Abstract 1026TiP
Background
NKTR-255 is a polymer-conjugated rhIL-15 agonist, which provides sustained pharmacodynamic responses without the need for daily dosing. Preclinical studies have shown that NKTR-255 induces the proliferation and activation of CD8+ T-cells and natural killer cells, increases the CD8+ to regulatory T-cell ratio, and enhances antitumor activity and survival both as monotherapy and when combined with monoclonal antibodies. This phase Ib/II dose-escalation and dose-expansion study (NCT04616196) evaluates the safety and antitumor activity of NKTR-255 plus cetuximab in patients with relapsed/refractory (R/R) head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).
Trial design
During the 7-day run-in period, patients receive a loading dose of IV cetuximab followed by IV NKTR-255 every 21 days plus cetuximab weekly. During dose-escalation, successive cohorts each receive ascending doses of NKTR-255 until the MTD and/or RP2D is determined. Patients with a partial or complete response (per RECIST v1.1) may continue with NKTR-255 maintenance therapy. During dose-expansion, NKTR-255 plus cetuximab will be evaluated in either Cohort A (R/R HNSCC) or Cohort B (R/R CRC). Patients ≥18 years are required to have histologically or cytologically confirmed disease, a life expectancy of >12 weeks, and an ECOG PS of 0 or 1. Patients with HNSCC must have progressed on any first-line or second-line platinum-based chemotherapy and/or anti-PD-(L)1 antibody treatment. Patients with CRC must have received or be intolerant to ≥2 prior regimens for metastatic disease; and those with a microsatellite instability-high or mismatched repair disease tumor must have received prior checkpoint inhibitor therapy. The primary endpoints are safety, tolerability, MTD, RP2D, and objective response rate (RECIST v1.1). Secondary endpoints include progression-free survival and overall survival. This trial is currently enrolling in the United States and plans to open in Europe for phase II. The planned enrollment is 78 patients.
Clinical trial identification
NCT04616196.
Editorial acknowledgement
Editorial assistance was provided by Sara Shaw PhD of BOLDSCIENCE Inc. Ltd., funded by Nektar Therapeutics, San Francisco, CA.
Legal entity responsible for the study
Nektar Therapeutics, San Francisco, CA.
Funding
Nektar Therapeutics, San Francisco, CA.
Disclosure
M. Altan: Other, Personal, Advisory Role: GlaxoSmithKline; Other, Personal, Advisory Role: Shattuck Labs; Financial Interests, Institutional, Funding, Research Funding: Lilly; Financial Interests, Institutional, Funding, Research Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding, Research Funding: Novartis; Financial Interests, Institutional, Funding, Research Funding: Jounce Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Adaptimmune; Financial Interests, Institutional, Funding, Research Funding: Merck; Financial Interests, Institutional, Funding, Research Funding: Genentech; Financial Interests, Institutional, Funding, Research Funding: Nektar Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Shattuck Labs; Financial Interests, Institutional, Funding, Research Funding: GlaxoSmithKline. A. Patnaik: Other, Personal, Advisory Role: Bayer; Other, Personal, Advisory Role: Novartis; Other, Personal, Advisory Role: Merck; Other, Personal, Advisory Role: Seattle Genetics; Other, Personal, Advisory Role: Silverback Therapeutics; Financial Interests, Personal, Advisory Role, Honoraria: Texas Society of Clinical Oncology; Financial Interests, Institutional, Funding, Research funding: Merck; Financial Interests, Institutional, Funding, Research funding: Pfizer; Financial Interests, Institutional, Funding, Research funding: Lilly; Financial Interests, Institutional, Funding, Research funding: Plexxikon; Financial Interests, Institutional, Funding, Research funding: Corvus Pharmaceuticals; Financial Interests, Institutional, Funding, Research funding: Tesaro; Financial Interests, Institutional, Funding, Research funding: Abbvie; Financial Interests, Institutional, Funding, Research funding: Forty Seven; Financial Interests, Institutional, Funding, Research funding: Five Prime Therapeutics; Financial Interests, Institutional, Funding, Research funding: Infinity Pharmaceuticals; Financial Interests, Institutional, Funding, Research funding: Pieris Pharmaceuticals; Financial Interests, Institutional, Funding, Research funding: Surface Oncology; Financial Interests, Institutional, Funding, Research funding: Livzon; Financial Interests, Institutional, Funding, Research funding: Vigeo Therapeutics; Financial Interests, Institutional, Funding, Research funding: Astellas Pharma; Financial Interests, Institutional, Funding, Research funding: Klus Pharma; Financial Interests, Institutional, Funding, Research funding: Symphogen; Financial Interests, Institutional, Funding, Research funding: Syndax; Financial Interests, Institutional, Funding, Research funding: Arcus Ventures; Financial Interests, Institutional, Funding, Research funding: Fochon Pharmaceuticals; Financial Interests, Institutional, Funding, Research funding: Upsher-Smith; Financial Interests, Institutional, Funding, Research funding: Exelixis; Financial Interests, Institutional, Funding, Research funding: Seattle Genetics; Financial Interests, Institutional, Funding, Research funding: Bolt; Financial Interests, Institutional, Funding, Research funding: Ionova; Financial Interests, Institutional, Funding, Research funding: Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding: Sanofi; Other, Personal, Other, Immediate Family Member: Bristol-Myers Squibb; Other, Personal, Other, Immediate Family Member: Genentech/Roche; Other, Personal, Other, Immediate Family Member: Merck. L. Dunn: Other, Personal, Advisory Role: Regeneron; Other, Personal, Advisory Role: CUE Biopharma; Financial Interests, Personal, Funding, Research Funding: Pfizer; Financial Interests, Personal, Funding, Research Funding: Regeneron; Financial Interests, Personal, Funding, Research Funding: Eisai. P.W. Cobb: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Stocks/Shares: