within 28 days of declaration
statistical plan

Serum concentrations of ABBV-399 conjugate, total antibody and MMAE and relative titers of ABBV-399 ADA will be determined using validated methods at or under the supervision will be tabulated for each subject, and summary statistics will be computed for each sampling time. Additional exploratory PKPD analyses will be performed if useful and appropriate.  
d.
within 28 days of declaration
laboratory plan

AbbVie Deutschland GmbH and Co KG will serve as the central laboratory for performing the ABBV-399 PK analysis in patients who register to S1400K.  
ABBV-399 (Process II) conjugate and total antibody PK specimens will be analyzed by AbbVie Deutschland GmbH and Co KG. AbbVie Deutschland GmbH and Co KG
G D Bioanalysis Sample Receiving Team Annette Hafner, Thomas Heueck Building 12, Room 324 Knollstrasse 50 67061 Ludwigshafen, Germany Phone:  +49 621 589 2911
+9 621 589 2309 Fax:
Email:   gprd_lupet@abbvie.com ABBV-399 MMAE PK specimens will be analyzed by AbbVie Lake County.  
e.
within 28 days of declaration
specimen shipments

For PK collection, sites will process specimens as outlined in S1400K Section 15.3 and will ship specimens to the SWOG Biospecimen Bank - Solid Tissue, Myeloma and Lymphoma Division, Lab \#201.  Prior to shipping, samples are stored at -20°C
or colder until ready for shipment.  At the end of the study, the SWOG Biospecimen Bank will ship the specimens to AbbVie Deutschland GmbH and Co KG.  
  
Instructions for the SWOG Biospecimen Bank 18.3
within 28 days of declaration
frozen plasma and buffy coat

The SWOG Biospecimen Bank will receive frozen plasma and buffy coat at up to 5 time points per patient. Upon receipt, the Bank will accession, barcode, and bank specimens in a -80°C freezer.
within 28 days of declaration
formalin-fixed paraffin-embedded (ffpe) tissue

The SWOG Biospecimen Bank will receive FFPE specimens as either blocks or slides/sections at up to 2 time points per patient. Upon receipt, the Bank will accession, barcode, and bank specimens at ambient temperature. At the end of the study, the Bank will receive notification from the SWOG Statistics and Data Management Center to distribute specimens for testing.  
Tumor Tissue for Immunotherapy Resistance Analysis The SWOG Biospecimen Bank will send FFPE slides from consented patients for immunotherapy resistance analysis.  
The Bank will send 5-10 unstained slides. If an FFPE tissue block was received, then the SWOG Biospecimen Bank will process up to 10 unstained slides (4 micron, charged, unbaked) to send for testing.
within 28 days of declaration
retrospective c-met testing

The SWOG Statistics and Data Management Center will provide the SWOG Biospecimen Bank with the list of specimens.  The Bank will prepare two (4-5 micron) unstained, charged, and unbaked FFPE slides, per patient.  The slides will be shipped to ARUP for staining.  
a.  
Specimens Shipped to ARUP for Staining ARUP Laboratories 500 Chipeta Way Salt Lake City, UT 84108 Phone: (801) 583/2787 x2166 Email: amy.sandoval@aruplab.com Contact Name: Amy Sandoval b.  
Specimens Shipped to Flagship for Scoring Clinical sample testing is done centrally at Flagship Biosciences, Inc. Flagship is CLIA-certified reference laboratory complying with applicable standards. Flagship Biosciences Inc. 7575 W 103rd Ave, Suite 100 Westminster, CO 80021 Phone: 303/325-5894 C.  
Test Results The ARUP and Flagship process will be conducted in approximately 14 calendar days from receiving the specimens from the Bank.  Flagship will send the c-MET IHC report back to SWOG Statistics and Data Management Center (SDMC).
within 28 days of declaration
analysis of c-met expression with

Bank with the list of specimens. The Bank will prepare 2-8 (4-5 micron) unstained, charged, and air-dried FFPE slides per patient from Archival screening tumor tissue. Unstained slides and the pathology report for initial diagnosis, documenting histologic confirmation of non-small cell lung cancer, will be shipped to AbbVie (address in Section 18.9 ).  
  
