A Phase 2 Trial of Durvalumab (MEDI4736) and Tremelimumab With Chemotherapy in Metastatic EGFR Mutant Non-squamous Non-small Cell Lung Cancer (NSCLC) Following Progression on EGFR Tyrosine Kinase Inhibitors (TKIs)
Overview
- Phase
- Phase 2
- Intervention
- Tremelimumab
- Conditions
- EGFR Mutant Advanced Non Small Cell Lung Cancer
- Sponsor
- University of Sydney
- Enrollment
- 100
- Locations
- 16
- Primary Endpoint
- Objective tumour response rate (OTRR) and Objective tumour response (OTR)
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The primary purpose of this trial is to evaluate the efficacy and tolerability of durvalumab and tremelimumab with platinum-pemetrexed in patients with metastatic NSCLC (T790+ve or T790M-ve) following progression on EGFR Tyrosine Kinase Inhibitors..
Study population:
Individuals may be eligible to enrol in this trial if aged 18 or over and have been diagnosed with advanced non-small cell lung cancer (T790+ve or T790M-ve) following progression on EGFR Tyrosine Kinase Inhibitors.
Study details:
All participants enrolled in this trial will begin with induction therapy which involves 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 or carboplatin AUC 5, and pemetrexed 500mg/m2 intravenously every 3 weeks.
Participants will then move into a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks until disease progression or unacceptable side effects.
All patients will be reviewed every three to four weeks by blood samples, CT scans and side effect assessments.
It is hoped that the findings from this trial will provide information on whether treatment with durvalumab and tremelimumab with platinum-pemetrexed is feasible, safe and effective for the treatment of advanced non-small cell lung cancer (T790+ve or T790M-ve).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adults, aged 18 years and older with histologically and/or cytologically confirmed non-squamous non-small cell lung cancer with EGFR mutation of Exon 19 deletion or Exon 21 L858R point mutation.
- •Patients with co-mutations are allowed as long as one of the mutation is either Exon 19 deletion or Exon 21 L858R point mutation
- •Patients with mixed histology must have non-squamous NSCLC as the predominant histology.
- •Disease that has progressed and either:
- •(i) No evidence of EGFR T790M resistance mutation in both tissue re-biopsy and plasma after one-line of EGFR tyrosine kinase inhibitor therapy (TKI) OR (ii) T790M mutation (detected in tissue re-biopsy, plasma or both) and progression on 3rd generation EGFR TKI; patients are allowed to have one prior line of TKI therapy before 3rd generation TKI
- •Measurable disease according to RECIST 1.1
- •ECOG performance status of 0 or 1
- •Adequate bone marrow function as defined below (within 14 days prior to registration and with values within the ranges specified below):
- •Platelets equal to or greater than 100 x 109/L
- •Absolute neutrophil count (ANC) equal to or greater than 1.0 x 109/L (equal to or greater than 1000 per mm3)
Exclusion Criteria
- •Prior chemotherapy or immunotherapy, including prior anti-PD-1/anti-PD-L1 or anti-CTLA-4 antibodies, for advanced NSCLC.
- •For recurrent, incurable disease, prior adjuvant chemotherapy or concurrent chemotherapy and radiotherapy with curative intent is allowed, but must have been completed more than 6 months ago, and must not have included treatment with an immune checkpoint inhibitor.
- •Prior EGFR-TKI (e.g. erlotinib, gefitinib, afatinib or osimertinib), including experimental TKI agents, within 8 days or approximately 5 x half-life, whichever is the longer, of the first dose of study treatment is allowed. (If sufficient washout time has not occurred due to schedule or PK properties, an alternative appropriate washout time based on known duration and time to reversibility of drug related adverse events could be agreed upon by contacting the ILLUMINATE Study Team).
- •Mixed histology with any small cell or squamous component.
- •Life expectancy of less than 3 months.
- •Current enrolment or participation in another clinical study with an investigational product during the last 12 months, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study must first be discussed with ILLUMINATE Study Team before study enrolment.
- •Any unresolved toxicity NCI CTCAE equal to or greater than Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
- •Patients with equal to or greater than Grade 2 neuropathy will be evaluated on a case-by-case basis after consultation with the ILLUMINATE Study Team.
- •Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the ILLUMINATE Study Team.
- •Radiotherapy or major surgery (as defined by the local investigator) within 4 weeks of the first dose of study drug. Note: Local surgery on isolated lesions for palliative intent is acceptable.
Arms & Interventions
Cohort 1
Participants with no evidence of T790M
Intervention: Tremelimumab
Cohort 1
Participants with no evidence of T790M
Intervention: Durvalumab
Cohort 2
Participants with evidence of T790M
Intervention: Tremelimumab
Cohort 2
Participants with evidence of T790M
Intervention: Durvalumab
Outcomes
Primary Outcomes
Objective tumour response rate (OTRR) and Objective tumour response (OTR)
Time Frame: 36 months post enrolment of first participant.
Objective tumour response rate (OTRR) as defined by RECIST 1.1. Objective tumour response (OTR) is defined as a partial response or compete response by RECIST 1.1. OTRR is defined as the proportion (percentage) of participants with a confirmed CR or PR according to RECIST 1.1.
Secondary Outcomes
- Progression-free survival at 12 months (PFS12)(12 months post enrolment of last participant.)
- Number and Severity (assessed as a composite) of Adverse Events(36 months post enrolment of first participant.)
- Disease control (Disease Control Rate (DCR)(36 months post enrolment of first participant.)
- Objective tumour response rate (OTRR) & Objective tumour response (OTR)(36 months post enrolment of first participant.)
- Overall survival (OS)(36 months from enrolment of first participant.)
- Progression-free survival (PFS)(36 months post enrolment of first participant.)