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NKTR 214



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CAS  946414-94-4

  • BMS 936558
  • MDX 1106
  • NKTR 214
  • ONO 4538
  • Opdivio

Pegylated engineered interleukin-2 (IL-2) with altered receptor binding

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 (programmed cell death protein 1) on immune cells and promotes anti-tumor effects.

Protein Sequence

Sequence Length: 1308, 440, 440, 214, 214multichain; modified (modifications unspecified)

NKTR-214 is a CD122-biased cytokine in phase II clinical trials at the M.D. Anderson Cancer Center for the treatment of advanced sarcoma in combination with nivolumab.


M.D. Anderson Cancer Center, PHASE 2, SARCOMA

NKTR-214 in combination with OPDIVO® (nivolumab)

RESEARCH FOCUS: Immuno-oncology


In clinical collaboration withCollaborator

About NKTR-214, Nektar’s Lead Immuno-oncology Candidate

NKTR-214 is a CD122-biased agonist designed to stimulate the patient’s own immune system to fight cancer. NKTR-214 is designed to grow specific cancer-killing T cells and natural killer (NK) cell populations in the body which fight cancer, which are known as endogenous tumor-infiltrating lymphocytes (TILs). NKTR-214 stimulates these cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In preclinical studies, treatment with NKTR-214 results in a rapid expansion of these cells and mobilization into the tumor micro-environment. NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

In preclinical studies, NKTR-214 demonstrated a mean ratio of 450:1 within the tumor micro-environment of CD8-positive effector T cells, which promote tumor destruction, compared with CD4-positive regulatory T cells, which are a type of cell that can suppress tumor-killing T cells.2Furthermore, a single dose of NKTR-214 resulted in a 500-fold AUC exposure within the tumor compared with an equivalent dose of the existing IL-2 therapy, enabling, for the first time, an antibody-like dosing regimen for a cytokine.2 In dosing studies in non-human primates, there was no evidence of severe side effects such as low blood pressure or vascular leak syndrome with NKTR-214 at predicted clinical therapeutic doses.2 NKTR-214 has a range of potential uses against multiple tumor types, including melanoma (the most serious type of skin cancer), kidney cancer and non-small cell lung cancer (the most common form of lung cancer).

A Phase 1 study evaluating NKTR-214 as a single agent in patients with locally recurrent or metastatic solid tumors including melanoma, renal cell carcinoma (RCC), bladder, colorectal and other solid tumors is ongoing with patient enrollment complete. Results from this Phase 1 trial were presented at the Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting and showed encouraging evidence of anti-tumor activity, and a favorable safety and tolerability profile. (Poster #387)

In September 2016, Nektar entered into a clinical collaboration with Bristol-Myers Squibb to evaluate NKTR-214 as a potential combination treatment regimen with Opdivo (nivolumab) in five tumor types and eight potential indications. The Phase 1/2 PIVOT clinical trials, known as PIVOT-02 and PIVOT-04 will enroll up to 260 patients and will evaluate the potential for the combination of Opdivo (nivolumab) and NKTR-214 to show improved and sustained efficacy and tolerability above the current standard of care in melanoma, kidney, triple-negative breast cancer, bladder and non-small cell lung cancer patients.

In May 2017, Nektar entered into a research collaboration with Takeda to explore the combination of NKTR-214 with five oncology compounds from Takeda’s cancer portfolio including a SYK-inhibitor and a proteasome inhibitor. The collaboration will explore the anti-cancer activity of NKTR-214 combined with five different targeted mechanisms in preclinical tumor models of lymphoma, melanoma and colorectal cancer to identify which combination treatment regimens show the most promise for possible advancement into the clinic.

Under the terms of the collaboration, the companies will share costs related to the preclinical studies and each will contribute their respective compounds to the research collaboration. Nektar and Takeda will each maintain global commercial rights to their respective drugs and/or drug candidates.

Additional development plans for NKTR-214 include combination studies with additional checkpoint inhibitors, cell therapies and vaccines.

About the Excel NKTR-214 Phase 1/2 Study

The dose-escalation stage of the Excel Phase 1/2 study is designed to evaluate safety, efficacy, and define the recommended Phase 2 dose of NKTR-214 in approximately 20 patients with solid tumors. In addition to a determination of the recommended Phase 2 dose, the study will assess preliminary anti-tumor activity, including objective response rate (ORR). The immunologic effect of NKTR-214 on tumor-infiltrating lymphocytes (TILs) and other immune infiltrating cells in both blood and tumor tissue will also be assessed. Enrollment in the dose escalation study is completed. More information on the Excel Phase 1/2 study can be found on

About the PIVOT Phase 1/2 Program: NKTR-214 in combination with OPDIVO® (nivolumab)

The dose escalation stage of the PIVOT program (PIVOT-02 Phase 1/2 study) is underway and will determine the recommended Phase 2 dose of NKTR-214 administered in combination with nivolumab. The study is first evaluating the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab in approximately 30 patients with melanoma, renal cell carcinoma or non-small cell lung cancer. Once the recommended Phase 2 dose is achieved, the study will expand into additional patients for each tumor type. The second phase of the expansion cohorts in the PIVOT program (PIVOT-04 Phase 2 study) will evaluate safety and efficacy of the combination in up to 260 patients, in five tumor types and eight indications, including first and second-line melanoma, second-line renal cell carcinoma in immune-oncology therapy (IO) naïve and IO-relapsed patients, second-line non-small cell lung cancer in IO-naïve and IO-relapsed patients, first-line urothelial carcinoma, and second-line triple negative breast cancer. This study is expected to initiate in the second quarter of 2017.

Information on the PIVOT-02 study can be found on


About the PROPEL Phase 1/2 Program: NKTR-214 in combination with TECENTRIQ® (atezolizumab) or KEYTRUDA®(pembrolizumab)

The dose escalation stage of the PROPEL program will determine the recommended Phase 2 dose of NKTR-214 administered in combination with anti-PD-L1 agent, atezolizumab or anti-PD-1 agent, pembrolizumab. The study will evaluate the clinical benefit, safety and tolerability of combining NKTR-214 with atezolizumab or pembrolizumab and will enroll patients into two separate arms concurrently. The first arm will evaluate an every three-week 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 second arm will evaluate an every three-week dose regimen 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.

Information on the PROPEL study can be found on


1Boyman, J., et al., Nature Reviews Immunology, 2012, 12, 180-190.

2Charych, D., et al., Clin Can Res; 22(3) February 1, 2016

Inventors Murali Krishna AddepalliDeborah H. CharychSeema KantakSteven Robert Lee
Applicant Nektar Therapeutics (India) Pvt. Ltd.Nektar Therapeutics

////////////946414-94-4, BMS 936558, MDX 1106, NKTR 214, ONO 4538, Opdivio, NIVOLUMAB, PHASE 2

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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

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