This is a Phase 1b/2, open-label multicenter study evaluating NKTR-255 as a monotherapy and together with cetuximab in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal carcinoma (CRC).

NKTR-255 is a cytokine that is designed to regulate T and natural killer cell activation, proliferation and promote their anti-tumor effects.

In the dose escalation (Phase 1/b) phase patients with HNSCC or CRC will be treated with ascending doses of NKTR-255 in combination with cetuximab, until the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) is reached.

Key Inclusion Criteria:

• Histologically confirmed diagnosis of a locally advanced or metastatic HNSCC or CRC.
• 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.

HNSCC:

• Progression on any first or second line platinum-based chemotherapy and/or anti-PD-1 or programmed death-ligand 1 antibody.

CRC:

• Patients must have received or were intolerant to at least 2 prior cancer therapy regimens administered for metastatic disease.

Key Exclusion Criteria:

• Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s)
• Prior surgery or radiotherapy within 14 days of initiating study drug(s)
• Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis; active infection requiring systemic therapy within 7 days prior to dosing
• Patients who have been previously treated with IL-2 or IL-15
• Known Grade 3 or 4 hypersensitivity reaction to cetuximab, history of allergy to red meat or tick bites, or history of positive test results for immunoglobulin E antibodies against cetuximab
• Patients who have an active, known, or suspected autoimmune disease

NOTE: Other protocol defined inclusion/exclusion criteria may apply

Only 23 participants were dosed with NKTR-255 (7 in Level 1, 7 in Level 2, 6 in Level 3, 3 in Level 4) and are included in the Safety Population analysis used for the remainder of results data.

Through study completion, up to 6 months.

Adverse events were collected through regular investigator assessments and regular laboratory testing.