Pegzilarginase and Pembrolizumab for Extensive Disease Small Cell Lung Cancer

Key Inclusion Criteria:

1. Patient is able and willing to provide written informed consent

2. Be > 18 years of age on day of signing informed consent

3. Have histologically or cytologically confirmed SCLC that meets:

1. Extensive disease per criteria of the International Association for the Study of
Lung Cancer (IASLC)-American Joint Committee on Cancer (AJCC) TNM staging system

2. Have not tolerated or have progressed or relapsed on or within 6 months of
platinum-based chemotherapy

4. Have a performance status of ≤ 1 on the ECOG Performance Scale

5. Have measurable disease based on RECIST 1.1

6. Willing to undergo core needle or incisional biopsy to obtain fresh tumor tissue
specimens

7. Demonstrate adequate organ function as evidenced by laboratory testing with specimens
collected within 10 days prior to day 1 of cycle 1

8. Female child-bearing potential must have a negative urine or serum pregnancy test
within 72 hours prior to receiving the first dose of study medication

9. Sexually active male or female must be surgically sterile post-menopausal, or must
agree to use a physician-approved method of birth control during the study through a
minimum of 120 days after the last study drug administration.

Key Exclusion Criteria:

1. Has received more than 2 platinum-based regimens against SCLC

2. Has received pembrolizumab, or prior therapy with an anti-PD-1, anti-PD-L1,
anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as
part of any previous therapy, including trials

3. Has participated in Merck MK-3475 (pembrolizumab) clinical trials

4. Has received pegzilarginase as part of any previous therapy

5. Is currently participating in a study of an investigational agent or received the last
dose of an investigational agent within 4 weeks prior to the first dose of treatment
in this study (a shorter interval for kinase inhibitors or other short half-life drugs
could be considered after approval from the Sponsor). Is currently participating in a
study of an investigational device within 4 weeks of the first dose of treatment

6. Has a diagnosis of an immunodeficiency, is receiving systemic steroid therapy (except
for physiological dose levels), or immunosuppressive therapies

7. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous
cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical
cancer) that has undergone potentially curative therapy

8. Has known central nervous system (CNS) metastases. However, patients with previously
treated brain metastases may participate provided neurologic symptoms have stabilized,
there is no evidence of new brain metastases or hemorrhage and they are not using
steroids for brain metastases or for complications derived from their treatment for at
least 7 days prior to the first dose of trial treatment

9. Has known carcinomatous meningitis

10. Has an active autoimmune disease requiring systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs) or a documented history of clinically severe autoimmune disease, or a syndrome
that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or
resolved childhood asthma/atopy are an exception to this rule. Patients that require
intermittent use of bronchodilators or local steroid injections will not be excluded
from the study. Patients with hypothyroidism stable on hormone replacement or
Sjorgen's syndrome will not be excluded from the study. Replacement therapy (e.g.
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, etc) is not considered a form of systemic treatment

11. Has evidence of interstitial lung disease, history of non-infectious pneumonitis that
required steroids, or current pneumonitis

12. Inadequately controlled hypertension (defined as systolic blood pressure ≥ 200 mmHg
and/or diastolic blood pressure ≥ 120 mmHg) on more than one occasion in the month
before planned day of infusion

13. Currently taking 3 or more anti-hypertensive medications

14. Prior history of hypertensive crisis or hypertensive encephalopathy

15. History of myocardial infarction, unstable angina, cardiac or other vascular stenting,
angioplasty, or cardiac or vascular surgery within 6 months prior to day 1 of study
treatment

16. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment

17. Has a known history of Human Immunodeficiency Virus (HIV) (positive for HIV p24
antigen or HIV 1/2 antibodies)

18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected)

19. Has a known history of active tuberculosis (Bacillus tuberculosis)

20. Has had an allogenic tissue/solid organ transplant.