Primary Outcome Measures:
Determine preliminary estimates of efficacy, measured by modified RECIST criteria for MPM and RECIST 1.1 criteria for non-squamous NSCLC, for ADI-PEG 20 in combination with pemetrexed and cisplatin [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
Determine the MTD of ADI-PEG 20 in combination with pemetrexed and cisplatin [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Detailed Description:
Weekly ADI-PEG 20 will be cohort dose escalated (9, 18, and 36 mg/m2), with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 both given every 3 weeks. Subjects may receive a maximum of 6 – 3 week cycles of ADIPemCis for a total of 18 weeks of treatment. Those subjects completing 18 weeks may continue on ADI-PEG 20 monotherapy if they have SD or better.
Eligibility Criteria
- Inclusion Criteria:
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- Histologically proven mesothelioma or non-squamous NSCLC
- Subjects with EGFR mutant NSCLC must have had an EGFR tyrosine kinase inhibitor (TKI) and progressed or been shown to be intolerant of therapy
- Subjects must be treatment naïve to systemic chemotherapy (i.e., ADI-PEG 20 + pemetrexed + cisplatin will be first-line systemic chemotherapy)
- ASS1 deficiency using immunohistochemistry (IHC) demonstrated on tissue biopsy
- ECOG PS 0-1
- Expected survival of at least 3 months
- Age 18 years or over (there is no upper age limit)
- Evaluable disease by modified RECIST criteria for MPM and RECIST 1.1 criteria for non-squamous NSCLC
- Written (signed and dated) informed consent and must be capable of co-operating with treatment and follow up
- Adequate hematologic, hepatic, and renal function
- Exclusion Criteria:
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- Radiotherapy (except for palliative reasons), EGFR, TKI, ALK inhibitor or immunotherapy the previous four weeks before study treatment.
- Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator are stable and with the trial sponsor approval should not exclude the patient
- Symptomatic brain (patients must be stable for > 1 month post radiotherapy or surgery) or spinal cord metastases
- Major thoracic or abdominal surgery from which the patient has not yet recovered
- Therapeutic anticoagulation (prophylactic dose low molecular weight heparin is acceptable).
