Lung-MAP: Rilotumumab and Erlotinib Hydrochloride or Erlotinib Hydrochloride Alone as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches

PRIMARY OBJECTIVES:

I. To evaluate if there is sufficient evidence to continue to the phase III component of
S1400E by comparing investigator-assessed progression-free survival (IA-PFS) between
rilotumumab plus erlotinib versus erlotinib in patients registered to S1400E. (Phase II) II.
To determine if there is both a statistically and clinically-meaningful difference in IA-PFS
between patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase
III) III. To compare overall survival (OS) in patients randomized to rilotumumab plus
erlotinib versus erlotinib. (Phase III)

SECONDARY OBJECTIVES:

I. To compare response rates (confirmed and unconfirmed, complete and partial responses)
among patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase II)
II. To evaluate the frequency and severity of toxicities associated with rilotumumab plus
erlotinib versus erlotinib. (Phase II) III. To compare the response rates (confirmed and
unconfirmed, complete and partial) among patients randomized to receive rilotumumab plus
erlotinib versus erlotinib. (Phase III) IV. To evaluate the frequency and severity of
toxicities associated with rilotumumab plus erlotinib versus erlotinib. (Phase III)

TERTIARY OBJECTIVES:

I. To evaluate the treatment arm randomization acceptance rate within each treatment arm of
S1400E defined as the percentage of patients randomized to a treatment arm that receive any
protocol treatment.

II. To identify additional predictive or prognostic tumor/blood biomarkers beyond the chosen
biomarker.

III. To identify potential resistance biomarkers at disease progression. IV. To establish a
tissue/blood repository from patients with refractory squamous cell cancer.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I (CLOSED TO ACCRUAL AND INTERVENTION11/25/2014): Patients receive rilotumumab
intravenously (IV) over 60-120 minutes on day 1 and erlotinib hydrochloride orally (PO) daily
on days 1-21. Courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL AND INTERVENTION11/25/2014): Patients receive erlotinib
hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, all patients will be followed until death or 3 years
after sub-study registration, whichever occurs first.

Inclusion Criteria:

- Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON
ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master
Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)

- Patients must be assigned to S1400E; S1400E biomarker eligibility defined as C-MET
positive is defined as follows:

- Analyte: C-MET

- Assay: Immunohistochemistry (IHC)

- Eligible definition: IHC positive based on Dako MET-IHC pharm DX kit

- If randomized to arm I rilotumumab plus erlotinib, patients must be willing to provide
blood specimens for anti-rilotumumab anti-body testing

- Patients must not have peripheral edema > grade 1 at the time of sub-study
registration

- Patients must not have received prior treatment with MET pathway, inhibitors or EGFR
inhibitors (e.g., erlotinib)

- Patients must have total bilirubin =< 1.5 x institutional upper limits of normal
(IULN) within 28 days prior to sub-study registration

- Patients must not have abnormalities of the cornea based on history (e.g., dry eye
syndrome, Sjorgren?s syndrome), congenital abnormality (e.g., Fuch?s dystrophy),
abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose),
and/or abnormal corneal sensitivity test (Schirmer test or similar tear production
test)

- Patients must not be taking, nor plan to take while on protocol treatment and for 14
days post the last dose of study treatment, drugs, herbal supplements or foods that
are known to be strong/moderate CYP3A4 substrates