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.

Brief Title

A Study to Evaluate Safety and Efficacy of Multiple Dosing With VB10.NEO and Bempegaldesleukin (NKTR-214) Immunotherapy in Patients With Locally Advanced or Metastatic Cancer

Official Title

An Open Labelled First Human Dose Phase 1/2a Study to Evaluate Safety, Feasibility, Efficacy of Multiple Dosing With Individualised VB10.NEO and Bempegaldesleukin (NKTR-214) Immunotherapy in Patients With Locally Advanced or Metastatic Melanoma, Non-small Cell Lung Cancer (NSCLC), Clear Renal Cell Carcinoma, Urothelial Cancer or Squamous Cell Carcinoma of Head and Neck, Who Did Not Reach Complete Responses With Current Standard of Care Immune Checkpoint Blockade

Brief Summary

This open labelled first in human dose phase 1/2a study is designed to evaluate safety, <br /> feasibility and efficacy of multiple dosing with individualised VB10.NEO and <br /> bempegaldesleukin (NKTR-214) immunotherapy in patients with locally advanced or metastatic <br /> solid tumours.

Detailed Description

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.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Inclusion criteria for all arms

  -  Have histologically confirmed locally advanced or metastatic melanoma, NSCLC, RCC,
     urothelial carcinoma or SCCHN.

  -  Patients must have been on CPI (i.e., anti-PD-1 or anti PD-L1) for at least 12 weeks
     before screening and must be on CPI treatment as part of their cancer treatment as
     prescribed by the treating physician.

Inclusion criteria for SCCHN only

• Patients must be on CPI or must initiate treatment with CPI at screening as part of their
cancer treatment.

All arms

  -  Patients who have been on CPI for longer than 12 weeks at screening need to be per
     RECIST:

       -  in partial response or;

       -  stable disease or,

       -  in progression, i.e., in case of a mixed response to CPI, provided at least one
          lesion shows measurable regression and who, according to the investigator, have a
          clinical benefit of continued immunotherapy.

  -  Adequate tumour specimen must be available for exome sequencing.

  -  Measurable disease per RECIST 1.1 criteria.

  -  ECOG performance status ≤ 1.

  -  Life expectancy at least 6 months in the best judgement of the investigator.

  -  Willing and able to sign a written informed consent form.

Exclusion criteria

  -  Ocular melanoma.

  -  Brain metastases (unless controlled and stable for at least 6 weeks) or leptomeningeal
     spread of disease.

  -  Positive serological test for hepatitis C virus or hepatitis B virus surface antigen
     (HBsAg) or human immunodeficiency virus (HIV).

  -  Other concomitant or prior malignant disease, except for adequately treated basal cell
     carcinoma or other non-melanomatous skin cancer, low-grade urothelial cancer or other
     malignancies treated with curative intent within 2 or more years pre-study entry and
     in complete remission at study entry

  -  Patients who have an active, known or suspected autoimmune disease. Patients having
     required systemic treatment within the past 3 months or have a documented history of
     clinically severe autoimmune disease that require systemic steroids or
     immunosuppressive agents (Exceptions include any patient on 10 mg or less of
     prednisolone or equivalent, patients with vitiligo, hypothyroidism stable on hormone
     replacement; type 1 diabetes, Grave's disease, Hashimoto's disease, alopecia areata,
     eczema).

  -  Immunosuppression including the continued use (> 7 days) of high-dose (>10 mg of
     prednisolone or equivalents) systemic steroids or the use of immunosuppressive agents
     for any concurrent condition.

Other protocol defined inclusion exclusion criteria may apply