A Study of NKTR-262 in Combination With Bempegaldesleukin (NKTR-214) and With Bempegaldesleukin Plus Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumor Malignancies

ID#: NCT03435640

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1/Phase 2

Recruitment Status: Recruiting

Start Date: March 15, 2018

End Date: December 01, 2022

Contact Information:
Nektar Recruitment
855-482-8676
Mona Vimal
855-482-8676
Summary: Patients will receive intra-tumoral (IT) NKTR-262 in 3-week treatment cycles. During the Phase 1 dose escalation portion of the trial, NKTR-262 will be combined with systemic administration of bempegaldesleukin. After determination of the recommended Phase 2 dose (RP2D) of NKTR-262, between 6 and 18 patients may be enrolled at the RP2D to further characterize the safety and tolerability profile of the combination of NKTR 262 plus bempegaldesleukin (doublet) or NKTR 262 plus bempegaldesleukin in combination with nivolumab (triplet) in Cohorts A and B, respectively. In the Phase 2 dose expansion portion, patients will be treated with doublet or triplet in the relapsed/refractory setting and earlier lines of therapy.
Eligibility: Key

Inclusion Criteria:

- Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) metastatic cancer of the following histologies: melanoma (MEL), Merkel cell carcinoma (MCC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), colorectal cancer, head and neck squamous cell carcinoma (HNSCC), or sarcoma.

- 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 enrolled in Cohorts 1-10, Cohort A, Cohort B and Phase 2 Doublet must be refractory to all therapies known to confer clinical benefit to their disease.

- Fresh tumor tissue available for cellular characterization and programmed cell death protein 1 (PD-L1) status.

- Injected lesions (up to two) must be between 20 mm and 90 mm in diameter for IT injection; lesions must be accessible for baseline and on-treatment biopsies. Any liver lesion targeted for injection must not exceed 50 mm at the time of injection.

- Demonstrated adequate organ function within 14 days of Cycle 1 Day 1 (C1D1). Key

Exclusion Criteria:

- Use of an investigational agent or an investigational device within 21 days before administration of first dose of study drug(s).

- Patients treated with prior interleukin-2 (IL-2).

- Patients who have been previously treated with a toll-like receptor (TLR) agonist (excluding topical agents) and patients who have received experimental cancer vaccines.

- Patients who have received systemic interferon (IFN)α within the previous 6 months prior to enrollment to the study.

- Other active malignancy, except non-melanomic skin cancer

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

- Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation-related toxicities, not required corticosteroids and have not had radiation pneumonitis.

- Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening. History of unstable or deteriorating cardiac disease within the previous 6 months prior to screening including but not limited to the following:

- Unstable angina or myocardial infarction.

- Congestive heart failure (NYHA Class III or IV).

- Uncontrolled clinically significant arrhythmias.

- Patients with a history of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration).

- Uveal melanoma will be excluded

- Patients with tumor that invade the superior vena cava or other major blood vessels. Additional general and tumor specific inclusion and exclusion criteria will apply.