohort 2: MM-121: 40 / 20 mg/kg IV QW + Cetuximab: 400/250 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2

  From date of first dose to 30 days after termination, the longest 48.1 weeks

Secondary Outcomes (4)

• Objective Response Rate

  Patients were assessed for objective response from time of first dose through treatment termination, the longest treatment duration being 48.1 weeks

• Pharmacokinetics

  Collections taken for all patients at Cycle 1, Week 1 at pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121

• Pharmacokinetic Parameters of MM-121

  Collections taken for all patients at Cycle 1, Week 1 at pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121

• Immunogenicity

  Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 48.1 weeks, and a collection was made post-infusion in any case of infusion reaction

Study Arms (2)

Part 1: MM-121 + cetuximab

EXPERIMENTAL

increasing doses of weekly MM-121 + weekly cetuximab

Drug: MM-121; Drug: Cetuximab

Part 2: MM-121 + cetuximab + irinotecan

EXPERIMENTAL

increasing doses of irinotecan + the Recommended Phase 2 Dose/Maximum Tolerated Dose (RP2D/MTD) of MM121 + cetuximab as determined in Part 1

Drug: MM-121; Drug: Irinotecan; Drug: Cetuximab

Interventions

MM-121 DRUG

escalating doses MM-121 IV QW

Also known as: Seribantumab, SAR256212

Part 1: MM-121 + cetuximab; Part 2: MM-121 + cetuximab + irinotecan

Irinotecan DRUG

180 mg/m2 IV Q2W

Also known as: Camptosar

Part 2: MM-121 + cetuximab + irinotecan

Cetuximab DRUG

escalating doses cetuximab IV QW

Also known as: Erbitux

Part 1: MM-121 + cetuximab; Part 2: MM-121 + cetuximab + irinotecan

Eligibility Criteria

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

You may qualify if:

• No standard options remaining
• Adequate liver and kidney functions
• years of age or above

You may not qualify if:

• History of any secondary active cancer in the last 3 years.
• Pregnant or breast feeding
• History of severe allergic reactions or contraindications to cetuximab or irinotecan

Sponsors & Collaborators

• Merrimack Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (4)

Unknown Facility

San Francisco, California, 94115, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

Unknown Facility

Chapel Hill, North Carolina, 27599, United States

Location

Unknown Facility

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Head and Neck Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms

Interventions

seribantumab; Irinotecan; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2011
• First Posted: October 13, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: June 1, 2014
• Last Updated: September 8, 2016
• Results First Posted: September 8, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)