First in Human Study of NG-350A (an Oncolytic Adenoviral Vector Which Expresses an Anti-CD40 Antibody)

NCT03852511 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: NG-350A-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

This study will evaluate the safety, tolerability and preliminary efficacy and also pharmacokinetics, immunogenicity and other pharmacodynamic effects to elucidate the mechanism of action of NG-350A, either alone or in combination with a check point inhibitor, in patients with advanced or metastatic epithelial tumours.

Conditions

Metastatic Cancer; Epithelial Tumor

Keywords

metastatic; epithelial; virus; advanced

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events, serious adverse events, adverse events meeting protocol-defined DLT criteria, severe adverse events, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.

  Characterise the safety and tolerability of NG-350A, in combination with a check point inhibitor, by reviewing reported Adverse Events (AEs) and Serious Adverse Events (SAEs).

  Throughout study to end of study treatment visit (Week 24 or +30 days after last study drug dose)

Study Arms (1)

Intravenous

EXPERIMENTAL

Patients will receive three single doses of NG-350A by IV infusion, followed by multiple cycles of check point inhibitor treatment.

Biological: NG-350A

Interventions

NG-350A BIOLOGICAL

NG-350A is oncolytic adenoviral vector which expresses a full length agonist anti-CD40 antibody at the site of virus replication.

Intravenous

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent to participate
• Aged 18 years or over
• Have one of eleven histologically or cytologically confirmed metastatic or advanced carcinomas or adenocarcinomas that have progressed after at least one line of systemic therapy and are incurable by local therapy
• a. Tumour types eligible are: UC, SCCHN, MSI high/dMMR cancer, NSCLC, uterine/endometrial cancer, cervical cancer, oesophageal cancer, gastric cancer, cutaneous squamous cell carcinoma, HCC and TNBC
• Additional tumour type specific criteria:
• UC: carcinoma of the renal pelvis, ureter, bladder, or urethra that showed predominantly transitional-cell features on histologic testing
• SCCHN with oropharyngeal cancer: known HPV p16 status
• MSI-high/dMMR cancer: MSI-high/dMMR status must be confirmed by an approved test
• NSCLC: either squamous or non-squamous histology
• Gastric cancer: gastric or gastroesophageal junction adenocarcinoma
• All patients enrolled in combination therapy cohorts with check point inhibitor (dose escalation and efficacy expansion phases) must have received prior treatment with a PD 1/PD-L1 inhibitor therapy (prior PD-1/PD-L1 may have been given as monotherapy or combination therapy)
• In combination dose-escalation, patients may have received a PD 1/PD L1 inhibitor as part of any prior line of therapy (additional criteria apply when this is the most recent line of therapy - see below)
• In dose expansion cohorts, patients must have been treated with a PD 1/PD-L1 inhibitor as part of their most recent treatment
• For all patients who received PD-1/PD-L1 inhibitor therapy as part of their most recent line of treatment (includes dose-escalation and all patients in dose-expansion), this must have been for a minimum of 6 weeks and maximum of 6 months, with best response of SD or PD - Patients with PD following treatment with a PD-1/PD-L1 inhibitor as their most recent therapy must have a \<50% increase in disease burden
• At least one measurable site of disease according to RECIST Version 1.1 criteria; this lesion must be either (i) outside a previously irradiated area or (ii) progressive if it is in a previously irradiated area

You may not qualify if:

• Prior or planned allogeneic or autologous bone marrow or organ transplantation
• Splenectomy
• Active infections requiring antibiotics, physician monitoring or systemic therapy within 1 week of the anticipated first dose of study drug, or recurrent fevers (\>38.0˚C) associated with a clinical diagnosis of active infection
• Active viral disease or positive test for hepatitis B virus using hepatitis B surface antigen test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. Positive test for HIV or AIDS
• Patients who have active autoimmune disease that has required systemic therapy in the past 2 years, are immunocompromised in the opinion of the Investigator, or are receiving systemic immunosuppressive treatment
• a. Patients with vitiligo, type I diabetes mellitus, asthma/atopy, residual hypothyroidism due to autoimmune disease (which only requires hormone replacement therapy), or conditions not expected to recur in the absence of an external trigger are permitted to enrol providing they comply with the other eligibility criteria relating to renal function. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed
• Treatment with any live, live attenuated or COVID-19 vaccine in the 28 days before the first dose of NG 350A
• Treatment with any other vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before first dose of NG-350A
• History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment
• History of clinically significant interstitial lung disease or non-infectious pneumonitis
• Lymphangitic carcinomatosis (clinically suspected or radiographic evidence)
• Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
• Myocardial infarction, stroke or other significant cardiovascular or cerebrovascular event in the 12 months before the first dose of study treatment
• Pulmonary embolism, deep vein thrombosis, or other uncontrolled thromboembolic event in the 12 months before the first dose of study treatment, or current treatment with therapeutic or prophylactic anticoagulation therapy
• Grade 3 or 4 gastrointestinal bleeding (or risk factors for gastrointestinal bleeding) or haemoptysis in the 3 months before first dose of study treatment, or any history of bleeding requiring an investigative procedure (e.g. endoscopy), transfusion or hospitalisation in the 12 months before the first dose of study treatment

Sponsors & Collaborators

• Akamis Bio: lead

Study Sites (5)

University of California, Los Angeles (UCLA)

Santa Monica, California, 90404, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10038, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Khalil DN, Prieto Gonzalez-Albo I, Rosen L, Lillie T, Stacey A, Parfitt L, Soff GA. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023 Apr;41(2):317-323. doi: 10.1007/s10637-023-01345-8. Epub 2023 Mar 10.

  PMID: 36897458 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma; Virus Diseases

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Infections

Study Officials

• Aung Naing, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients in Part A will receive a single cycle of NG-350A study treatment, with three single doses on Days 1, 3 and 5 by IV infusion. Patients in Part B will receive a single cycle of NG-350A study treatment, with three single doses on Days 1, 3 and 5 by IV infusion, followed by up to 8 cycles of a check point inhibitor.

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 25, 2019
• Study Start: February 19, 2019
• Primary Completion: February 4, 2022
• Study Completion: February 4, 2022
• Last Updated: June 24, 2022

Record last verified: 2022-06

Locations

US (5)