A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR-214 in adult patients with locally advanced or metastatic solid tumors.

Official Title
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An Open-Label, Multicenter, Dose Escalation And Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumor Malignancies

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: NKTR-214


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor. Received 1 or 2 prior lines of therapy. Life expectancy >12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. Measurable disease per RECIST v1.1. Demonstrated adequate organ function within 14 days of treatment initiation. Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior system anticancer therapy, radiotherapy or surgery. Women of childbearing potential must agree to use highly effective methods of birth control. All participants must agree to use double barrier contraception during study participation and for at least 2 months after the last dose of study drug. Additional criteria may apply. Exclusion Criteria: Use of an investigational agent or an investigational device within 28 days before administration of first dose of NKTR-214. Females who are pregnant or breastfeeding. Participants who have an active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. Active central nervous system (CNS) metastases. Prior surgery or radiotherapy within 14 days of therapy. Participants who have had < 28 days since the last chemotherapy, immunotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone or equivalent before administration of the first dose of study medication. Participants' inability to adhere to or tolerate protocol or study procedures. Additional criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKTR-214 Dose Escalation<br>This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR--214 in adult patients with locally advanced and metastatic solid tumors. The Phase 1 stage of the study is designed as an open-label dose escalation trial of NKTR--214 in participants with locally advanced or metastatic solid tumors. The goal of the dose escalation stage of the study is to find the recommended phase 2 dose, to evaluate the efficacy of NKTR--214 by assessing the objective response rate and to evaluate the safety of NKTR-214. Immunological biomarkers in plasma and tumor samples will also be measured. | Drug: NKTR-214<br>* Participants in the dose escalation cohorts will be treated every 21 days (q21d) or every 14 days (q14d) until tumor progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of NKTR-214 as Evaluated by Incidence of Drug-related Adverse Events (AEs) | This outcome quantifies the number and types of adverse events associated with NKTR-214. | 30 days after last dose, approximately 533 days | 
| Tolerability of NKTR-214 as Evaluated by Incidence of Dose Limiting Toxicities (DLTs) | The data below reflects the incidence of Dose Limiting Toxicity Events observed in this trial. | 30 days after last dose, up to 533 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Solid Tumors, Locally Advanced Solid Tumors