Boston Scientific; Financial Interests, Personal, Stocks/Shares: Johnson&Johnson; Financial Interests, Personal, Stocks/Shares: United Health Group; Financial Interests, Personal, Stocks/Shares: Abbott Laboratories; Financial Interests, Personal, Stocks/Shares: Medtronic; Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Stocks/Shares: Crispr Therapeutics; Financial Interests, Personal, Stocks/Shares: Intuitive Surgical; Financial Interests, Personal, Stocks/Shares: Siemens; Financial Interests, Personal, Stocks/Shares: Thermo Fischer Scientific; Financial Interests, Institutional, Funding, Research Funding: Spectrum Pharmaceuticals; Financial Interests, Institutional, Funding, Research Funding: Acerta Pharma; Financial Interests, Institutional, Funding, Research Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding, Research Funding: Pfizer; Financial Interests, Institutional, Funding, Research Funding: AstraZeneca; Financial Interests, Institutional, Funding, Research Funding: Merck; Financial Interests, Institutional, Funding, Research Funding: Celgene; Financial Interests, Institutional, Funding, Research Funding: Pharmacyclics; Financial Interests, Institutional, Funding, Research Funding: Novartis; Financial Interests, Institutional, Funding, Research Funding: Galera Therapeutics; Financial Interests, Institutional, Funding, Research Funding: TG Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Incyte; Financial Interests, Institutional, Funding, Research Funding: Bayer; Financial Interests, Institutional, Funding, Research Funding: Boston Biomedical; Financial Interests, Institutional, Funding, Research Funding: Genentech/Roche; Financial Interests, Institutional, Funding, Research Funding: United Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Sanofi; Financial Interests, Institutional, Funding, Research Funding: Takeda; Financial Interests, Institutional, Funding, Research Funding: Odonate Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Nektar; Financial Interests, Institutional, Funding, Research Funding: Seattle Genetics; Financial Interests, Institutional, Funding, Research Funding: Ayala Pharmaceuticals; Financial Interests, Institutional, Funding, Research Funding: Altor; Financial Interests, Institutional, Funding, Research Funding: Isofol Medical; Financial Interests, Institutional, Funding, Research Funding: Decibel Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Aptose Biosciences; Financial Interests, Institutional, Funding, Research Funding: Innocare; Financial Interests, Institutional, Funding, Research Funding: Abbvie; Financial Interests, Institutional, Funding, Research Funding: Fochon Pharma; Financial Interests, Institutional, Funding, Research Funding: MEI Pharma; Financial Interests, Institutional, Funding, Research Funding: Viracta Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Ipsen; Financial Interests, Institutional, Funding, Research Funding: Mirati Therapeutics. A. Rosenberg: Other, Personal, Advisory Role: Nanobiotix; Other, Personal, Advisory Role: EMD Serono. S. Sharma: Other, Personal, Advisory Role: Dracen; Other, Personal, Advisory Role: Bauerfiend; Other, Personal, Advisory Role: Elevar Therapeutics; Other, Personal, Advisory Role: Celularity; Other, Personal, Other, Travel, Accommodation, Expenses: Bauerfiend; Financial Interests, Personal, Stocks/Shares: Beta Cat Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Salarius Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: ConverGene; Financial Interests, Personal, Stocks/Shares: Stingray Therapeutics; Financial Interests, Personal, Stocks/Shares: Elevar Therapeutics; Financial Interests, Personal, Stocks/Shares: HLB; Financial Interests, Personal, Stocks/Shares: Bauerfield; Financial Interests, Personal, Other, Honoraria: Array BioPharm; Financial Interests, Personal, Funding, Research Funding: Plexxikon; Financial Interests, Personal, Funding, Research Funding: AADi; Financial Interests, Personal, Funding, Research Funding: Syndax; Financial Interests, Personal, Funding, Research Funding: Merck; Financial Interests, Personal, Funding, Research Funding: Honor Health; Financial Interests, Personal, Funding, Research Funding: Novartis; Financial Interests, Personal, Funding, Research Funding: Inhibrx; Financial Interests, Personal, Funding, Research Funding: City of Hope; Financial Interests, Personal, Funding, Research Funding: Takeda; Financial Interests, Personal, Funding, Research Funding: Dracen; Financial Interests, Personal, Funding, Research Funding: Amal Therapeutics; Financial Interests, Personal, Licensing Fees, Provisional Application No. 62/961,930: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Licensing Fees, International PCT Application No. PCT/US20/13618: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Licensing Fees, Provisional application number: 62/818,037: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Licensing Fees, Provisional Application Serial No.: 63/005,780: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Licensing Fees, Provisional Application Serial No.: 63/018,059: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Licensing Fees, Provisional Application No.: 63/079,951: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Licensing Fees, Provisional Application No.: 63/079,954: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Licensing Fees, Provisional Application No.: 63/079,955: Patents, Royalties, Other Intellectual Property. A. Sukari: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb Foundation. Z. Lee: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. M.Q. Marcondes: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. J. Zalevsky: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. M.A. Tagliaferri: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. B. Kotzin: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. A.G. Sacco: Financial Interests, Institutional, Funding, Research Funding: Pfizer, EMD Serono; Financial Interests, Institutional, Funding, Research Funding: Merck. All other authors have declared no conflicts of interest.