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

Primary Purpose

Non-Small Cell Lung Cancer, NSCLC, Adenocarcinoma

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MM-121
Docetaxel
Sponsored by
Elevation Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring NSCLC, Non-Small Cell Lung Cancer, heregulin, ErbB3, docetaxel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHI Creteil
  • Centre Léon Bérard

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A: Experimental Arm

Arm B: Comparator Arm

Arm Description

MM-121 in combination with Docetaxel

Docetaxel alone

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
February 12, 2015
Last Updated
October 11, 2021
Sponsor
Elevation Oncology
Collaborators
Merrimack Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02387216
Brief Title
A Study of MM-121 in Combination With Chemotherapy Versus Chemotherapy Alone in Heregulin Positive NSCLC
Acronym
SHERLOC
Official Title
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.)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Based on the preliminary results seen during interim analysis, which were confirmed in the final analysis, the Sponsor terminated the study
Study Start Date
February 1, 2015 (Actual)
Primary Completion Date
January 2, 2019 (Actual)
Study Completion Date
January 2, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Elevation Oncology
Collaborators
Merrimack Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, NSCLC, Adenocarcinoma, Heregulin
Keywords
NSCLC, Non-Small Cell Lung Cancer, heregulin, ErbB3, docetaxel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
Randomized
Enrollment
153 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Experimental Arm
Arm Type
Experimental
Arm Description
MM-121 in combination with Docetaxel
Arm Title
Arm B: Comparator Arm
Arm Type
Active Comparator
Arm Description
Docetaxel alone
Intervention Type
Drug
Intervention Name(s)
MM-121
Other Intervention Name(s)
seribantumab
Intervention Description
Investigational, fully human antibody targeting and inhibiting ErbB3
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
approved chemotherapy treatment for NSCLC
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
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.
Time Frame
Randomization until progression of disease or death due to any cause within 3 years,11 months (the study terminated prematurely)
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause
Time Frame
From date of randomization until the date of death from any cause assessed upto 3 years,11 months (the study terminated prematurely)
Title
Objective Response Rate
Description
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
Time Frame
Randomization through end of study up to 3 years, 11 months (the study terminated prematurely)
Title
Time to Progression
Description
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.
Time Frame
Randomization to date of objective tumor progression up to 3 years, 11 months (the study terminated prematurely)
Title
Number of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone
Description
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
Time Frame
TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months
Title
Pharmacokinetic (PK) Parameters of MM-121 in Combination With Docetaxel and Docetaxel When Given in Combination With MM-121.
Description
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.
Time Frame
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
Title
Percentage of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone
Description
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
Time Frame
TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MM-121 Program Medical Director, MD
Organizational Affiliation
Merrimack Pharmaceuticals
Official's Role
Study Director
Facility Information:
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Danvers
State/Province
Massachusetts
ZIP/Postal Code
01923
Country
United States
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
CHI Creteil
City
Créteil
State/Province
Paris
ZIP/Postal Code
94010
Country
France
Facility Name
Centre Léon Bérard
City
Lyon cedex 08
State/Province
Rhône-Alpes
ZIP/Postal Code
69317
Country
France
City
Munchen
State/Province
Bayern
ZIP/Postal Code
80336
Country
Germany
City
Bad Berka
ZIP/Postal Code
99437
Country
Germany
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Frankfurt
ZIP/Postal Code
60488
Country
Germany
City
Oldenburg
ZIP/Postal Code
26121
Country
Germany
City
Budapest
ZIP/Postal Code
H-1121
Country
Hungary
City
Miskolc
ZIP/Postal Code
H-3529
Country
Hungary
City
Tatabanya
ZIP/Postal Code
H-2800
Country
Hungary
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Malaga
ZIP/Postal Code
29010
Country
Spain
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
30975923
Citation
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.
Results Reference
derived

Learn more about this trial

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

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