Pembrolizumab + CVA21 in Advanced NSCLC

NCT02824965 | Unknown Phase 1 DMC

• 1 other identifier: ONJ2015-001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a Phase Ib open-label trial of CAVATAK™ (CVA21) in combination with Pembrolizumab for the treatment of patients with advanced NSCLC. The dose of Pembrolizumab will be fixed at 200mg. Three cohorts (dose levels) of intravenously-delivered CVA21 will be explored, using a standard 3+3 patient dose escalation design. The starting dose of CVA21 will be one log below the 1 x 10\^9 TCID50 dose found to be safe when CVA21 was given alone in an ongoing Phase I study (NCT02043665).

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].

  To evaluate the safety of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC. All adverse events will be collected and assessed with regards to CTCAE V4.0 grading, seriousness, duration and relationship to the study drugs.

  0-24 months

Secondary Outcomes (6)

• ORR from the date of first study treatment as assessed by RECIST

  0-24 months

• ORR from the date of first study treatment as assessed by immune related response criteria (irRC)

  0-24 Months

• PFS

  0-36 Months

• Incidence of detectable CVA21 virus and neutralizing antibodies

  0-24 Months

• OS

  0-36 Months

Study Arms (1)

Pembrolizumab+1x10^9 TCID50 CVA21

EXPERIMENTAL

CVA21 will be administered IV on days: 1, 3, 5, 8 29, 50, 71, 92, 113 134, and 155. 200mg Pembrolizumab will be administered as per normal dosing frequency at Q3W IV, and will continue for up to 24 months. Should dose limiting toxicities be observed participants may be transferred a lower dosage of CVA21.

Drug: Pembrolizumab; Biological: CVA21

Interventions

Pembrolizumab DRUG

Pembrolizumab is a selective monoclonal antibody that blocks the interaction between PD1 and its ligands PDL1 and PDL2, resulting in infiltration of tumour specific CD8+ T-cells and ultimately leads to tumour rejection.

Also known as: KEYTRUDA

Pembrolizumab+1x10^9 TCID50 CVA21

CVA21 BIOLOGICAL

CAVATAK is an oncolytic Coxsackie virus that specifically infects and kills ICAM overexpressing tumour cells

Also known as: CAVATAK, Coxsackie virus 21

Pembrolizumab+1x10^9 TCID50 CVA21

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
• Have a performance status of 0 - 1 on the ECOG Performance Scale.
• Histologically confirmed NSCLC.
• No CVA21 neutralising antibody (≤ 1:16).
• Life expectancy \> 3 months.
• Acceptable haematological, renal and hepatic function.
• Protocol approved by local Research Ethics Committees.
• No chemotherapy, radiation therapy, hormonal treatment of immunotherapy within 28 days of dosing, except small doses of RT (\<20 Gy) given for symptomatic bone metastases.
• Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If subject received major surgery or radiation therapy of \> 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in section 6.13.2, starting with the first dose of study drug therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has active cardiac disease.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has a history of interstitial lung disease.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Olivia Newton-John Cancer Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator
• Viralytics: collaborator

Study Sites (1)

Austin Health

Heidelberg, Victoria, 3078, Australia

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Thomas John

  Austin Health

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 13, 2016
• First Posted: July 7, 2016
• Study Start: August 9, 2017
• Primary Completion: July 1, 2021
• Study Completion: October 1, 2021
• Last Updated: July 7, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)