Study of VB10.NEO in Combination With Atezolizumab in Solid Tumors

• ClinicalTrials.gov Identifier: NCT05018273
• Recruitment Status: Recruiting
• First Posted: August 24, 2021
• Last Update Posted: February 10, 2022
• Sponsor: Nykode Therapeutics AS
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Nykode Therapeutics AS

Study Description

Brief Summary:

A phase 1b, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, antigen-specific immune response and preliminary antitumor activity associated with VB10.NEO administered in combination with atezolizumab, and to identify a RP2D for VB10.NEO in combination with atezolizumab, in patients with locally advanced and metastatic tumors that have progressed after at least 1 available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized standard of care (SOC).

Condition or disease	Intervention/treatment	Phase
Solid Tumors, Adult	Biological: VB10.NEO	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1B, Open-Label, Dose-Escalation Study of the Safety of and Antigen-specific Immune Responses Elicited by VB10.NEO in Combination With Atezolizumab in Patients With Locally Advanced and Metastatic Tumors
• Actual Study Start Date: December 21, 2021
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: VB10.NEO 3 mg in combination with Atezolizumab 1200 mg; VB10.NEO 3 mg will be administered by IM injection for an induction course Q3W (4 doses) followed by maintenance doses Q6W (6 doses) and Q12W (5 doses). Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of 21 day cycles.	Biological: VB10.NEO; The personalized vaccine VB10.NEO vaccine is given in combination with the PD-L1 inhibitor atezolizumab.; Other Names: Atezolizumab; Tecentriq
Experimental: VB10.NEO 6 mg in combination with Atezolizumab 1200 mg; VB10.NEO 6 mg will be administered by IM injection for an induction course Q3W (4 doses) followed by maintenance doses Q6W (6 doses) and Q12W (5 doses). Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of 21 day cycles.	Biological: VB10.NEO; The personalized vaccine VB10.NEO vaccine is given in combination with the PD-L1 inhibitor atezolizumab.; Other Names: Atezolizumab; Tecentriq

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of adverse events (AEs) [ Time Frame: From baseline and up to 27 months ]
   The number and percentage of participants that experience an adverse event (AE)
2. Changes from baseline in vital signs [ Time Frame: From baseline and up to 27 months ]
   Changes for measurements done prior and after the first VB10.NEO injection of each cycle for the following vital signs: Systolic blood pressure (mmHg); diastolic blood pressure (mmHg); pulse rate (bpm); respiration rate (breaths/min); body temperature (°C)
3. Changes from baseline in clinical laboratory parameters [ Time Frame: From baseline and up to 27 months ]
   Changes for clinical laboratory parameters analysed locally prior and after the first VB10.NEO injection of each cycle, including hematology, chemistry panel, coagulation, thyroid function testing, C-reactive protein, urinalysis and serology

Secondary Outcome Measures :

1. Assessment of the antigen-specific immune response elicited by VB10.NEO administered in combination with atezolizumab [ Time Frame: From baseline and up to 25 months ]
   Number and magnitude of antigen-specific T-cell responses before and after initiation of trial treatment
2. Objective response rate (ORR) [ Time Frame: From baseline and up to 27 months ]
   The proportion of subjects with a complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
3. Duration of response (DOR) [ Time Frame: From baseline and up to 27 months ]
   The time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
4. Progression free survival (PFS) [ Time Frame: From baseline and up to 27 months ]
   The time from the first trial treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
5. Overall survival (OS) [ Time Frame: From baseline and up to 27 months ]
   The time from the first trial treatment to death from any cause
6. Characterize the pharmacokinetic of atezolizumab when administered in combination with VB10.NEO. [ Time Frame: From baseline and up to 25 months ]
   Serum concentration of atezolizumab at specified timepoints
7. Evaluate the immune response to atezolizumab when administered in combination with VB10.NEO [ Time Frame: From baseline and up to 25 months ]
   Prevalence of antidrug antibodies (ADAs) to atezolizumab at baseline and incidence of ADAs to atezolizumab

Other Outcome Measures:

1. Dose finding objective [ Time Frame: Through study completion, an average of 2 years. ]
   Identify a recommended phase 2 dose (RP2D) and regimen for VB10.NEO in combination with atezolizumab by evaluating the relationship between VB10.NEO dose and safety, biomarker, and antitumor activity endpoints

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Tumor types: melanoma, NSCLC, RCC, UC, HNSCC, TNBC, gastric/GEJ cancer, cervical, anal, or MSI-high tumors. Additionally up to 10 subjects with other locally advanced or metastatic solid tumor types not listed above.

Signed Informed Consent Form

Age ≥18 years at time of signing the Informed Consent Form

Life expectancy ≥ 6 months

Ability to comply with the trial protocol

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of trial treatment:

ANC ≥1.5 × 109/L (1500/µL) without granulocyte colony-stimulating factor support

Lymphocyte count ≥0.5 × 109/L (500/µL)

Platelet count ≥100 × 109/L (100,000/µL) without transfusion

Hemoglobin ≥90 g/L (9 g/dL)

Subjects may be transfused to meet this criterion.

