History of Changes for Study: NCT02983045

A Dose Escalation and Cohort Expansion Study of CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 Antibody (Nivolumab) in Patients With Select Advanced or Metastatic Solid Tumors (PIVOT-02)

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Study Record Versions

Version	Submitted Date	Changes
1	December 1, 2016	None (earliest Version on record)
2	January 9, 2017	Contacts/Locations and Study Status
3	March 3, 2017	Outcome Measures, Study Status, Arms and Interventions, Contacts/Locations, Eligibility, Study Design, Study Description and Study Identification
4	May 2, 2017	Study Status and Contacts/Locations
5	September 5, 2017	Study Status and Contacts/Locations
6	November 6, 2017	Contacts/Locations, Arms and Interventions, Study Description, Oversight, Study Status, Eligibility, Study Design, Conditions and Sponsor/Collaborators
7	February 26, 2018	Contacts/Locations, Arms and Interventions, Study Description, Study Status, Eligibility, Outcome Measures and Study Design
8	May 22, 2018	Study Status, Arms and Interventions, Study Design, Contacts/Locations, Outcome Measures, Study Description, Study Identification and Eligibility
9	October 18, 2018	Contacts/Locations, Outcome Measures, Study Description, Study Status, Eligibility and Arms and Interventions
10	October 31, 2019	Contacts/Locations, Outcome Measures, Arms and Interventions, Study Status, Conditions, Study Description, Study Identification, Eligibility, Study Design and Oversight
11	May 29, 2020	Recruitment Status, Study Status, Contacts/Locations, Arms and Interventions, Study Design and Study Description
12	January 3, 2021	Study Status
13	May 20, 2021	Study Status and Study Identification
14	July 13, 2021	Study Status and Contacts/Locations
15	July 28, 2021	Contacts/Locations and Study Status
16	August 24, 2021	Study Status
17	September 28, 2021	Study Status
18	October 5, 2021	Study Status
19	November 30, 2021	Study Status
20	April 27, 2022	Arms and Interventions, Study Status, Outcome Measures, Conditions, Study Description and Study Design
21	June 22, 2022	Recruitment Status, Study Status
	Results Submission Events
November 29, 2022 February 13, 2023		Returned after QC review: December 28, 2022 Returned after QC review: March 9, 2023
22	March 9, 2023	Arms and Interventions, Study Status, Outcome Measures, Study Description, Document Section, Results and IPDSharing

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	16-214-02
Brief Title:	A Dose Escalation and Cohort Expansion Study of CD122-Biased Cytokine (NKTR-214) in Combination With Anti-PD-1 Antibody (Nivolumab) in Patients With Select Advanced or Metastatic Solid Tumors (PIVOT-02)
Official Title:	A Phase 1/2, Open-Label, Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of CD122-Biased Cytokine (NKTR-214) and Anti-PD-1 Antibody (Nivolumab) in Patients With Select Locally Advanced or Metastatic Solid Tumor Malignancies.
Secondary IDs:

Study Status


Record Verification:	December 2016
Overall Status:	Recruiting
Study Start:	October 2016
Primary Completion:	October 2017 [Anticipated]
Study Completion:	October 2018 [Anticipated]

First Submitted:	November 23, 2016
First Submitted that Met QC Criteria:	December 1, 2016
First Posted:	December 6, 2016 [Estimate]

Last Update Submitted that Met QC Criteria:	December 1, 2016
Last Update Posted:	December 6, 2016 [Estimate]

Sponsor/Collaborators


Sponsor:	Nektar Therapeutics
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	No

Study Description

Brief Summary:

This study is to determine first, the recommended Phase 2 dose of NKTR-214 when administered in combination with nivolumab, and then, the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab in select patients with melanoma, renal cell carcinoma or non-small cell lung cancer. Both drugs target the immune system and may act synergistically to promote anti-cancer effects.

Detailed Description:

NKTR-214 is a cytokine (investigational agent) that is designed to target CD122, a protein which is found on certain immune cells (known as CD8+ T Cells and Natural Killer Cells) to expand these cells to promote their anti-tumor effects. Nivolumab is a full human monoclonal antibody that binds to a molecule called PD-1 on immune cells and promotes anti-tumor effects.

