Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors

Patients with metastatic or recurrent solid malignancy who have progressed on first line
standard of care treatment or for which defined standard of care does not exist or is not
readily available are eligible to participate on this trial. Patients for which pembrolizumab
has an FDA approved indication and for whom pembrolizumab is covered by their insurance
should receive standard commercial pembrolizumab and will not be eligible for this trial.

The primary objective of this trial is to evaluate the Immune-Related Objective Response Rate
(IR-ORR) achieved with pembrolizumab in patients with Fanconi Anemia Repair Pathway
functionally competent and functionally deficient tumors.

Trial treatment should be administered on Day 1 of each cycle after all
procedures/assessments have been completed. Trial treatment may be administered up to 3 days
before or after the scheduled Day 1 of each cycle due to administrative reasons.

All trial treatments will be administered on an outpatient basis.

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Target
infusion timing is 30 minutes.

Expansion Cohort:

Ten (10) additional subjects with the diagnosis of metastatic or recurrent endometrial
carcinoma will be enrolled in the trial at the conclusion of regular enrollment.

Inclusion Criteria:

- Have measurable disease based on RECIST 1.1.

- Be willing to provide consent for retrieval of archival tumor material tissue from a
previously obtained core or excisional biopsy of a tumor lesion.

- Have a tumor presentation at screening for which pembrolizumab does not have an FDA
approved indication for commercial use.

- Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.

- Demonstrate adequate organ function

- Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication.

Expansion cohort - additional criteria

1. Diagnosis of Endometrial Carcinoma or Sarcoma which is metastatic and has failed
standard treatment or is recurrent, or for which standard chemotherapy is
contraindicated or refused by patient.

2. Sufficient tissue is available for correlative studies

3. MSI studies have been performed, either by immunohistochemistry or next generation
sequencing and results show that patient is MS low or stable.

Exclusion Criteria:

- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy, or used an investigational
device within 4 weeks of the first dose of treatment.

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment.

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.

- Has a known history of active Bacillus Tuberculosis

- Hypersensitivity to pembrolizumab or any of its excipients.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable. This exception does not include carcinomatous meningitis which is
excluded regardless of clinical stability.

- Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs).

- Has immunohistochemically proven mismatch repair deficient cancer

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis

- Evidence of interstitial lung disease.

- Has an active infection requiring systemic therapy.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

- 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.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

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

- Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.