Study of NKTR 255 in Combination With Cetuximab in Solid Tumors

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), colorectal carcinoma (CRC), cutaneous squamous cell carcinoma (cSCC), anal cell carcinoma (ASCC) and cervical cancer. The recommended phase 2 dose of NKTR-255, determined in the dose escalation phase (Phase 1b), will be used to treat patients in Phase 2 of this study.

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. The recommended phase 2 dose of NKTR-255 will be used to treat patients in Phase 2 of this study.

In the dose expansion phase (Phase 2), patients will be treated with NKTR-255 alone and together with cetuximab as follows: Cohort A - HNSCC; Cohort B - CRC; Cohort C - cSCC; Cohort D - ASCC; Cohort E - Cervical Cancer.

Patients who achieve optimal response will be given the option to continue treatment with NKTR-255 as single agent for maintenance.

Eligibility Criteria:
Key Inclusion Criteria:

* Histologically confirmed diagnosis of a locally advanced or metastatic HNSCC, CRC, cSCC, ASCC, or cervical cancer.
* 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.

cSCC

* Patients must have received prior therapy including anti-PD-1 and platinum-based chemotherapy, have documented platinum-refractory disease, or be ineligible/unfit for platinum-based therapy.

aSCC

* Patients must have received prior therapy including anti-PD-1 and platinum-based chemotherapy, have documented platinum-refractory disease, or be ineligible/unfit for platinum-based therapy.
* If human immunodeficiency virus (HIV)-positive, patients must also have CD4+ count ≥ 300/μL, undetectable viral load, and be receiving highly active antiretroviral therapy at the time of screening.

Cervical Cancer

* Patients must have experienced progression (or toxicity precluding additional treatment) on any first- or second-line platinum-based chemotherapy and anti-PD-(L)1, have documented platinum-refractory disease, or be ineligible/unfit for platinum-based therapy.
* Patients must have known status by pathology for HPV

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