Approximately 30 eligible patients that enroll in the dose escalation portion of the study (Phase 1) will be assigned to one of three dose regimens of NKTR-214 (0.006 mg/kg every 21 days, 0.003 mg/kg every 14 days, or 0.006 mg/kg every 14 days) in combination with 240 mg of nivolumab every 14 days. Based on safety, tolerability and efficacy observed in the trial, enrollment to additional dose escalation cohorts are planned. The first phase of the study will test the safety and efficacy profile of the combination and determine which dose will be studied in Phase 2 of the overall study. During Phase 2, cohorts of patients with specific cancers will be expanded and these patients will receive the recommended Phase 2 dose and schedule of NKTR-214 (as determined by Phase 1) in combination with 240 mg of nivolumab every 14 days.

All patients enrolled in the study will be closely monitored to determine if there is response to the treatment as well as for any side effects that may occur. The efficacy of the combination will be assessed using objective response rate (ORR). Immunological biomarkers in plasma and tumor samples will evaluate immune activation.

Conditions


Conditions:	Carcinoma，Non-Small-Cell Lung Carcinoma, Renal Cell Melanoma
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1/Phase 2
Interventional Study Model:	Single Group Assignment
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	30 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

Experimental: Combination of NKTR-214 + nivolumab

NKTR-214 in escalating doses, will be combined with an approved dose of nivolumab per label indication. The goal of this dose escalation part of the study is to find the recommended phase 2 dose.

For the second part of the study, enrollment into a dose expansion cohort will commence once the Recommended Phase 2 Dose (RP2D) is established for this combination.

Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects.

Drug: Combination of NKTR-214 + nivolumab

Phase 1: Patients with select tumor types will receive NKTR-214 doses administered either every 21 days or every 14 days in combination with 240 mg nivolumab (Opdivo®) every 14 days.

Phase 2: Additional patient cohorts with select tumor types will be dosed at the recommended Phase 2 dose/schedule of NKTR-214 (as determined by Phase 1 of the trial) in combination with 240 mg nivolumab every 14 days.

Other Names:

