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

Non-Small Cell Lung Cancer Clinical Trial

— 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.)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02387216
• Other study ID #: MM-121-01-02-09
• Status: Terminated
• Phase: Phase 2
• Start date: February 1, 2015
• Est. completion date: January 2, 2019

Study information

• Verified date: October 2021
• Source: Elevation Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 153
• Est. completion date: January 2, 2019
• Est. primary completion date: January 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Non-Small-Cell Lung
• Heregulin
• Lung Neoplasms
• Non-Small Cell Lung Cancer
• NSCLC

Intervention

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

Locations

Country	Name	City	State
France	CHI Creteil	Créteil	Paris
France	Centre Léon Bérard	Lyon cedex 08	Rhône-Alpes

Sponsors (2)

Lead Sponsor	Collaborator
Elevation Oncology	Merrimack Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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