FindTrial
Sign In

A Dose Escalation and Cohort Expansion Study of NKTR-214 in Combination With Nivolumab and Other Anti-Cancer Therapies in Patients With Select Advanced Solid Tumors

A Phase 1/2, Open-label, Multicenter Study of the Combination of NKTR-214 and Nivolumab or the Combination of NKTR-214, Nivolumab, and Other Anti-Cancer Therapies in Patients With Select Locally Advanced or Metastatic Solid Tumor Malignancies

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02983045
Acronym
PIVOT-02
Enrollment
557
Registered
2016-12-06
Start date
2016-12-19
Completion date
2022-04-28
Last updated
2023-03-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastric Cancer, HR+/HER2- Breast Cancer, Melanoma, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Triple Negative Breast Cancer, Urothelial Carcinoma

Keywords

NKTR-214, Bempegaldesleukin, Nivolumab, Paclitaxel, Carboplatin, Cisplatin, Pemetrexed, Melanoma, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Urothelial Carcinoma, Triple Negative Breast Cancer, HR+/HER2- Breast Cancer, Gastric Cancer, Colorectal Cancer, Metastatic, Advanced, Immunotherapy, Anti-PD-1, anti-CTLA-4

Brief summary

In this four-part study, NKTR-214 was administered in combination with nivolumab and with/without other anticancer therapies. Part 1 considered escalating doublet (NKTR 214 + nivolumab) doses to determine the RP2D. Part 2 considered dose expansion cohorts for the doublet (NKTR 214 + nivolumab ± chemotherapy). Part 3 was schedule-finding for a triplet therapy (NKTR 214 + nivolumab + ipilimumab). Part 4 dose expansion for the triplet (NKTR 214 + nivolumab + ipilimumab) was planned to further assess the efficacy of the RP2D triplet combination at dosing schedules from Part 3.

Detailed description

Part 1 enrolled patients with advanced or metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), urothelial carcinoma, or triple negative breast cancer (TNBC) to determine the recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD) of NKTR 214 + nivolumab doublet therapy. Part 2 enrolled patients with advanced or metastatic solid tumor malignancies (including 9 tumor types consisting of the same 5 tumor types as in Part 1, plus hormone receptor positive human epidermal growth factor receptor 2 \[HER 2\] negative breast cancer \[HR+ HER2- BC\], gastric cancer, colorectal carcinoma, and small cell lung cancer \[SCLC\]) to assess the efficacy of the RP2D. Part 3 enrolled patients with advanced or metastatic melanoma, RCC, NSCLC, or urothelial carcinoma (UCC) in a first-line setting (1L) to assess the safety and tolerability of NKTR 214 + nivolumab + ipilimumab triplet therapy Three dosing schedules were evaluated to establish RP2D dosing schedules for Part 4 of the study. Part 4 planned to enroll patients with advanced or metastatic melanoma, RCC, NSCLC, or UCC to further assess the efficacy of the RP2D triplet combination at the 3 dosing schedules from Part 3. Patients were enrolled simultaneously to each tumor cohort. All patients enrolled in the study were closely monitored for safety, tolerability and response per RECIST criteria. The primary efficacy endpoint was objective response rate (ORR) using RECIST 1.1 at the RP2D doublet.

Interventions

DRUGDose Escalation Doublet: Combination of NKTR-214 + nivolumab

NKTR 214 + nivolumab at 5 dosage levels.

DRUGDose Expansion Doublet: Combination of NKTR-214 + nivolumab

Select patient cohorts with select tumor types will be dosed with NKTR-214 + nivolumab at the RP2D + other anti-cancer therapies per institution standard.

DRUGSchedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab

1L patients with RCC, NSCLC, UCC, and melanoma received NKTR-214 0.006 mg/kg q3w in combination with nivolumab and ipilimumab according to 3 dosing schedules.

DRUGDose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab

Combination of NKTR-214 + nivolumab + ipilimumab was administered at RP2D dose/schedules in select tumor types

Sponsors

Bristol-Myers Squibb
CollaboratorINDUSTRY
Nektar Therapeutics
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

- For Parts 1-4: * Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) or metastatic solid tumors * Life expectancy \> 12 weeks * Patients must not have received prior interleukin-2 (IL-2) therapy * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Measurable disease per RECIST 1.1 * Patients with stable brain metastases under certain criteria * Fresh and archival tumor tissue available Tumor specific inclusion criteria may apply.

