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BRIEF TITLE: Safety and Preliminary Efficacy of NKTR 214 and Anti-PD-L1 (Atezolizumab) in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer or Metastatic Non-Small Cell Lung Cancer

A Phase 1b, Open-label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combination With Anti-PD-1 (Pembrolizumab) or Anti-PD-L1 (Atezolizumab) in Patients With Locally Advanced or Metastatic Solid Tumors


  • Org Study ID: 16-214-05
  • Secondary ID:
  • NCT ID: NCT03138889
  • NCT Alias:
  • Sponsor: Nektar Therapeutics - Industry
  • Source: Nektar Therapeutics

Brief Summary

This study is to assess the safety and tolerability, define the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to assess the preliminary clinical benefit of NKTR-214 when combined with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®). Up to 30 patients will be enrolled concurrently in each combination arm. NKTR-214 in combination with pembrolizumab will be evaluated in select patients with metastatic melanoma, urothelial bladder cancer or non-small cell Lung cancer (NSCLC). NKTR-214 in combination with atezolizumab will be evaluated in select patients with urothelial bladder cancer or NSCLC. Both drugs target the immune system and may act synergistically to promote anticancer 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. Pembrolizumab is a programmed death
receptor -1 (PD-1) blocking antibody and atezolizumab is a fully humanized, engineered
monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1
(PD-L1) that promotes anti-tumor effects.

The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214
with pembrolizumab or atezolizumab and will enroll approximately 60 patients into two
separate arms concurrently. The first arm will evaluate an every three-week dose regimen
(q3w) of NKTR-214 in combination with pembrolizumab in up to 30 patients in approved
treatment settings of pembrolizumab, including patients with melanoma, non-small cell lung
cancer or bladder cancer. The second arm will evaluate a q3w dose regimen of NKTR-214 in
combination with atezolizumab in up to 30 patients in approved treatment settings of
atezolizumab, including patients with non-small cell lung cancer or bladder cancer. The first
NKTR-214 dose to be studied will be 0.006 mg/kg q3w based on the safety observed in the
monotherapy trial with NKTR-214 (Study 15-214-01, NCT02869295).

For NKTR-214 + Pembrolizumab, eligible patients include:

- Melanoma: 1st line; PD-L1 Status- all

- NSCLC: 1st line; PD-L1 Status ≥ 50%

- NSCLC: 2nd line; PD-L1 Status ≥ 1%

- Urothelial carcinoma (cisplatin ineligible): 1st line; PD-L1 Status - all

- Urothelial carcinoma: 2nd line; PD-L1 Status - all

For NKTR-214 + Atezolizumab, eligible patients include:

- NSCLC: 2nd line; PD-L1 Status - all

- Urothelial carcinoma: 1st line; PD-L1 Status - all

- Disease progression within 12 months of neoadjuvant or adjuvant treatment with
chemotherapy

- Urothelial carcinoma: 2nd line; PD-L1 Status - all

Overal Status Start Date Phase Study Type
Recruiting June 9, 2017 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)

Primary Outcome 1 - Time Frame: 100 days after last dose

Primary Outcome 2 - Measure: Recommended Phase 2 Dose (RP2D) of NKTR-214 in combination with pembrolizumab (Keytruda®) or atezolizumab (Tecentriq®)

Primary Outcome 2 - Time Frame: 100 days after last dose

Condition:

  • Non-Small Cell Lung Cancer
  • Urinary Bladder Neoplasms
  • Neoplasm Metastasis
  • Melanoma

Eligibility

Criteria:
Inclusion Criteria:

- Willing and able to provide written informed consent.

- Histologically confirmed locally advanced melanoma (pembrolizumab only), locally
advanced or metastatic urothelial carcinoma, or metastatic NSCLC.
<br/> - Male or female patients, age 18 years or older at the time of signing the informed
consent form (ICF).

- 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 must not have received prior oncology regimens, including but not limited to
inhibitors such as anti PD-1, anti-PD-L1, anti-PD-L2, anti CD137, or anti CTLA-4
(cytotoxic T lymphocyte-associated protein 4) antibody, or any other antibody or drug
specifically targeting T cell co stimulation or checkpoint pathways, indoleamine
2,3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or other
cytokine therapies.

- MELANOMA (pembrolizumab only)

- Histologically confirmed stage III (unresectable) or stage IV melanoma, as per
American Joint Committee on Cancer (AJCC) staging system

- Ocular melanoma is excluded

- Have not received prior anti-cancer therapy for advanced or metastatic melanoma

- Patients with unknown BRAF mutation status may enroll so long as mutation testing
is planned to be performed within 30 days of Cycle 1 Day 1

- NSCLC

- Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC

- First-line (pembrolizumab only), patients must have high PD-L1 expression (Tumor
Proportion Score [TPS] ≥ 50%) as determined by FDA-approved test, with no
epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)
genomic tumor aberrations.

- Second-line (pembrolizumab or atezolizumab), patients must have experienced
disease recurrence or progression during or after a prior platinum-based
chemotherapy given for advanced or metastatic disease. Patients with EGFR or ALK
genomic tumor aberrations should have disease progression on FDA-approved therapy
for these aberrations and must not have received chemotherapy.

- If patient is to receive pembrolizumab in combination with NKTR 214, PD L1 expression
by TPS should be ≥ 1% as determined by an FDA-approved test.

- UROTHELIAL CARCINOMA

- Histologically or cytologically documented locally advanced or metastatic
urothelial carcinoma

- First-line (pembrolizumab only), patients who are not eligible for
cisplatin-containing chemotherapy.

- First-line (atezolizumab only), patients who have disease progression within 12
months of neoadjuvant or adjuvant treatment with chemotherapy.

- Second-line (pembrolizumab or atezolizumab), patients who have disease
progression during or following platinum-containing chemotherapy.

- Additional criteria may apply.

Exclusion Criteria:

- Use of an investigational agent or an investigational device within 28 days before
administration of first dose of study drug(s).

- Females who are pregnant or breastfeeding.

- Patients who have an active, known or suspected autoimmune disease. Patients requiring
systemic treatment within the past 3 months or a documented history of clinically
severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
(Exceptions include any patient on 10 mg or less of prednisone or equivalent, patients
with vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves'
disease, Hashimoto's disease, alopecia areata, eczema, or with Medical Monitor
approval).

- History of allergy or hypersensitivity to study drug components.

- Active malignancy not related to the current diagnosed malignancy.

- History of organ transplant that requires use of immune suppressive agents.

- Use of warfarin within 14 days of initiating study drug(s). (Note: Low molecular
weight heparin is allowed on the study.)

- 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.

- Additional criteria may apply
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Michael Imperial, MD

Role: Study Director

Affiliation: Nektar Therapeutics

Overall Contact

Name: Nektar Recruitment

Phone: 855-482-8676

Email: StudyInquiry@nektar.com

Locations

Facility Status Contact
Investigator Site - New Orleans
New Orleans, Louisiana 70816
United States
Recruiting
Investigator Site - Omaha
Omaha, Nebraska 68198
United States
Recruiting
Investigator Site - Las Vegas
Las Vegas, Nevada 89169
United States
Recruiting
Investigator Site - Germantown
Memphis, Tennessee 38138
United States
Recruiting
Investigator Site - Tacoma
Tacoma, Washington 98405
United States
Recruiting