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A Study of MM-121 in Combination With Chemotherapy Versus Chemotherapy Alone in Heregulin Positive NSCLC

Phase 2
Terminated
Conditions
Adenocarcinoma
Non-Small Cell Lung Cancer
NSCLC
Heregulin
Interventions
Registration Number
NCT02387216
Lead Sponsor
Elevation Oncology
Brief Summary

The purpose of this study is to determine whether the combination of MM-121 plus docetaxel is more effective than docetaxel alone in regards to PFS in patients with heregulin-positive NSCLC.

Detailed Description

This study is a randomized, open-label, international, multi-center, phase 2 study in patients with Heregulin-positive NSCLC histologically classified as adenocarcinoma that have progressed following no more than two systemic therapies for locally advanced or metastatic disease, one of which must have been a platinum containing regimen. All patients will initially be screened for heregulin status. Eligible patients will be randomized to receive MM-121 in combination with docetaxel versus docetaxel alone.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
153
Inclusion Criteria
  • Patients with a diagnosis of cytologically or histologically documented adenocarcinoma of the lung with either metastatic disease (stage IV), Stage IIIB or Stage IIIC disease not amenable to surgery with curative intent
  • Not received more than 2 prior systemic therapies- one of which must have been a platinum based regimen- for primary or recurrent disease
  • Tissue submitted for HRG-biomarker testing
  • ECOG performance status (PS) of 0 or 1
Exclusion Criteria
  • Known ALK mutation
  • Presence of exon 19 deletion or exon 21 (L858R) substitution of the EGFR gene
  • Received >2 prior systemic anti-cancer drug regimen for locally advanced disease
  • Prior treatment with an anti-ErbB3 antibody
  • CTCAE grade 3 or higher peripheral neuropathy
  • Symptomatic CNS metastases or CNS metastases requiring steroids
  • Any other active malignancy requiring systemic therapy
  • Clinically significant cardiac disease

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm A: Experimental ArmMM-121MM-121 in combination with Docetaxel
Arm A: Experimental ArmDocetaxelMM-121 in combination with Docetaxel
Arm B: Comparator ArmDocetaxelDocetaxel alone
Primary Outcome Measures
NameTimeMethod
Progression Free SurvivalRandomization until progression of disease or death due to any cause within 3 years,11 months (the study terminated prematurely)

Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v.1.1, or death from any cause, whichever came first based on investigator assessment.

Patients that do not experience progression or death at the time of analysis were to be progression censored at the date of last valid tumor assessment. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method. Tumor response was evaluated by the local radiologist according to RECIST version 1.1 to establish disease progression by CT or MRI.

Secondary Outcome Measures
NameTimeMethod
Time to ProgressionRandomization to date of objective tumor progression up to 3 years, 11 months (the study terminated prematurely)

Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression. In the actual analysis, duration of response (DOR) was analysed.

Number of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel AloneTEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months

Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration

Pharmacokinetic (PK) Parameters of MM-121 in Combination With Docetaxel and Docetaxel When Given in Combination With MM-121.The study terminated prematurely after 3 years, 11 months (02 Jan 2019). PK evaluation were to be performed on samples obtained at Week 1 pre-dose and post-dose and at pre-dose at Cycle 2 and beyond to assess pre-treatment through concentrations of MM-121

Pharmacokinetic (PK) profile of MM-121 when given in combination with docetaxel, and of docetaxel when given in combination with MM-121. The maximum observed concentration (Cmax) were to be presented and calculated using non-compartmental analysis. Serum levels of MM-121 were to be measured at a central lab using an enzyme-linked immunosorbent assay.

Percentage of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel AloneTEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months

Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration

Overall SurvivalFrom date of randomization until the date of death from any cause assessed upto 3 years,11 months (the study terminated prematurely)

Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause

Objective Response RateRandomization through end of study up to 3 years, 11 months (the study terminated prematurely)

Objective Response Rate (ORR) is defined as the proportion of patients a best overall response characterised as either a Complete Response (CR) or Partial Response (PR), as defined according to RECIST v1.1 guidelines, relative to the total number of evaluable patients.

Complete Response (CR) is defined as disappearance of all lesions and pathologic lymph nodes.

Partial Response (PR) is defined as \>=30% decrease in the sum of the longest diameter of target lesions

Trial Locations

Locations (2)

CHI Creteil

🇫🇷

Créteil, Paris, France

Centre Léon Bérard

🇫🇷

Lyon cedex 08, Rhône-Alpes, France

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