18.4 New York Heart Association Classification  
| Need for            | Physical Ability                                                                        |             |                     |                   |
|---------------------|-----------------------------------------------------------------------------------------|-------------|---------------------|-------------------|
| Class               | Cardiac Symptoms                                                                        | Limitations | Additional Rest*    | To Work**         |
| l                   | None                                                                                    | None        | None                | Full Time         |
| l                   | Only moderate                                                                           | Slight      | Usually only slight | Usually full time |
| or occasional       |                                                                                         |             |                     |                   |
| =                   | Defined, with less                                                                      | Marked      | Usually moderate    | Usually part time |
| than ordinary       |                                                                                         |             |                     |                   |
| activity            |                                                                                         |             |                     |                   |
| l                   | May be present                                                                          | Extreme     | Marked              | Unable to work    |
| even at rest, & any |                                                                                         |             |                     |                   |
| activity increases  |                                                                                         |             |                     |                   |
| discomfort          |                                                                                         |             |                     |                   |
| *                   | To control or relieve symptoms, as determined by the patient, rather than as advised by |             |                     |                   |
| the physician.      |                                                                                         |             |                     |                   |
| **                  | At accustomed occupation or usual tasks.                                                |             |                     |                   |  
  
18.5 Monitoring Plan For information on Lung-MAP Monitoring Plan, please refer to S1400 Section 18.0.  
18.6 Storage Temperature Excursion Reporting Form 27 For information on ABBV-399 (Process II) storage temperature excursion, please refer to S1400K Section 3.1 and submit this form.  
Form 27 Form Version: 08Apr2015 Please email or fax this form to the appropriate location per information provided below:  
| Location                 | Email Address            | Fax     |
|--------------------------|--------------------------|---------|
| gdsmtempex.us@abbvie.com | +1 847 785 8101          |         |
| US                       | +49 621 589 68960        |         |
| Germany                  | gdsmtempex.de@abbvie.com |         |
| Number of pages:         | Faxed                    | Emailed |  
Site Staff:
Temperature excursions should be reported to AbbVie within 24 hours after becoming aware of
.  
excursion   and prior to dosing Please notify the Principal Investigator to suspend dispensing affected product. AbbVie will
.  
contact you  regarding acceptability of the investigational product.  
| Protocol Number:                                         | Site Number, if applicable:                        |                                            |         |          |
|----------------------------------------------------------|----------------------------------------------------|--------------------------------------------|---------|----------|
| Principal Investigator:                                  | Country:                                           |                                            |         |          |
| Site Phone Number:                                       |                                                    |                                            |         |          |
| Site Fax Number:                                         |                                                    |                                            |         |          |
| Contact Name:                                            |                                                    |                                            |         |          |
| Lot Number(s):                                           |                                                    |                                            |         |          |
| Kit Number(s):                                           |                                                    |                                            |         |          |
| (Alternatively, attach list of                           |                                                    |                                            |         |          |
| affected kit numbers.)                                   | Excursion Details (Complete All Text Fields Below) |                                            |         |          |
| Duration of Excursion:                                   | hours                                              |                                            |         |          |
| Temperature recorded:                                    | highest:                                           | °Celsius                                   | Lowest: | °Celsius |
| Start Date of Excursion (DD-MMM-YYY):                    |                                                    |                                            |         |          |
| End Date of Excursion (DD-MMM-YYYY):                     |                                                    |                                            |         |          |
| Has any of the affected product been dispensed following | No                                                 | Yes - if so, specify kit number dispensed. |         |          |
| the temperature excursion?                               |                                                    |                                            |         |          |
| Please specify date resupply is needed (DD-MMM-YYYY):    |                                                    |                                            |         |          |
| Reason for Temperature Excursion:                        | appropriate Storage - specify for 'other':         |                                            |         |          |
| Additional Information: (Optional)                       |                                                    |                                            |         |          |
| Reporter Printed Name:                                   |                                                    |                                            |         |          |  
Signature:
Date (DD-MMM-YYYY):  
  
| For AbbVie Internal Use Only: Temperature Excursion Assessment                                               |               |       |
|--------------------------------------------------------------------------------------------------------------|---------------|-------|
| Investigational Product is acceptable.                                                                       |               |       |
| Investigational Product is not acceptable. Investigational Product should be returned/destroyed according to |               |       |
| instructions provided by AbbVie.                                                                             |               |       |
| Comments:                                                                                                    |               |       |
| Printed Name :                                                                                               | Signature:    | Date: |
| (DD-MMM-YYYY)                                                                                                |               |       |
| QA                                                                                                           | QA Signature: | Date: |
| Printed Name :                                                                                               | (DD-MMM-YYYY) |       |
within 28 days of declaration
product complaint form details regarding

