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

• ClinicalTrials.gov Identifier: NCT02387216
• Recruitment Status: Terminated
• First Posted: March 12, 2015
• Results First Posted: October 12, 2021
• Last Update Posted: October 12, 2021
• Sponsor: Elevation Oncology
• Collaborator: Merrimack Pharmaceuticals
• Information provided by (Responsible Party): Elevation Oncology

Tracking Information

• First Submitted Date: February 12, 2015
• First Posted Date: March 12, 2015
• Results First Submitted Date: September 22, 2020
• Results First Posted Date: October 12, 2021
• Last Update Posted Date: October 12, 2021
• Actual Study Start Date: February 1, 2015
• Actual Primary Completion Date: January 2, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2021)

Progression Free Survival [ Time Frame: Randomization 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.

Original Primary Outcome Measures (submitted: March 6, 2015)

Progression-free survival [ Time Frame: Time from randomization to progression, approximately 2 years ]

Disease status will be assessed according to RECIST v 1.1

Current Secondary Outcome Measures (submitted: October 11, 2021)

• Overall Survival [ Time Frame: From 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 Rate [ Time Frame: Randomization 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
• Time to Progression [ Time Frame: Randomization 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 Alone [ Time Frame: TEAEs 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. [ 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 ]
  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 [ Time Frame: TEAEs 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

Original Secondary Outcome Measures (submitted: March 6, 2015)

• Overall Survival [ Time Frame: Time from randomization to death, approximately 2 years ]
• Objective Response Rate [ Time Frame: Approximately 2 years ]
• Rate of adverse events reported with the combination of MM-121 with docetaxel or pemetrexed [ Time Frame: Approximately 2 years ]
• Pharmacokinetic (PK) parameters of MM-121 in combination with docetaxel or pemetrexed, specifically focusing on "Area under the plasma concentration versus time curve (AUC)". [ Time Frame: Approximately 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of MM-121 in Combination With Chemotherapy Versus Chemotherapy Alone in Heregulin Positive NSCLC
• 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.)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer
• NSCLC
• Adenocarcinoma
• Heregulin

Intervention

• Drug: MM-121
  Investigational, fully human antibody targeting and inhibiting ErbB3
  Other Name: seribantumab
• Drug: Docetaxel
  approved chemotherapy treatment for NSCLC
  Other Name: Taxotere

Study Arms

• Experimental: Arm A: Experimental Arm
  MM-121 in combination with Docetaxel
  Interventions:

  • Drug: MM-121
  • Drug: Docetaxel
• Active Comparator: Arm B: Comparator Arm
  Docetaxel alone
  Intervention: Drug: Docetaxel

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 5, 2019): 153
• Original Estimated Enrollment (submitted: March 6, 2015): 120
• Actual Study Completion Date: January 2, 2019
• Actual Primary Completion Date: January 2, 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Germany, Hungary, Spain, United States

Administrative Information

• NCT Number: NCT02387216
• Other Study ID Numbers: MM-121-01-02-09
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Elevation Oncology
• Original Responsible Party: Merrimack Pharmaceuticals
• Current Study Sponsor: Elevation Oncology
• Original Study Sponsor: Merrimack Pharmaceuticals
• Collaborators: Merrimack Pharmaceuticals

Investigators

• Study Director: MM-121 Program Medical Director, MD; Merrimack Pharmaceuticals

• PRS Account: Elevation Oncology
• Verification Date: October 2021