Study in Patients With Tumours Requiring Arginine to Assess ADI-PEG 20 With Atezolizumab, Pemetrexed and Carboplatin

NCT03498222 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 012375QM
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

iTRAP is an open-label, multi-centre, dose escalation study of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung carcinoma (NSCLC) - stage IIIB/IV.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Occurrence of dose limiting toxicities

  Protocol defined haematological events attributed as possibly, probably or definitely related to the study treatment.

  First 21 days of treatment

Study Arms (3)

Dose Level -1

EXPERIMENTAL

Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 9mg/m2

Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: ADI PEG20

Dose Level 1

EXPERIMENTAL

Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 18mg/m2

Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: ADI PEG20

Dose Level 2

EXPERIMENTAL

Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 36mg/m2

Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: ADI PEG20

Interventions

Atezolizumab DRUG

Administered at a fixed dose of 1200 mg (equivalent to an average body weight-based dose of 15mg/kg) by intravenous (IV) infusion every 3 weeks (21 days).

Also known as: Tecentriq

Dose Level -1; Dose Level 1; Dose Level 2

Pemetrexed DRUG

Administered at a fixed dose of 500mg/m2 by IV infusion every 3 weeks.

Also known as: Alimta

Dose Level -1; Dose Level 1; Dose Level 2

Carboplatin DRUG

Administered at a fixed dose of AUC5 by IV infusion every 3 weeks.

Dose Level -1; Dose Level 1; Dose Level 2

ADI PEG20 DRUG

Administered by intramuscular (IM) injection to patients once weekly.

Dose Level -1; Dose Level 1; Dose Level 2

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent prior to study entry.
• Age ≥ 18 years.
• Histologically proven advanced non-squamous NSCLC (stage IIIB/IV) not treated with chemotherapy or immunotherapy - immunotherapy for uveal melanoma and prior (neo)adjuvant chemotherapy is permitted. Patients with EGFR mutant or ALK positive NSCLC must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial.
• ASS1 deficiency defined as ≤50% ASS expression on tissue specimen by immunohistochemistry (IHC) (cytospin samples are acceptable) - assessed centrally. For patients previously treated with (neo)adjuvant chemotherapy, this specimen may have been obtained before that chemotherapy.
• Measurable disease as assessed by RECIST 1.1 i.e. at least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements OR lytic or mixed (lytic + sclerotic) bone lesions in the absence of measurable disease as defined above; NOTE: patients with sclerotic / osteoblastic bone lesions only in the absence of measurable disease are not eligible)
• ECOG performance status of 0 - 1
• Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating study treatment. Surgery for placement of vascular access devices is acceptable.
• Female patients of childbearing potential and their partners (if male) and male patients with female partners of childbearing potential and their partners must agree to use a highly effective form of contraception for the duration of the study and until 35 days after the final dose of ADI-PEG 20 or 180 days after the final dose of atezolizumab, pemetrexed or carboplatin, whichever is later.
• Negative serum or urine pregnancy test for female patients of childbearing potential within 14 days prior to cycle 1 day 1.
• Adequate normal organ, marrow and coagulation function within 28 days prior to cycle 1 day 1
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow up.

You may not qualify if:

• Radiotherapy (including for palliative reasons) or targeted therapywithin four weeks before study treatment.
• History of autoimmune disease
• Ongoing toxic manifestations of previous treatments.
• Symptomatic brain or spinal cord metastases (patients must be stable for \> 3 months post radiotherapy or surgery).
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior to the first dose of study treatment.
• Known to be serologically positive for human immunodeficiency virus (HIV).
• Known active hepatitis infection (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Uncontrolled serious intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, and social situations that would limit compliance with study requirements.
• Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within 8 weeks of study treatment.
• Ongoing therapeutic anticoagulation (prophylactic dose low molecular weight heparin is acceptable).
• Concurrent treatment with other experimental drugs or participation in another interventional clinical study with therapeutic intent within 28 days from cycle 1 day 1. Participation in an observational or biomarker study would be acceptable, with prior Sponsor approval.
• Malignancies other than NSCLC within 5 years prior to study entry, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome.
• Prior treatment with cluster of differentiation 137 (CD137) agonists, anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Polaris Group: collaborator
• Hoffmann-La Roche: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Pemetrexed; Carboplatin; ADI PEG20

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Officials

• Peter Szlosarek

  Queen Mary University of London

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 13, 2018
• Study Start: June 1, 2018
• Primary Completion: January 31, 2020
• Study Completion: December 31, 2021
• Last Updated: February 25, 2020

Record last verified: 2020-02