Exclusion criteria

- For Parts 1-4: * 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 * Active malignancy not related to the current diagnosed malignancy * Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis * Participants who have had \< 28 days since the last chemotherapy, biological therapy, or \< 14 days from approved tyrosine kinase inhibitor (TKI) therapy, or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone Tumor specific

Design outcomes

Primary

MeasureTime frameDescription
Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowIncludes DLTs that occurred within the DLT window of at least 21 days after the first dose of study treatment (28 days for every 2 weeks dosing; 21 days for every 3 weeks dosing). Patients were counted only once under each preferred term.Part 1of the study was a dose-escalation phase that evaluated the safety and tolerability and defined the maximum tolerated dose or recommended Phase 2 dose of the NKTR-214/nivolumab doublet across 5 dosage/schedule levels. The results presented are for the DLT Population.
Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowDose-limiting toxicities (DLTs) were assessed during a 3-week (21-day) DLT evaluation period beginning with the first dose of ipilimumab.Part 3 of the study was a schedule finding phase to establish the recommended phase 2 dosing schedules for Part 4 and assess the safety and tolerability for the NKTR-214/nivolumab/ipilimumab triplet combination. The results presented are for the DLT Population.
Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)Tumor assessment at Screening then every 8 weeks (± 7 days) from Cycle 1 Day 1 and end of treatment (unless scan done within 4 weeks) up to approximately 27 months.Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) at Recommended Phase 2 Dose (RP2D). ORR is defined as the percentage of enrolled participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.

Countries

Belgium, Canada, France, Italy, Poland, Spain, United Kingdom, United States

Participant flow

Participants by arm

ArmCount
Part 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w
NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 240 mg nivolumab q2w.
4
Part 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w
NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.
3
Part 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w
NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.003 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.
3
Part 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w
NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.
25
Part 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w
NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.009 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.
3
Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w
In this Part 2 of the study, the patients will receive a combination of NKTR-214 + nivolumab at the RP2D (NKTR 214 0.006 mg/kg q3w + nivolumab 360 mg q3w) with or without chemotherapy.
476
Part 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab
In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 1, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 360 mg flat dose q3w + ipilimumab at 1 mg/kg q6w.
10
Part 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab
In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 2, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 1 mg/kg q3w + ipilimumab at 3 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.
8
Part 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab
In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 3, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 3 mg/kg q3w + ipilimumab at 1 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.
6
Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab
Experimental Combination of NKTR-214 + nivolumab ipilimumab that may enroll between 12-26 patients per tumor type Combination of NKTR-214 + nivolumab: Combination of NKTR-214 + nivolumab +ipilimumab administered at the RP2D dose/schedule.
19
Total557

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007FG008FG009
Overall StudyLost to Follow-up00000100000
Overall StudyWithdrawal by Subject01050720002

Baseline characteristics

CharacteristicTotalPart 4 Dose Expansion of NKTR-214 + Nivolumab + IpilimumabPart 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + IpilimumabPart 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + IpilimumabPart 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + IpilimumabPart 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w
Age, Continuous61.7 years
STANDARD_DEVIATION 11.32
59.1 years
STANDARD_DEVIATION 12.63
61.2 years
STANDARD_DEVIATION 9.3
64.3 years
STANDARD_DEVIATION 5.85
62.4 years
STANDARD_DEVIATION 9.45
62.1 years
STANDARD_DEVIATION 11.48
55.7 years
STANDARD_DEVIATION 6.81
59.2 years
STANDARD_DEVIATION 10.12
57.0 years
STANDARD_DEVIATION 7.81
61.7 years
STANDARD_DEVIATION 7.37
54.8 years
STANDARD_DEVIATION 10.9
ECOG Performance Status
0
276 Participants12 Participants5 Participants6 Participants6 Participants221 Participants3 Participants16 Participants2 Participants2 Participants3 Participants
ECOG Performance Status
1
280 Participants7 Participants1 Participants2 Participants4 Participants254 Participants0 Participants9 Participants1 Participants1 Participants1 Participants
ECOG Performance Status
Data Missing
1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
46 Participants2 Participants2 Participants2 Participants1 Participants35 Participants2 Participants0 Participants2 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
480 Participants15 Participants4 Participants6 Participants9 Participants413 Participants1 Participants24 Participants1 Participants3 Participants4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
31 Participants2 Participants0 Participants0 Participants0 Participants28 Participants0 Participants1 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
2 Participants0 Participants0 Participants0 Participants0 Participants2 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
13 Participants0 Participants0 Participants0 Participants0 Participants13 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
20 Participants0 Participants0 Participants1 Participants1 Participants16 Participants0 Participants2 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
35 Participants2 Participants1 Participants0 Participants1 Participants31 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
486 Participants17 Participants5 Participants7 Participants8 Participants413 Participants3 Participants23 Participants3 Participants3 Participants4 Participants
Region of Enrollment
Belgium
29 participants0 participants0 participants0 participants0 participants29 participants0 participants0 participants0 participants0 participants0 participants
Region of Enrollment
Canada
27 participants0 participants0 participants0 participants0 participants27 participants0 participants0 participants0 participants0 participants0 participants
Region of Enrollment
France
14 participants0 participants0 participants0 participants0 participants14 participants0 participants0 participants0 participants0 participants0 participants
Region of Enrollment
Italy
35 participants0 participants0 participants0 participants0 participants35 participants0 participants0 participants0 participants0 participants0 participants
Region of Enrollment
Poland
23 participants0 participants0 participants0 participants0 participants23 participants0 participants0 participants0 participants0 participants0 participants
Region of Enrollment
Spain
47 participants0 participants0 participants0 participants0 participants47 participants0 participants0 participants0 participants0 participants0 participants
Region of Enrollment
United Kingdom
6 participants0 participants0 participants0 participants0 participants6 participants0 participants0 participants0 participants0 participants0 participants
Region of Enrollment
United States
376 participants19 participants6 participants8 participants10 participants295 participants3 participants25 participants3 participants3 participants4 participants
Sex: Female, Male
Female
221 Participants5 Participants0 Participants0 Participants1 Participants207 Participants1 Participants5 Participants0 Participants0 Participants2 Participants
Sex: Female, Male
Male
336 Participants14 Participants6 Participants8 Participants9 Participants269 Participants2 Participants20 Participants3 Participants3 Participants2 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
deaths
Total, all-cause mortality
2 / 41 / 32 / 310 / 251 / 3291 / 4762 / 103 / 81 / 65 / 19
other
Total, other adverse events
4 / 43 / 33 / 325 / 253 / 3468 / 47610 / 108 / 86 / 619 / 19
serious
Total, serious adverse events
2 / 40 / 31 / 39 / 252 / 3213 / 4766 / 105 / 82 / 68 / 19

