Phase 1 Open-label Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab

Inclusion Criteria:

- Advanced Solid Malignancies: Histologically documented metastatic or locally advanced,
incurable solid malignancy (Parts A and B); histologically documented metastatic or
locally advanced, incurable solid malignancy for which gemcitabine is clinically
appropriate (e.g., non-small cell lung, breast, ovarian, pancreatic, and renal
cancer); histologically documented metastatic or locally advanced, incurable solid
malignancy for which pembrolizumab (Part D) or nivolumab (Part E) is approved. NOTE:
Parts D and E only: Subject has either (1) received treatment with pembrolizumab or
nivolumab for ≥4 months with a best response of stable disease and plans to continue
treatment with either pembrolizumab or nivolumab in accordance with package insert; or
(2) is not currently taking, but is eligible for treatment with, pembrolizumab or
nivolumab in accordance with the approved indications for each as referenced in the
package insert.

- Expected survival of at least 12 weeks after dosing.

- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

- Evidence of adequate organ function by standard laboratory tests.

- All female subjects of child bearing age must be either surgically sterile,
postmenopausal for at least 1 year, or using an acceptable method of contraception.
Adequate contraception for both male and female subjects must be used from the
beginning of the screening period until at least 8 weeks after the last dose of study
drug.

Exclusion Criteria:

- Hematologic malignancies or multiple myeloma.

- Known, clinically important cardiac or respiratory disease

- Any concomitant serious physical illness other than cancer (e.g., immune deficiency
disease, bleeding disorder, etc.) within 1 year prior to dosing. No history of
autoimmune disease.

- Active, uncontrolled infections within 7 days of study entry requiring systemic
therapy.

- Evidence of progression of central nervous system (CNS) metastases or symptomatic CNS
metastases within 30 days prior to dosing.

- History of known or suspected autoimmune disease with the specific exceptions of
vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment. (Parts C,
D and E only).

- Clinically-significant gastrointestinal disorders, such as perforation,
gastrointestinal bleeding, or diverticulitis (Parts D and E only).

- Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
systemic treatment (Parts D and E only).

- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
(Parts D and E only).

- History of interstitial lung disease (Parts D and E only).