Lung-MAP S1400K: c-MET Positive

Study Overview
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Brief Summary
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S1400K of Lung-MAP seeks to evaluate the overall response rate with ABBV-399 (Process II) in patients with c-MET positive SCCA. S1400K is a biomarker-driven study for patients with Stage IV or recurrent squamous cell lung cancer, who have c-MET positive squamous cell tumors.

Official Title
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A Phase II Study of ABBV-399 in Patients With C-Met Positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP SUB-STUDY)

Conditions
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Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma AJCC V7

Intervention / Treatment
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* Drug: ABBV-399


Participation Criteria
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Eligibility Criteria
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•Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: A BIOMARKER-DRIVEN MASTER PROTOCOL FOR PREVIOUSLY TREATED SQUAMOUS CELL LUNG CANCER 5.1 Sub-Study Specific Disease Related Criteria Patients must have been assigned to S1400I. Patients must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways. Patients must not have an active, known, or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. 5.2 Sub-Study Specific Clinical/Laboratory Criteria Patients must not have any known allergy or reaction to any component of the nivolumab and ipilimumab formulations. Patients must not have received systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to sub-study registration. Inhaled or topical steroids, and adrenal replacement doses <= 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease. Patients must not have a known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Patients with a positive hepatitis C antibody with a negative viral load are allowed. [This criterion replaces common eligibility criteria in Section 5.3m.] Patients must not have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). [This criterion replaces common eligibility criteria in Section 5.3n.] Patients must not have interstitial lung disease that is symptomatic or disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity. Patients must also be offered participation in banking for future use of specimens as described in Section 15.0. Patients must have a Lipase, Amylase, TSH with reflex Free T3/T4 performed within 7 days prior to sub-study registration. Additional timepoints are noted in Section 9.0, Study Calendar. [Note: For the Canadian sites, testing for lipase only is acceptable.] Patients must not have any Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia (see Section 18.1b). Patients with a history of congestive heart failure (CHF) or at risk because of underlying cardiovascular disease or exposure to cardiotoxic drug should have an EKG and echocardiogram performed to evaluate cardiac function as clinically indicated. Patients with evidence of congestive heart failure (CHF), myocardial infarction (MI), cardiomyopathy, or myositis should have a cardiac evaluation including lab tests and cardiology consultations as clinically indicated including EKG, CPK, troponin, and echocardiogram. Patients who can complete PRO forms in English are required to complete a pre-study S1400I Patient Reported Outcomes (PRO) Questionnaire and a pre-study S1400I EQ-5D Questionnaire within 14 days prior to registration (see Section 18.2 of S1400I). NOTE: Patients enrolled to S1400I prior to 9/1/2016 are not eligible for the PRO study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-399<br>C-MET overexpression is seen in 30% of patients with lung squamous cell carcinoma (SCCA). ABBV-399 (Process II) is a first-in-class antibody-drug conjugate (ADC) comprised of ABT-700, an anti-c-Met monoclonal antibody linked to monomethyl auristatin E (MMAE), which is a potent microtubule inhibitor. This delivers a direct anti-mitotic effect without relying on MET pathway inhibition. ABBV-399 will be administered intravenously on day 1 of each 21-day cycle. Treatment will continue in consenting patients until disease progression or intolerable toxicity. | Drug: ABBV-399<br>* ABBV-399 (Process II), 2.7 mg/kg IV over 30 ± 10 minutes, Day 1, Every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate in Participants With c-Met Positive Lung Squamous Cell Carcinoma (SCCA) | The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with ABBV-399 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). | 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed Progression-free Survival) in Immunotherapy-exposed and Relapsed Participants With c-Met Positive Lung Squamous Cell Carcinoma (SCCA). | Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration or death due to any cause. | up to 3 years post sub-study registration | 
| Overall Survival (OS) in Immunotherapy-exposed and Relapsed Participants With c-Met Positive Lung Squamous Cell Carcinoma (SCCA). | Duration from date of sub-study registration (or date of screening/pre-screening registration if patient never enrolls in a sub-study) to date of death due to any cause | up to 3 years post sub-study registration | 
| Overall Response Rate (ORR) in Immunotherapy-exposed and Relapsed Participants With c-Met Positive Lung Squamous Cell Carcinoma (SCCA). | The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with ABBV-399 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). | Up to 3 years | 
| Investigator-assessed Progression-free Survival (IA-PFS) in Participants With c-Met Positive Lung Squamous Cell Carcinoma (SCCA) | Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration or death due to any cause | Up to 3 years post sub-study registration | 
| Overall Survival (OS) in Participants With c-Met Positive Lung Squamous Cell Carcinoma (SCCA) | Duration from date of sub-study registration (or date of screening/pre-screening registration if patient never enrolls in a sub-study) to date of death due to any cause. | Up to 3 years post sub-study registration | 
| Duration of Response (DoR) | Duration from date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause among participants who achieve a complete or partial response. | Up to 3 years post sub-study registration | 
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adverse Events (AEs) are reported by CTCAE Version 5.0 for serious adverse events only and CTCAE Version 4.0 for routine toxicity reporting. Only adverse events that are possibly, probably or definitely related to study drug are reported. | Duration of treatment and follow up until death or 3 years post sub-registration |