Brief Title: Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally Advanced or Metastatic Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®)

Primary Outcome 1 - Timeframe: 100 days after last dose

Primary Outcome 2 - Measure: Recommended Phase 2 Dose (RP2D) or Maximum Tolerated Dose (MTD) or optimal dosing schedule of NKTR-214 in combination with pembrolizumab (Keytruda®)

Primary Outcome 2 - Timeframe: 100 days after last dose

Primary Outcome 3 - Measure: Objective response rate (ORR) per blinded independent central review (BICR) by RECIST 1.1 of NKTR-214 plus pembrolizumab with or without systemic chemotherapy in patients with untreated metastatic NSCLC

Primary Outcome 3 - Timeframe: 100 days after last dose

CONDITION

• Non-Small Cell Lung Cancer
• Melanoma
• Urothelial Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Hepatocellular Carcinoma

ELIGIBILITY

Inclusion Criteria:
Dose Optimization and Dose Expansion Inclusion Criteria:
Willing and able to provide written informed consent.

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

- Life expectancy > 12 weeks from the time of enrollment as determined by the Investigator.

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

- Oxygen saturation ≥ 92% on room air for all indications.

- Measurable disease per RECIST 1.1.

- Patients with brain metastases are eligible if certain criteria are met.

- Availability of fresh or archival tumor tissue

- Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment
Dose Optimization Inclusion Criteria (Multiple Solid Tumors):
Melanoma:
Histologically confirmed stage IV (metastatic) melanoma.
Non-small Cell Lung Cancer:
Histologically confirmed diagnosis of stage IV NSCLC

- Must not have received systemic anti-PD-L1 therapy for metastatic disease.

- Patients with actionable mutations with approved targeted therapy in NSCLC are excluded. Testing for mutations should be performed in accordance with standard of care.
Urothelial Carcinoma:
Histologically confirmed diagnosis of metastatic urothelial carcinoma
Head and Neck Squamous Cell Carcinoma (HNSCC)
Histologically confirmed diagnosis of metastatic HNSCC
Hepatocellular Carcinoma (HCC)
Histologically confirmed diagnosis of metastatic HCC
Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer):
Histologically confirmed diagnosis of stage IV NSCLC.

- Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment.

- Patients with actionable mutations with approved targeted therapy in NSCLC are excluded. Testing for mutations should be performed per standard of care.

- Must not have received anti-cancer therapy for treatment of metastatic lung cancer

- Must not have received prior immunotherapy
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 an active autoimmune disease

- History of allergy or hypersensitivity to study drug components

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

- Prior surgery or radiotherapy within 14 days of therapy.

- For Dose Optimization Cohort 1 only: Chemotherapy or biological therapy within 28 days of enrollment. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of enrollment. Patients with ongoing AEs related to prior cancer therapies will be excluded.

- Participant's inability to adhere to or tolerate protocol or study procedures
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Study Director

Role: Study Director

Affiliation: Nektar Therapeutics

Overall Contact

Name: Study Director

Phone: 855-482-8676

Email: StudyInquiry@nektar.com, medicalaffairs@nektar.com

LOCATION