NKTR-214 + Opdivo®

Outcome Measures


Primary Outcome Measures:
1.	Safety of NKTR-214 in combination with nivolumab as evaluated by incidence of drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), and adverse events leading to discontinuation, deaths, and clinical laboratory test abnormalities [ Time Frame: 30 days after last dose ]
2.	Tolerability of NKTR-214 in combination with nivolumab as evaluated by incidence of Dose Limiting Toxicities (DLTs), drug-related AEs, SAEs, adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: 30 days after last dose ]
Secondary Outcome Measures:
1.	Objective Response Rate (ORR) of NKTR-214 with nivolumab based on RECIST 1.1 [ Time Frame: Through study completion, an expected average of 2 years ] ORR will be measured and defined three ways: the percentage of patients achieving a confirmed complete or partial response, as defined by RECIST 1.1; the percentage of patients achieving a confirmed complete or partial response, as defined by immune-related RECIST 1.1; and the percentage of patients achieving a confirmed complete or partial response, as defined by immune-related response criteria (irRC)
2.	Best Overall Response (BOR) in the population of interest [ Time Frame: Through study completion, an expected average of 2 years ]
3.	Duration Of Response (DOR) [ Time Frame: Through study completion, an expected average of 2 years ] It is defined as time between the date of first radio-graphic images that documented objective response and the date of the radio-graphic images that documented disease progression.
4.	Progression-Free Survival (PFS) [ Time Frame: Through study completion, an expected average of 2 years ] PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause
5.	Clinical Benefit Rate (CBR) [ Time Frame: Through study completion, an expected average of 2 years ] Clinical benefit rate will be assessed as the number of subjects with confirmed Complete Response (CR), confirmed Partial Response (PR), or Stable Disease (SD) (where the duration of SD should be ≥ 84 days) divided by the total number of subjects in the Response Evaluable Population
6.	Median Time to Response (MTR) [ Time Frame: Through study completion, an expected average of 2 years ] The median time to response will be summarized descriptively for subjects who have a CR or PR
7.	Overall Survival (OS) [ Time Frame: Within 3 years from study start ] Overall survival is defined as the time from date of first dose to the date of death
8.	Maximum observed plasma concentration (Cmax) of NKTR-214 [ Time Frame: Cycle 1 and 2 Day 1: 0.25 hr., 1.5 hr, 3 hr., 6 hr., Days 2, 3, 4, 5, 8, 11, and 15. Cycles ≥ 3 Day 1: 0.25 hour on Day 8 ]
9.	Time of maximum observed plasma concentration (Tmax) of NKTR-214 [ Time Frame: Cycle 1 and 2 Day 1: 0.25 hr., 1.5 hr, 3 hr., 6 hr., Days 2, 3, 4, 5, 8, 11, and 15. Cycles ≥ 3 Day 1: 0.25 hour on Day 8 ]
10.	Area under the plasma concentration time curve in the dosing interval Area Under the Curve (AUC) of NKTR-214 [ Time Frame: Cycle 1 and 2 Day 1: 0.25 hr., 1.5 hr,, 3hr., 6 hr., Days 2, 3, 4, 5, 8, 11, and 15 for cycle 1 and 2. Cycles ≥ 3 Day 1: 0.25 hour on Day 8 ]
11.	Half-life (t½) of NKTR-214 [ Time Frame: Cycle 1 and 2 Day 1: 0.25 hr., 1.5 hr., 3hr., 6 hr. Days 2, 3, 4, 5, 8, 11, and 15 for cycle 1 and 2. Cycles ≥ 3 Day 1: 0.25 hour on Day 8 ]
12.	Changes in blood immune cells by flow cytometry [ Time Frame: Day 1 and Day 8 of Cycle 1 and 2 ]
13.	Changes in soluble cytokines and chemokines by multiplexed ELISA [ Time Frame: Day 1 and Day 8 of Cycle 1 and 2 ]
14.	Functional and phenotypic characterization of tumor immune infiltrates by flow cytometry [ Time Frame: Pre-dose and week 3 after first dose ]
15.	Functional and phenotypic characterization of tumor immune infiltrates by next generation sequencing [ Time Frame: Pre-dose and week 3 after first dose ]
16.	Functional and phenotypic characterization of tumor immune infiltrates by immunohistochemistry (IHC) [ Time Frame: Pre-dose and week 3 after first dose ]

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Patients with RCC or NSCLC must have received only 1 prior line of therapy and must not have received prior immunotherapy with specified immunomodulators. Patients with melanoma must be treatment naïve Histologically confirmed diagnosis of a locally advanced or metastatic melanoma, renal cell carcinoma (RCC), or non-small cell lung cancer (NSCLC) Life expectancy >12 weeks Patients must not have received prior interleukin 2 (IL 2) therapy Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 Measurable disease per RECIST 1.1 Demonstrated adequate organ function within 14 days of treatment initiation Oxygen saturation ≥ 92% on room air. NSCLC patients may use supplemental oxygen 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 for at least 3 months after the last dose of study drugs Patients with stable brain metastases may be enrolled if certain criteria are met Sample of archival tumor tissue and fresh baseline tumor biopsies are required 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 History of organ transplant that requires use of immune suppressive agents Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis Prior surgery or radiotherapy within 14 days of therapy Participants who have had < 28 days since the last chemotherapy, 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

Contacts/Locations


Central Contact Person:	Nektar Recruitment Telephone: 855-482-8676 Email: StudyInquiry@nektar.com
Study Officials:	Michael Imperiale, MD Study Director Nektar Therapeutics
Locations:	United States, Connecticut
	Local Institution - New Haven [Not yet recruiting] New Haven, Connecticut, United States, 06473
	United States, New York
	Local Institution - Buffalo [Not yet recruiting] Buffalo, New York, United States, 14263
	Local Institution - New York [Not yet recruiting] New York, New York, United States, 10016
	United States, Oregon
	Local Institution - Portland [Recruiting] Portland, Oregon, United States, 97213
	United States, Texas
	Local Institution - Houston [Recruiting] Houston, Texas, United States, 77030
	United States, Washington
	Local Institution - Seattle [Not yet recruiting] Seattle, Washington, United States, 98109

IPDSharing


Plan to Share IPD:	Undecided

References


Links:
Available IPD/Information: