A Study of a CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 (Pembrolizumab) and of NKTR-214 in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Select Advanced or Metastatic Solid Tumors

NKTR-214 is a cytokine (investigational agent) that is designed to target CD122, a protein
which is found on certain immune cells (known as CD8+ T Cells and Natural Killer Cells) to
expand these cells to promote their anti-tumor effects. Pembrolizumab is a programmed death
receptor -1 (PD-1) blocking antibody and atezolizumab is a fully humanized, engineered
monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1
(PD-L1) that promotes anti-tumor effects.

The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214
with pembrolizumab or atezolizumab and will enroll approximately 75 patients into two
separate arms concurrently. The first arm will evaluate an every three-week dose regimen
(q3w) of NKTR-214 in combination with pembrolizumab in up to 46 patients in approved
treatment settings of pembrolizumab, including patients with melanoma or non-small cell lung
cancer. The second arm will evaluate a q3w dose regimen of NKTR-214 in combination with
atezolizumab in up to 29 patients in approved treatment settings of atezolizumab, including
patients with urothelial carcinoma. The NKTR-214 dose to be studied is 0.006 mg/kg q3w based
on the safety observed in the monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295)
and an ongoing combination trial (16-214-02, NCT02983045). The dose of pembrolizumab or
atezolizumab to be studied will be that in their approved labelling.

For NKTR-214 + Pembrolizumab, eligible patients include:

- Melanoma: 1st line; PD-L1 Status- all

- NSCLC: 1st line; PD-L1 Status ≥ 50%

For NKTR-214 + Atezolizumab, eligible patients include:

- Urothelial carcinoma: 1st line; PD-L1 Status - all

- Disease progression within 12 months of neoadjuvant or adjuvant treatment with
chemotherapy

- Urothelial carcinoma: 2nd line; PD-L1 Status - all

- Disease progression during or following platinum-containing chemotherapy.

Inclusion Criteria:

- Willing and able to provide written informed consent.

- Histologically confirmed locally advanced melanoma (pembrolizumab only), metastatic
NSCLC (pembrolizumab only) locally advanced or metastatic urothelial carcinoma
(atezolimumab only).

- Male or female patients, age 18 years or older at the time of signing the informed
consent form (ICF).

- Life expectancy > 12 weeks as determined by the Investigator.

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

- Measurable disease per RECIST 1.1.

- Patients must not have received prior immuno-oncology regimens, including but not
limited to inhibitors such as anti PD-1, anti-PD-L1, anti-PD-L2, anti CD137, or anti
CTLA-4 (cytotoxic T lymphocyte-associated protein 4) antibody, or any other antibody
or drug specifically targeting T cell co stimulation or checkpoint pathways,
indoleamine 2,3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell
therapies, or other cytokine therapies.

- Additional criteria may apply.

MELANOMA (pembrolizumab only)

- Histologically confirmed stage III (unresectable) or stage IV melanoma, as per
American Joint Committee on Cancer (AJCC) staging system

- Uveal melanoma is excluded

- Have not received prior anti-cancer therapy for advanced or metastatic melanoma

- Patients with unknown BRAF mutation status may enroll so long as mutation testing is
planned to be performed within 30 days of Cycle 1 Day 1

First-line NSCLC (pembrolizumab only)

- Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC

- Patients must have high PD-L1 expression (Tumor Proportion Score [TPS] ≥ 50%) as
determined by FDA-approved test, with no epidermal growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

First- or Second-line UROTHELIAL CARCINOMA (atezolizumab only)

- Histologically or cytologically documented locally advanced or metastatic urothelial
carcinoma

- First-line patients who have disease progression within 12 months of neoadjuvant or
adjuvant treatment with chemotherapy.

- Second-line patients who have disease progression during or following
platinum-containing chemotherapy.

Exclusion Criteria:

- Use of an investigational agent or an investigational device within 28 days before
administration of first dose of study drug(s).

- Females who are pregnant or breastfeeding.

▪ Patients who have active or stable brain metastases or who have a history of brain
metastases.

- Patients who have an active, known or suspected autoimmune disease. Patients requiring
systemic treatment within the past 3 months or a documented history of clinically
severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
(Exceptions include any patient on 10 mg or less of prednisone or equivalent, patients
with vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves'
disease, Hashimoto's disease, alopecia areata, eczema, or with Medical Monitor
approval).

- History of allergy or hypersensitivity to study drug components. Prior malignancy
treated with anticancer therapy (including systemic chemotherapy, radiation and/or
surgery) within the previous 3 years except for locally curable cancers that have been
apparently cured, such as basal or squamous cell skin cancer, superficial bladder
cancer, or carcinoma in situ of the prostate, cervix, or breast.• History of organ
transplant that requires use of immune suppressive agents.

- Evidence of clinically significant interstitial lung disease or active, noninfectious
pneumonitis.

- Prior surgery or radiotherapy within 14 days of initiating therapy. Patients must have
recovered from all radiation-related toxicities, and not required corticosteroids.

- Additional criteria may apply