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

Study Overview
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Brief Summary
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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
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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.

Official Title
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SHERLOC: A Phase 2 Study of MM-121 in Combination With Docetaxel Versus Docetaxel Alone in Patients With Heregulin Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Merrimack Pharmaceuticals Inc.)

Conditions
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Non-Small Cell Lung Cancer, NSCLC, Adenocarcinoma, Heregulin

Intervention / Treatment
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* Drug: MM-121
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Randomized, open-label, international, multi-center, Phase 2 study in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Experimental Arm<br>MM-121 in combination with Docetaxel | Drug: MM-121<br>* Investigational, fully human antibody targeting and inhibiting ErbB3<br>* Other names: seribantumab;Drug: Docetaxel<br>* approved chemotherapy treatment for NSCLC<br>* Other names: Taxotere;|
| Active Comparator: Arm B: Comparator Arm<br>Docetaxel alone | Drug: Docetaxel<br>* approved chemotherapy treatment for NSCLC<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | 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. | Randomization until progression of disease or death due to any cause within 3 years,11 months (the study terminated prematurely) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause | From date of randomization until the date of death from any cause assessed upto 3 years,11 months (the study terminated prematurely) | 
| Objective Response Rate | 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 | Randomization through end of study up to 3 years, 11 months (the study terminated prematurely) | 
| Time to Progression | 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. | Randomization to date of objective tumor progression up to 3 years, 11 months (the study terminated prematurely) | 
| Number of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone | 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 | TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months | 
| Pharmacokinetic (PK) Parameters of MM-121 in Combination With Docetaxel and Docetaxel When Given in Combination With 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. | 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 | 
| Percentage of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone | 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 | TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Non-Small Cell Lung Cancer, heregulin, ErbB3, docetaxel