| Study Number:                 |
|-------------------------------|
| Investigator/Site information |
| Name:                         |  
| Address:   |
|------------|  
| Country:   |
|------------|  
| 3   |
|-----|  
| 6   |
|-----|  
| (if YES, complete questions 10-14; if NO, proceed to question 15).     |                                                                                  |
|------------------------------------------------------------------------|----------------------------------------------------------------------------------|
| 10                                                                     | Dose administered (i.e. quantity, volume ):                                      |
| Units of dose administered:                                            |                                                                                  |
| ll                                                                     |                                                                                  |
| 12                                                                     | Who administered the medication?                                                 |
| - Investigator - Study Nurse - Patient - Other:                        |                                                                                  |
| Was the administration performed per protocol? (if NO, please explain) |                                                                                  |
| 13                                                                     | Was the subject/caregiver trained? (if NO, please specify)                       |
| 14                                                                     | Were there administration problems prior to this event? (if YES, please specify) |
| 15                                                                     | Did interruption of study medication occur? (if YES, please specify)             |
| 16                                                                     | Page 1 of 2                                                                      |  
| □ Yes   |
|---------|
| □ Yes   |
| □ No    |
| □ Yes   |
| - Yes   |  
  
18.7 Q-03-07-004-F04 Version 2.0 Please fill out this Product Complaint Form and send it to the following email address: RD_PQC_QA@abbvie.com GENERAL INFORMATION
Is an emergency resupply required?  
If yes, please inform your AbbVie monitor or CRA immediately.  
Investigator/Site information Describe complaint: (Provide a detailed description of the complaint including what the subject was doing when the This information is confidential to AbbVie. The user is responsible for using the appropriate version of this document.  
Site Number/RIC Number:
Site Awareness Date l 2 Date complaint reported to AbbViet Date of occurrence/onset (When did this happen):
complaint occurred)
4 Product Name:
5 Serial/lot number of drug product or medical device: Kit number of drug product or medical device:
7
(List all if more than one)
8 Subject Number:
Was the dose administered?  
] No 9.  
(if YES, complete questions 10-14; if NO, proceed to question 15).  
□ Yes Q-03-07-004-F04 Version 2.0
within 28 days of declaration
product complaint form

| Details regarding the staff member reporting the complaint to enable AbbVie to follow-up and   |                                                                                                                            |       |
|------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|-------|
| information gathering regarding complaint                                                      |                                                                                                                            |       |
| 17                                                                                             | Role: - Physician - Nurse - Pharmacy - Hospital/institution - Coordinator - Other:                                         |       |
| 18                                                                                             | Name:                                                                                                                      |       |
| 19                                                                                             | Site address:                                                                                                              |       |
| Work email address:                                                                            |                                                                                                                            |       |
| 2                                                                                              |                                                                                                                            |       |
| 21                                                                                             | Work phone number:                                                                                                         |       |
| Details regarding the complaint                                                                |                                                                                                                            |       |
| Were any tests done to verify condition? (if YES, specify)                                     | No                                                                                                                         |       |
| ,22                                                                                            | - Yes                                                                                                                      |       |
| Is the complaint drug product/medical device available and quarantined? (if NO,                |                                                                                                                            |       |
| explain)                                                                                       | - Yes                                                                                                                      |       |
| 23                                                                                             | - No                                                                                                                       |       |
| 24                                                                                             | Can representative pictures be provided?                                                                                   | I Yes |
| 25                                                                                             | How many units with suspected issue? (i.e. 1 bottle, 10 tablets, 1 pump, 1 tube, etc.):                                    |       |
| Was medication shipment damaged? If YES, provide Clinical Supplies Shipping                    |                                                                                                                            |       |
| Request (CSSR).                                                                                | - Yes                                                                                                                      |       |
| 26.26                                                                                          |                                                                                                                            |       |
| 27                                                                                             | Was the tamper evident seal of the kit intact when it arrived at the site?                                                 | ] No  |
| ] Yes                                                                                          |                                                                                                                            |       |
| Did the site personnel or subject notice any other unusual attributes with the                 |                                                                                                                            |       |
| kit/bottle/packaging? (if YES, specify)                                                        | - Yes                                                                                                                      |       |
| 28                                                                                             | Any additional comments regarding the complaint that are considered relevant and were not collected in any of the sections |       |
| above?                                                                                         |                                                                                                                            |       |
| 29                                                                                             | Was this complaint associated with an adverse event?                                                                       |       |
| 30                                                                                             | No                                                                                                                         |       |
| If YES, adverse event serial number:                                                           | ] Yes                                                                                                                      |       |  
  