Outcome results

Primary

Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window

Part 1of the study was a dose-escalation phase that evaluated the safety and tolerability and defined the maximum tolerated dose or recommended Phase 2 dose of the NKTR-214/nivolumab doublet across 5 dosage/schedule levels. The results presented are for the DLT Population.

Time frame: Includes DLTs that occurred within the DLT window of at least 21 days after the first dose of study treatment (28 days for every 2 weeks dosing; 21 days for every 3 weeks dosing). Patients were counted only once under each preferred term.

Population: The DLT population included all Part 1 patients who took study treatment and followed up at least through the DLT evaluation period (q2w dosing: received ≥ 2 cycles of study treatment and stayed in study for at least 28 days; q3w dosing: received at least 1 cycle of study treatment and stayed in study for at least 21 days) or discontinued from study treatment due to DLT.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowAt least 1 DLT0 Participants
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Acidosis0 Participants
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Hyperglycaemia0 Participants
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowVascular Disorders: Hypotension0 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowAt least 1 DLT0 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowVascular Disorders: Hypotension0 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Acidosis0 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Hyperglycaemia0 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowVascular Disorders: Hypotension0 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Acidosis0 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Hyperglycaemia0 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowAt least 1 DLT0 Participants
Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowAt least 1 DLT0 Participants
Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Acidosis0 Participants
Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowVascular Disorders: Hypotension0 Participants
Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Hyperglycaemia0 Participants
Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowVascular Disorders: Hypotension1 Participants
Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Hyperglycaemia1 Participants
Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and Nutrition Disorders: Acidosis1 Participants
Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3wPart 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowAt least 1 DLT2 Participants
Primary

Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)

Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) at Recommended Phase 2 Dose (RP2D). ORR is defined as the percentage of enrolled participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.

Time frame: Tumor assessment at Screening then every 8 weeks (± 7 days) from Cycle 1 Day 1 and end of treatment (unless scan done within 4 weeks) up to approximately 27 months.

Population: The response evaluable population included patients who had measurable disease (per RECIST 1.1) at baseline and also had at least 1 postbaseline assessment of tumor response prior to receiving new systemic anticancer therapy, surgical procedures or radiotherapy on target lesions.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)64 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)3 Participants
Primary

Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window

Part 3 of the study was a schedule finding phase to establish the recommended phase 2 dosing schedules for Part 4 and assess the safety and tolerability for the NKTR-214/nivolumab/ipilimumab triplet combination. The results presented are for the DLT Population.

Time frame: Dose-limiting toxicities (DLTs) were assessed during a 3-week (21-day) DLT evaluation period beginning with the first dose of ipilimumab.

Population: The DLT population included all Part 3 patients who received at least 1 cycle of study treatment and stayed in study for at least 21 days after first dose of ipilimumab or discontinued from study treatment due to DLT.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowPatients with at least one event1 Participants
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowEndocrine disorders: Adrenal insufficiency0 Participants
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowEndocrine disorders: Hyperthyroidism0 Participants
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and nutrition disorders: Hyponatraemia1 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and nutrition disorders: Hyponatraemia0 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowPatients with at least one event1 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowEndocrine disorders: Hyperthyroidism0 Participants
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowEndocrine disorders: Adrenal insufficiency1 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowMetabolism and nutrition disorders: Hyponatraemia0 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowEndocrine disorders: Adrenal insufficiency0 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowEndocrine disorders: Hyperthyroidism1 Participants
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2wPart 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation WindowPatients with at least one event1 Participants

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026