A PHASE II STUDY OF ABBV-399 (PROCESS II) IN PATIENTS WITH C-MET POSITIVE STAGE IV OR RECURRENT SQUAMOUS CELL LUNG CANCER (LUNG-MAP SUB-STUDY)

(In addition to S1400 Lung-MAP criteria)

5.1 Sub-Study Specific Disease Related Criteria

a. Patients must be assigned to S1400K. The c-Met testing will be performed at a protocol specified central laboratory. S1400K biomarker eligibility defined as C-Met positive squamous cell is as follows:

Analyte Assay Eligible definition
c-Met Immunohistochemistry IHC positive based on Ventana SP44 Assay (H score >= 150)

b. Patients must have pathologically proven squamous cell carcinoma (SCCA) cancer of the lung confirmed by tumor biopsy and/or fine-needle aspiration.

5.2 Sub-Study Specific Clinical/Laboratory Criteria

a. Patients must have received at least on line of a platinum-based chemotherapy regimen and experienced disease progression (in the opinion of the treating physician) on or following this regimen.

b. Patients must not have peripheral edema > Grade 1, or peripheral neuropathy > Grade 1 at the time of sub-study registration.

c. Patients must not have received prior treatment with c-Met pathway inhibitors.

d. Patients must not be taking strong CYP3A4 inhibitors within 7 days prior to sub-study registration, nor plan to take while on protocol treatment and for 14 days after the last dose of study treatment. (see S1400K Section 7.2).

e. Patients must have albumin >= 3.0 g/dL within 28 days prior to sub-study registration.

f. Patients must have adequate hepatic function as defined by serum bilirubin <= Institutional Upper Limit of Normal (IULN) and either ALT or AST <= 2.5 x IULN (if both ALT and AST are done, both must be < 2.5 IULN) and gamma-glutamyl transferase (GGT) <=5 x ULN within 28 days prior to sub-study registration. [This criterion replaces common eligibility criteria in S1400K Section 5.3i]

g. Patients with extensive metastatic liver disease involving >= 50% of the liver in the judgment of the Investigator or sum of longest diameters of RECIST measurable liver lesions >= 10 cm will not be enrolled. [This criterion replaces common eligibility criteria in S1400K Section 5.3i]

h. Patients must not have a history of interstitial lung disease or of pneumonitis that required treatment with systemic steroids.

i. Patients must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. These patients must agree to use contraception while on study treatment and for up to 6 months after the last dose of study treatment/drug. [This criterion replaces common eligibility criteria in S1400K Section 5.3q]

j. Patients must agree to have blood specimens submitted for pharmacokinetic analysis as outlined in S1400K Section 15.3.

k. Patients must also be offered participation in banking for future use of specimens as described in S1400K Section 15.0.

5.3 Common Eligibility Criteria for all Sub-Studies

a. Patients whose biomarker profiling results indicate the presence of an EGFR mutation or EML4/ALK fusion are not eligible. Due to existence of approved therapies the biomarker exclusion rules are per table.

b. Patients must have progressed (in the opinion of the treating physician) following the most recent line of therapy.

c. Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration. Patients must have recovered (<= Grade 1) from any side effects of prior therapy. Patients must not have received any radiation therapy within 14 days prior to sub-study registration. (See S1400K Section 5.3e for criteria regarding therapy for CNS metastases).

d. Patients must have measurable disease (see S1400K Section 10.1) documented by CT or MRI. The CT from a combined PET/CT may be used to document only non-measurable disease unless it is of diagnostic quality as defined in S1400K Section 10.1c. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration. See S1400K Section 15.0 and S1400 Section 18.3 for guidelines and submission instructions for required central radiology review.

e. Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to sub-study registration. Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration.

f. Patients must have fully recovered from the effects of surgery at least 14 days prior to sub-study registration.

g. Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.

h. Patients must have an ANC >= 1,500/mcl, platelet count ≥ 100,000 mcl, and hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study registration.

i. [This common eligibility criteria has been removed as it conflicts with the sub-study specific criteria in S1400K Sections 5.2e and 5.2f. A place holder remains to keep consistency across all sub-studies]

j. Patients must have a serum creatinine ≤ the IULN OR measured OR calculated creatinine clearance >= 50 mL/min using the following Cockroft-Gault Formula:

Calculated Creatinine Clearance = (140 - age) X (actual body weight in kg) †
72 x serum creatinine *

Multiply this number by 0.85 if the patient is a female. This specimen must have been drawn and processed within 28 days prior to sub-study registration.

† The kilogram weight is the patient weight with an upper limit of 140% of the IBW.
* Actual lab serum creatinine value with a minimum of 0.8 mg/dL.

k. Patients must have Zubrod performance status of 0-1 (see S1400K Section 10.4) documented within 28 days prior to sub-study registration.

l. 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 S1400K Section 18.4).

m. Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection.

n. Patients with a known history of HIV seropositivity:

1. Must have undetectable viral load using standard HIV assays in clinical practice.
2. Must have CD4 count >= 400/mcL.
3. Must not require prophylaxis for any opportunistic infections (i.e., fungal, MAC, or PCP prophylaxis).
4. Must not be newly diagnosed within 12 months prior to sub-study registration.

o. Prestudy history and physical exam must be obtained within 28 days prior to sub-study registration.

p. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.

q. [This common eligibility criteria has been removed as it conflicts with the sub-study specific criteria in S1400K Sections 5.2g. A place holder remains to keep consistency across all sub-studies]

r. As a part of the OPEN registration process (see S1400 Section 13.4 for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

s. Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator).

t. Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.