AST and ALT ≤3 × ULN

Alkaline phosphatase (ALP) ≤2.5 × ULN, with the following exceptions:

Subjects with documented liver or bone metastases: ALP ≤5 × ULN

Total bilirubin ≤1.5 × ULN with the following exception:

Subjects with known Gilbert disease: total bilirubin ≤3 × ULN

Measured or calculated creatinine clearance ≥50 mL/min (according to the Cockcroft-Gault formula)

Albumin ≥25 g/L (2.5 g/dL)

For subjects not receiving therapeutic anticoagulation: International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN

For subjects receiving therapeutic anticoagulation: stable anticoagulant regimen

Female subjects of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of trial treatment.

Female subjects of childbearing potential must agree to use a highly effective form of contraception during treatment and for at least 90 days after the final dose of VB10.NEO, and for 5 months after the final dose of atezolizumab, whichever occurs later. Highly effective forms of contraception include:

combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal

progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable

intrauterine device

intrauterine hormone-releasing system

bilateral tubal occlusion

vasectomized partner

sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence [calendar, symptothermal, post-ovulation methods], withdrawal [coitus interruptus], spermicides only, and the lactational amenorrhea method are not acceptable methods of contraception).

For men with a female partner of childbearing potential or pregnant female partner: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom during the treatment period and for at least 28 days after the final dose of trial treatment to avoid exposing the embryo, and agreement to refrain from donating sperm. Histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least 1 available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized SOC.

Exclusion Criteria:

Pregnant or breastfeeding, or intending to become pregnant during the trial or within 90 days after the last dose of VB10.NEO or 5 months after the last dose of atezolizumab, whichever occurs later

Significant cardiovascular disease such as, but not limited to, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina

QT interval corrected through use of Fridericia's formula (QTcF) >470ms demonstrated by at least 2 electrocardiograms (ECGs) >30 minutes apart

Clinically significant liver disease including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse

Positive hepatitis B surface antigen (HBsAg) test at screening

Subjects with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive IgG antibody to hepatitis B core antigen) are eligible.

Positive hepatitis C virus (HCV) antibody test at screening

Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)

Positive human immunodeficiency virus (HIV)-1 test at screening

Active tuberculosis

Any other diseases, metabolic dysfunction, physical examination finding, and/or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or may render the subject at high risk from treatment complications

Known primary immunodeficiencies

Active, or history of, autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

Subjects with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the trial.

Subjects with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the trial.

Subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) are eligible for the trial provided all of the following conditions are met:

Rash must cover <10% of body surface area

Disease is well controlled at baseline and requires only lowpotency topical corticosteroids

No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months

History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.

Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.

Known allergy or hypersensitivity to any component of the VB10.NEO formulation.

History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on imaging conducted for tumor assessment at screening

History of radiation pneumonitis in the radiation field (fibrosis) is permitted

History of drug-induced pneumonitis that was asymptomatic (defined by radiographic findings only) and reversible (without any anti-inflammatory therapies) is permitted.

Severe infection within 28 days prior to Cycle 1, Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia

Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease [COPD] exacerbation) are eligible for the trial.

Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

Subjects with indwelling catheters (e.g., PleurX) are allowed.

Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected calcium >ULN)

Major surgical procedure within 28 days prior to Cycle 1, Day 1, or anticipation of need for a major surgical procedure during the course of the trial

Prior allogeneic stem cell or solid organ transplantation

Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 28 days or 5 drug-elimination half-lives (whichever is longer) prior to Cycle 1, Day 1

Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone >7.5 mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, and tumor necrosis factor-alpha [TNF-α] antagonists) within 2 weeks prior to Cycle 1, Day 1 with the following exceptions:

Subjects who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the trial after medical monitor confirmation has been obtained

Subjects who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the trial.

Treatment with investigational therapy within 28 days prior to Cycle 1, Day 1

Live, attenuated vaccines are prohibited within 28 days prior to Cycle 1, Day 1, during atezolizumab treatment, and for 5 months after the final dose of atezolizumab

Vaccination with an approved COVID-19 vaccine that does not contain live, attenuated virus is permitted

Contacts and Locations

Contacts

Contact: Siri Torhaug, MD; +4795113393; storhaug@nykode.com

Contact: Ane Stenstroem, MSc; astenstroem@nykode.com

Locations

United States, Kentucky

Norton Cancer Institute; Recruiting

Louisville, Kentucky, United States, 40202-1840

Contact: Jaspreet Grewal, MD

United States, Missouri

Washington University; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Nikolaos Trikalinos, MD

Germany

Charité-Universitätsmedizin Berlin; Recruiting

Berlin, Germany, 10117

Contact: Sebastian Ochsenreither, MD

Nationales Centrum für Tumorerkrankungen (NCT); Recruiting

Heidelberg, Germany

Contact: Juergen Krauss, MD, PhD

Spain

Hospital Universitario La Paz; Recruiting

Madrid, Spain

Contact: Beatriz Castelo, MD

Sponsors and Collaborators

Nykode Therapeutics AS

Genentech, Inc.

More Information

• Responsible Party: Nykode Therapeutics AS
• ClinicalTrials.gov Identifier: NCT05018273
• Other Study ID Numbers: VB N-02
• First Posted: August 24, 2021
• Last Update Posted: February 10, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nykode Therapeutics AS:

Locally advanced and metastatic tumors

Additional relevant MeSH terms:

Neoplasms; Atezolizumab; Antineoplastic Agents