This open labelled first in human dose phase 1/2a study is designed to evaluate safety, feasibility and efficacy of multiple dosing with individualised VB10.NEO and bempegaldesleukin (NKTR-214) immunotherapy in patients with locally advanced or metastatic solid tumours.
This open labelled first in human dose phase 1/2a study is designed to evaluate safety, feasibility and efficacy of multiple dosing with individualised VB10.NEO immunotherapy in patients with locally advanced or metastatic solid tumours including melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of the head and neck (SCCHN), who did not reach complete responses with immune checkpoint inhibitor (CPI) therapy as their standard of care (SOC) treatment. Patients with melanoma, NSCLC, RCC and urothelial carcinoma must upon screening, have been receiving a CPI (anti-PD-1 or anti-PD-L1) for at least 12 weeks as the patient's standard of care. Patients with SCCHN can be screened as long as they have initiated treatment with CPI as SOC. The VB10.NEO vaccine will be added to continuing CPI treatment and shall not replace, omit, postpone or terminate the standard therapy. Patients who have been treated with CPI for at least 12 weeks, will be enrolled in case of some benefit to CPI treatment is expected, as defined by partial response, stable disease or disease progression (in case of a mixed response to CPI, provided at least one lesion shows measurable regression and patient, according to the investigator, would have a clinical benefit of continued immunotherapy). The assumption is to combine the immuno-stimulating effect of CPIs with immune responses towards specific neo-antigens in the vaccine, which may possibly increase the anti-tumour effect to reach durable efficacy. One arm of the study patients with SCCHN will have the option to be treated with bempegaldesleukin (NKTR-214) in combination with personalised VB10.NEO. This arm is open for enrollment from November 2019. The study will be conducted in two parts. Part A will evaluate safety, feasibility and efficacy of individualised VB10.NEO and bempegaldesleukin (NKTR-214) immunotherapy in SCCHN patients. The expansion part B will explore efficacy and safety in further patients with selected types of cancer showing signs of efficacy during part A.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
VB10.NEO is a vaccine and is supplied as a sterile, ready to use solution (14 vaccinations will be given).
0.006 mg/kg bempegaldesleukin (NKTR-214) will be administered intravenously q4w for up to 11 doses starting from week 11 or at any dosing visit up to week 34 and for up to week 50 (up to 11 doses). The first 2 doses will be in a Q3W interval and following doses in Q4W intervals.
Charité Research Organisation, Campus Benjamin Franklin
Berlin, Germany
Krankenhaus Nordwest gGmbH
Frankfurt, Germany
Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle (Saale)
Halle, Germany
University Hospital Heidelberg, NCT, Im Neuenheimer Feld 460
Heidelberg, Germany
Rate of Adverse Events including SAEs (Safety/tolerability) of VB10.NEO and the combination of VB10.NEO and bempegaldesleukin (NKTR-214)
Total number, severity (CTCAE grade) of adverse events (AEs), and if AE is leading to treatment discontinuation.
Time frame: Up to 24 months
Immunogenicity by T-cell activity to each neoepitope of VB10.NEO and the combination of VB10.NEO and bempegaldesleukin (NKTR-214)
Descriptive analyses for each patient of the immune-response to each neoepiotope
Time frame: Up to 24 months
Objective Response Rate (ORR)
Description of tumor response by iRECIST at regular intervals
Time frame: Up to 24 months
Duration of Response (DOR)
Descriptive analysis of DOR by iRECIST at regular intervals
Time frame: Up to 24 months
Progression-free survival (PFS)
Descriptive analysis of PFS by iRECIST at regular intervals
Time frame: Up to 24 months
Survival at end of treatment (EoT) and end of study (EoS)
Proportion of patients who are alive at EoT and EoS
Time frame: At 14 months and 24 months
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Universitätsmedizin Mannheim
Mannheim, Germany
Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie
Munich, Germany