This information is confidential to AbbVie. The user is responsible for using the appropriate version of this document.  
18.8 PATIENT DRUG INFORMATION HANDOUT AND WALLET CARD
within 28 days of declaration
information for patients their caregivers

Interactions with Other Drugs and Herbal Supplements is enrolled on a clinical trial using the experimental study The patient drug, ABBV-399 (Process II).  This clinical trial is sponsored by SWOG.  This form is addressed to the patient, but includes important information for others who care for this patient.
within 28 days of declaration
these are the things that

ABBV-399 (Process II) interacts with certain enzymes in the liver and certain transport proteins that help move drugs in and out of cells.  
- The enzyme in question is CYP3A4. ABBV-399 (Process II) is broken down by this enzyme and may be affected by other drugs that strongly inhibit or induce this enzyme.  
- The transport protein in question is P-gp.  ABBV-399 (Process II) is moved in and out of cells/organs by P-gp transporter protein and may be affected by inhibitors or inducers of P-gp.
within 28 days of declaration
to the patient take this

ABBV-399 (Process II) may interact with other drugs which can cause side effects. For this reason, it is very important to tell your study doctors of any medicines you are taking before you enroll onto this clinical trial.  It is also very important to tell your doctors if you stop taking any regular medicines, or if you start taking a new medicine while you take part in this study.  When you talk about your current medications with your doctors, include medicine you buy without a prescription (over-the-counter remedy), or any herbal supplements such as St. John's Wort.  It is helpful to bring your medication bottles or an updated medication list with you.  
Many health care providers can write prescriptions.  You must tell all your health care providers (doctors, physician assistants, nurse practitioners, pharmacists) you are taking part in a clinical trial.
within 28 days of declaration
these are the things that

ABBV-399 (Process II) must be used very carefully with other medicines that use certain liver enzymes and transport proteins to be effective or to be cleared from your system.  Before you enroll onto the clinical trial, your study doctor will work with your regular health care providers to review any medicines and herbal supplements that are considered "strong inducers/inhibitors of CYP 3A4, and transport proteins P-gp."  These characteristics may change how ABBV-399 (Process II) or other medicine works in your body.  
  
- Be very careful!  Over-the-counter drugs (including herbal supplements) may contain ingredients that could interact with your study drug.  Speak to your doctors or pharmacist to determine if there could be any side effects.  
- Avoid ingesting grapefruit juice, grapefruit and Seville oranges while taking ABBV-399 (Process II). - Avoid using herbal medicines or herbal tea. - Your regular health care provider should check a frequently updated medical reference or call your study doctor before prescribing any new medicine or discontinuing any medicine.  Your study doctor's name is
__
and he or she can be contacted at  
  
STUDY DRUG INFORMATION WALLET CARD
You are enrolled on a clinical trial using the experimental study drug ABBV-399 (Process II). This clinical trial is sponsored by SWOG.  
ABBV-399 (Process II) may interact with drugs that are processed by your liver, or use certain transport proteins in your body.  Because of this, it is very important to:
. Tell your doctors if you stop taking any medicines or if you start taking any new medicines.  
1 Tell all your health care providers (doctors, physician assistants, nurse practitioners, or pharmacists) that you are taking part in a clinical trial.  
. Check with your doctor or pharmacist whenever you need to use an over-the-counter medicine or herbal supplement.  
1 Avoid ingesting grapefruit, grapefruit juice and Seville oranges and avoid herbal tea/medicines while on trial.  
▷ ABBV-399 (Process II) may interact with CYP 3A4 and transport protein P-gp, and must be used very carefully with other medicines that interact with this enzyme and transport protein.  
. Before you enroll onto the clinical trial, your study doctor will work with your regular health care providers to review any medicines and herbal supplements that are considered "strong inducers/inhibitors of CYP 3A4 and transport protein P-gp."
7 Before prescribing new medicines, your regular health care providers should go to a frequently-updated medical reference for a list of drugs to avoid, or contact your study doctor.  
➤ Your study doctor's name is _  
| and can be contacted at _   |
|-----------------------------|  
  
Analysis of c-MET Expression with Response to ABBV-399 (Process II)
within 28 days of declaration
a. objective

To evaluate the association between c-MET expression (RNA and protein) with investigator-assessed progression-free survival (IA-PFS) in patients with c-MET Immunohistochemistry (IHC) positive previously-treated stage IV or recurrent squamous cell lung cancer treated with ABBV-399.  
To evaluate the association between c-MET expression (RNA and protein) with overall survival (OS) in this study population.  
The analyses will not include an assessment of association with response as only 2 patients in the study had a response.  
b.
within 28 days of declaration
background

