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

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.)

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.

Study Overview

• Status: Terminated
• Conditions: Adenocarcinoma; Non-Small Cell Lung Cancer; NSCLC; Heregulin
• Intervention / Treatment: Drug: MM-121; Drug: Docetaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
• France
  • Paris
    • Créteil, Paris, France, 94010
      • Chi Creteil
  • Rhône-Alpes
    • Lyon cedex 08, Rhône-Alpes, France, 69317
      • Centre Léon Bérard
• Germany
  • Bad Berka, Germany, 99437
  • Berlin, Germany, 13353
  • Frankfurt, Germany, 60488
  • Oldenburg, Germany, 26121
  • Bayern
    • Munchen, Bayern, Germany, 80336
• Hungary
  • Budapest, Hungary, H-1121
  • Miskolc, Hungary, H-3529
  • Tatabanya, Hungary, H-2800
• Spain
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28046
  • Madrid, Spain, 28007
  • Malaga, Spain, 29010
  • Zaragoza, Spain, 50009
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
  • California
    • Los Angeles, California, United States, 90033
    • Santa Rosa, California, United States, 95403
  • Florida
    • Tampa, Florida, United States, 33612
  • Illinois
    • Chicago, Illinois, United States, 60611
  • Indiana
    • Lafayette, Indiana, United States, 47905
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02114
    • Danvers, Massachusetts, United States, 01923
  • New York
    • Bronx, New York, United States, 10461
    • New York, New York, United States, 10016
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
    • Pittsburgh, Pennsylvania, United States, 15224
  • Tennessee
    • Nashville, Tennessee, United States, 37232
    • Nashville, Tennessee, United States, 37203
  • Virginia
    • Fairfax, Virginia, United States, 22031
  • Washington
    • Seattle, Washington, United States, 98101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Elevation Oncology
• Collaborators: Merrimack Pharmaceuticals
• Investigators: Study Director: MM-121 Program Medical Director, MD, Merrimack Pharmaceuticals

Publications and helpful links

General Publications

• Sequist LV, Gray JE, Harb WA, Lopez-Chavez A, Doebele RC, Modiano MR, Jackman DM, Baggstrom MQ, Atmaca A, Felip E, Provencio M, Cobo M, Adiwijaya B, Kuesters G, Kamoun WS, Andreas K, Pipas JM, Santillana S, Cho BC, Park K, Shepherd FA. Randomized Phase II Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer. Oncologist. 2019 Aug;24(8):1095-1102. doi: 10.1634/theoncologist.2018-0695. Epub 2019 Apr 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): January 2, 2019
• Study Completion (Actual): January 2, 2019

Study Registration Dates

• First Submitted: February 12, 2015
• First Submitted That Met QC Criteria: March 6, 2015
• First Posted (Estimate): March 12, 2015

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; docetaxel; ErbB3; heregulin
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: MM-121-01-02-09