SHERLOC: A Phase 2 Study of MM-121 in Combination with Chemotherapy versus Chemotherapy Alone in Patients with Heregulin Positive Non-Small Cell Lung Cancer.
- Conditions
- Heregulin Positive, Locally Advanced or Metastatic Non-Small Cell Lung CancerMedDRA version: 20.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003673-42-DE
- Lead Sponsor
- Merrimack Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 135
To be eligible for participation in the study, patients must meet the following criteria. Patients who are assessed to be HRG negative do not complete any screening procedures beyond HRG assessment.
• Patients with cytologically or histologically documented NSCLC classified as adenocarcinoma that is presenting as either:
o Stage IV (metastatic disease) or
o Stage IIIB or IIIC disease not amenable to surgery with curative intent or
o Recurrent or progressive disease following multimodal therapy (chemotherapy, radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced or metastatic disease)
• Disease progression or evidence of recurrent disease during or after the last systemic therapy as documented by radiographic assessment
• Received one prior platinum-based regimen for management of primary or recurrent disease
• Received nivolumab, pembrolizumab, or other anti-PD-1 or anti-PD-L1 therapy, where available and clinically indicated
• Clinically eligible for treatment with docetaxel once every three weeks per the investigator's judgment
• Must have at least one lesion amenable to collection of tissue
• A positive in-situ hybridization (ISH) test for heregulin with a score of =1+, as determined by centralized testing
• ECOG performance status (PS) of 0 or 1
• Screening ECG without clinically significant abnormalities
• Women of childbearing potential, as well as fertile men and their partners, must be willing to abstain from sexual intercourse or to use an effective form of contraception (an effective form of contraception is an oral contraceptive or a double barrier method or as defined by country specific guidelines) during the study and for 6 months, in males and
females, following the last dose of study drug(s), or greater, as in accordance with the label requirements or institutional guidelines for docetaxel
• = 18 years of age
• Able to provide informed consent, or have a legal representative able and willing to do so
• Patients who have experienced a venous thromboembolic event within 60 days of signing the main consent form should have been treated with anti-coagulants for at least 7 days prior to beginning treatment and for
the duration of treatment on this study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27
To be eligible for randomization, patients must not meet any of the following criteria:
• Known Anaplastic Lymphoma Kinase (ALK) gene rearrangement
• Presence of exon 19 deletion or exon 21 (L858R) substitution of the EGFR gene
• Pregnant or lactating
• Prior radiation therapy to >25% of bone marrow-bearing areas
• Received >2 prior lines of systemic anti-cancer drug regimens for locally advanced and/or metastatic disease
o Any type of maintenance therapy, e.g. pemetrexed maintenance following first line treatment with cisplatin and pemetrexed, is not considered a separate line of therapy
• Prior treatment with an anti-ErbB3 antibody
• Prior treatment with docetaxel for advanced/ metastatic disease
• Received other recent antitumor therapy including:
o Investigational therapy administered within the 28 days or 5 half-lives, whichever is shorter, prior to the first scheduled day of dosing in this study
o Radiation or other standard systemic therapy within 14 days prior to the first scheduled dose in this study, including, in addition (if necessary), the timeframe for resolution of any actual or anticipated toxicities from such radiation
• CTCAE grade 3 or higher peripheral neuropathy
• Presence of an unexplained fever > 38.5°C during screening visits that does not resolve prior to the first day of dosing. If the fever and active infection have resolved prior to randomization, the patient will be eligible. At the discretion of the investigator, patients with tumor fever may be enrolled.
• Clinically active CNS metastasis
• Use of strong CYP3A4 inhibitors
• Any other active malignancy requiring systemic therapy
• Known hypersensitivity to any of the components of MM-121 or previous CTCAE grade 3 or higher hypersensitivity reactions to fully human monoclonal antibodies
• History of severe hypersensitivity reactions to docetaxel
• Known hypersensitivity to polysorbate (Tween) 80 or arginine
• Inadequate bone marrow reserve as evidenced by:
o ANC < 1,500/µl or
o Platelet count < 100,000/µl or
o Hemoglobin < 9 g/dL (5.59 mmol/L)
• Serum/plasma creatinine > 1.5 x ULN
• Inadequate hepatic function as evidenced by:
o Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 x ULN concomitant with Alkaline phosphatase (AP) > 2.5 x ULN
o Serum/plasma total bilirubin > ULN
• Clinically significant cardiac disease, including: symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 12 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; or active human immunodeficiency virus (HIV) infection, active hepatitis B infection or active hepatitis C infection
• Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method