ABBV-399 (Process II) is a first-in-class antibody-drug conjugate (ADC) which is comprised of ABT-700, an anti-c-MET monoclonal antibody, linked to monomethyl auristatin E (MMAE), a potent microtubule inhibitor, hence delivering direct antimitotic effect without relying on MET pathway inhibition. Preliminary data show that ABBV-399 (Process II) monotherapy is well tolerated, preliminary efficacy data from Phase I study (M14-237) with 41 patients with c-MET+ NSCLC (7 Squamous, 34 non-squamous) receiving either  ≥1.6 mg/kg Teliso-V Q2W (n=19) and ≥2.4 mg/kg  Teliso-V  Q3W  (n=22)  showed  objective  response  (partial/complete response) in 22% patients with median progression-free survival, 5.2 months.  
Squamous lung cancer is a disease where there is a dire need for effective targeted therapies. ABBV-399 (Process II) has a potential to improve the quality of life and outcome of patients with squamous cell lung cancer, based on its tolerability and preliminary efficacy. Translational medicine studies will help identify additional predictive markers and would help identify a patient population that would benefit most from ABBV-399 (Process II).  Efforts will be made to establish correlation between response and expression levels of c-MET or other genes RNA
levels in the screening tissue. This will help in future development of appropriate CDx.  
C
within 28 days of declaration
eligibility

The tissue for this analysis must be S1400K Squamous NSCLC tumor tissue
(archival or fresh pre-dose biopsy) that is c-MET positive.  
d.
within 28 days of declaration
assay description

AbbVie scientists have extensive experience with genomic and proteomic based platforms.  It is anticipated that AbbEie will receive remaining tumor tissue (at least 2 unstained slides) from screening tumor tissue (from primary tumor or metastatic lesion) for translational medicine research.  Briefly, tumor genomic material will be extracted using the QIAGEN AllPrep Kit (QIAGEN Sciences, Germantown, MD,
USA). RNAseq library preparation will be prepared using the SeqPlex RNA Amplification Kit (Sigma-Aldrich, St. Louis, MO, USA) per manufacturer's protocol and sequenced on Illumina Novaseq using pair end reads extending 100 bases.  
e.
within 28 days of declaration
statistical plan

18.9 A Cox Proportional Hazards model will be used to evaluate the association between c-MET expression (RNA and protein) and time-to-event outcomes (IA- PFS and OS).  Kaplan-Meier curves will be used to display distributions by c-MET
expression level groups (evaluating subgroups by quantiles or medians).  Medians will be estimated in subgroups and associated confidence intervals using the method of Brookmeyer - Crowley.  
Once these analyses have been completed by the SWOG SDMC and the data are provided to AbbVie, the information learned from biomarker analysis may be used to investigate factors influencing response to treatment or scientific questions related to Squamous NSCLC solid tumor and/or in the development of diagnostic tests. The results of biomarkers will be qualitative. The data will be combined with the biomarker data collected in M14-237 (first in human study to evaluate Teliso-
V activity) to understand the Teliso-V activity in NSCLC subjects.  
f.
within 28 days of declaration
laboratory plan

Personalis, Inc. will be contracted by AbbVie to analyze the tumor tissue for RNAseq.  
Tissue will be shipped to:
AbbVie Marion Refici 1 North Waukegan Road AP10 Rm 114 North Chicago, IL 60064 Phone: 262-308-2562 Email:   Marion.Refici@abbvie.com g.
within 28 days of declaration
specimen requirements

For screening tumor tissue, sites have processed specimens as outlined in S1400 Section 15.2.  The tissue was collected before ABBV-399 (Process II) dosing on S1400K. The Bank will prepare 2-8 FFPE unstained slides (4-5 micron thick) from screening tumor tissue (archival or fresh biopsy) per patient and send the pathology report for initial diagnosis, documenting histologic confirmation of nonsmall cell lung cancer. The Bank will ship samples at ambient temperature to the address listed above to be routed to the appropriate lab for analysis.  
Any remaining tissue at the completion of analysis must be shipped back the SWOG Biospecimen Bank - Solid Tissue, Myeloma and Lymphoma Division, Lab
\#201 and not used for further testing. Leftover tissue will remain at the SWOG Biospecimen Bank for future exploratory analysis.