Non Small Cell Lung Cancer Trial of Durvalumab and Tremelimumab in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Disease.

NCT03994393 | Unknown Phase 2 DMC

• 2 other identifiers: CTC 0209ALTG 16/009
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 16

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).

Conditions

EGFR Mutant Advanced Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective tumour response rate (OTRR) and Objective tumour response (OTR)

  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.

  36 months post enrolment of first participant.

Secondary Outcomes (6)

• 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.

• Progression-free survival (PFS)

  36 months post enrolment of first participant.

• Progression-free survival at 12 months (PFS12)

  12 months post enrolment of last participant.

• Overall survival (OS)

  36 months from enrolment of first participant.

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

Participants with no evidence of T790M

Drug: Tremelimumab; Drug: Durvalumab

Cohort 2

ACTIVE COMPARATOR

Participants with evidence of T790M

Drug: Tremelimumab; Drug: Durvalumab

Interventions

Tremelimumab DRUG

During induction, patients will receive 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 (or carboplatin AUC 5 if cisplatin is contra-indicated), and pemetrexed 500mg/m2 via intravenous infusion every 3 weeks. Followed immediately by a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks via intravenous infusion until disease progression or intolerance.

Cohort 1; Cohort 2

Durvalumab DRUG

During induction, patients will receive 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 (or carboplatin AUC 5 if cisplatin is contra-indicated), and pemetrexed 500mg/m2 via intravenous infusion every 3 weeks. Followed immediately by a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks via intravenous infusion until disease progression or intolerance.

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• 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)
• Haemoglobin equal to or greater than 90 x g/L
• Adequate liver function (within 14 days prior to registration and with values within the ranges specified below):
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) equal to or less than 2.5 x institutional upper limit of normal (ULN). (or equal to or less than 5 x ULN if liver metastases are present)
• Bilirubin equal to or less than 1.5 x ULN
• Adequate renal function (within 14 days prior to registration):

You may not qualify if:

• 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.
• 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.
• History of pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.
• History of active primary immunodeficiency or allogeneic transplant.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy

Sponsors & Collaborators

• University of Sydney: lead
• AstraZeneca: collaborator
• Australasian Lung Cancer Trials Group: collaborator

Study Sites (16)

St George Hospital

Kogarah, New South Wales, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, Australia

Location

Monash Medical Centre - Clayton

Clayton, Victoria, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Location

St Vincent's Hospital (Melbourne)

Melbourne, Victoria, Australia

Location

Taiwan Dalin Tzu Chi Hospital

Chiayi City, Taiwan

Location

Taiwan China Medical University Hospital

Taichung, Taiwan

Location

Taiwan Taichung Veterans General Hospital

Taichung, Taiwan

Location

Taiwan National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taiwan Taipei Veterans General Hospital

Taipei, Taiwan

Location

Taiwan Tri-Service General Hospital

Taipei, Taiwan

Location

Related Publications (1)

• Lee CK, Liao BC, Subramaniam S, Chiu CH, Mersiades AJ, Ho CC, Brown C, Lai CL, Hughes BGM, Yang TY, O'Byrne K, Luo YH, Yip S, Ho CL, Bray V, Su WC, Moore M, Feng WL, Bai YY, Ford K, Cummins MM, Stockler MR, Solomon BJ, John T, Chih-Hsin Yang J. Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation-Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE). JTO Clin Res Rep. 2024 Nov 22;6(2):100771. doi: 10.1016/j.jtocrr.2024.100771. eCollection 2025 Feb.

  PMID: 39877028 DERIVED

MeSH Terms

Interventions

tremelimumab; durvalumab

Study Officials

• Chee K Lee

  St George Hospital, Australia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: June 21, 2019
• Study Start: October 23, 2018
• Primary Completion: June 30, 2023
• Study Completion: January 31, 2024
• Last Updated: April 21, 2023

Record last verified: 2023-04

Locations

TW (7); AU (9)