Data were reported from across AstraZeneca’s industry-leading lung cancer portfolio at the World Conference on Lung Cancer ( WCLC ) 2015, in Denver, Colorado ( U.S. ). 25 abstracts ( including 9 oral and 4 late breaker presentations ) on the company’s lung cancer pipeline, designed to address the unmet needs of patients with different forms of lung cancer, were presented.
A) AZD92911: targeting resistance mechanisms in lung cancer
AZD9291 was the focus of six oral presentations on its clinical activity in both first-line and previously-treated patients with epidermal growth factor receptor mutation ( EGFRm ) T790M advanced non-small cell lung cancer ( NSCLC ). The data are consistent with previously reported efficacy and safety results of AZD9291 in these treatment settings.
AZD9291 was recently granted US Priority Review designation in recognition of its potential to target the mutation that drives resistance to current treatments for EGFR mutation positive advanced non-small cell lung cancer in the majority of patients.
In addition to AZD9291, AstraZeneca has also presented results from the Gefitinib ( Iressa ) Clinical Access Programme ( ICAP ), which provides data on the long-term safety and tolerability of the EGFR tyrosine kinase inhibitor in 188 US cancer patients outside the clinical trial setting.
Iressa was approved by the US Food and Drug Administration ( FDA ) as a first-line treatment for EGFRm metastatic NSCLC in July 2015, and is already available in 91 countries worldwide.
B) Immuno-oncology: update on key clinical trials
Trial designs for the ongoing immuno-oncology late-stage studies presented at WCLC include:
ATLANTIC: a phase II trial of Durvalumab ( PD-L1 mAb ) as third-line treatment in patients with PD-L1 positive, locally advanced or metastatic NSCLC;
ARCTIC: a phase III trial of Durvalumab monotherapy and in combination with Tremelimumab ( CTLA-4 mAb ) versus standard of care in third-line metastatic NSCLC;
PACIFIC: a phase III placebo-controlled trial of Durvalumab compared to placebo in patients with locally advanced, unresectable, NSCLC following completion of treatment with chemoradiotherapy and no evidence of tumour progression.
The FDA has granted Fast Track designation to Tremelimumab for the treatment of mesothelioma, an aggressive, rare form of cancer that affects the lining of the lungs and abdomen.
Durvalumab was also granted Fast Track designation for patients with advanced NSCLC, who have received at least two prior systemic-treatment regimens, who do not have EGFR mutations or anaplastic lymphoma kinase ( ALK ) alterations, and have tumours that are determined to be PD-L1 positive.
C) Pivotal studies in lung cancer
Data presented at WCLC are part of AstraZeneca’s lung cancer programme, which includes the following pivotal clinical trials and upcoming milestones.
ATLANTIC / Durvalumab, third line - A phase II trial in third-line metastatic NSCLC assesses the efficacy of Durvalumab in tumours that are PD-L1 positive in patients with locally advanced or metastatic NSCLC who have received two or more prior systemic treatments. Ongoing ( recruitment completed for certain cohorts ). Data to be presented in 2016.
ARCTIC / Durvalumab, third line - The phase III trial in third-line metastatic NSCLC is recruiting patients and contains a randomised Durvalumab monotherapy sub-study for PD-L1 positive tumours versus standard of care ( SoC ) and a sub-study with a concurrent-combination treatment with Tremelimumab versus the contribution of components and SoC in patients with PD-L1 negative tumours. Currently recruiting.
MYSTIC / Durvalumab, Tremelimumab, first line - A phase III Durvalumab - Tremelimumab trial in first-line metastatic NSCLC, which is recruiting in PD-L1 unselected, EGFR/ALK wild-type patients and includes a sub-group analysis of PD-L1 positive and PD-L1 low/negative tumours. The primary endpoint is progression free survival ( PFS ) and the trial includes Durvalumab monotherapy and the Durvalumab - Tremelimumab combination versus standard of care. Currently recruiting.
NEPTUNE / Durvalumab, Tremelimumab, first line - A further phase III Durvalumab - Tremelimumab study in the first-line metastatic NSCLC setting, versus standard of care with overall survival ( OS ) as the primary endpoint; complements the MYSTIC PFS trial. To be initiated
Name to be announced / Durvalumab, first line - A third first-line Phase III NSCLC trial of Durvalumab plus chemotherapy in PD-L1 unselected, EGFR/ALK wild-type NSCLC. To be initiated.
PACIFIC / Durvalumab, stage III unresectable - A phase III trial assessing the progression free survival and overall survival with Durvalumab compared to placebo in patients with locally advanced, unresectable, NSCLC following completion of treatment with chemoradiotherapy and no evidence of tumour progression. Currently recruiting.
AURA / AZD9291, first line, second line and beyond - PhaseI/II openlabel, dose escalation and expansion cohort study to investigate the safety and tolerability,pharmacokinetics and response to therapy of AZD9291in patients with advanced NSCLC who had disease progression following treatment with an approved EGFR TKI. Completed recruitment; trial ongoing. Phase I data presented at ESMO 2014, ELCC 2015 and ASCO 2015.
AURA2 / AZD9291, second line and beyond - Phase II, open-label, single-arm confirmatory trial to assess the safety and efficacy of AZD9291 in patients with advanced or metastatic NSCLC whose disease has progressed with previous EGFR-TKI therapy and whose tumours harbour an EGFR and T790M mutation. Completed recruitment; trial ongoing.
AURA3 / AZD9291, second line - Phase III, open label, randomised study of AZD9291 versus Platinum-based doublet chemotherapy for patients with locally advanced or metastatic NSCLC whose disease has progressed with previous TKI therapy and with the EGFR and T790M mutation. Currently recruiting.
CAURAL / AZD9291 in combination with Durvalumab, second line and beyond - A phase III, open label, randomised trial to assess the efficacy and safety of AZD9291 in combination with Durvalumab versus AZD9291 monotherapy in patients with locally advanced or metastatic EGFR receptor T790M mutation-positive NSCLC who have received prior EGFR TKI therapy. Currently recruiting.
FLAURA / AZD9291, first line - A phase III, double blind, randomised trial comparing the efficacy and safety of AZD9291 versus standard of care EGFR-TKI treatment ( Gefitinib or Erlotinib ) in treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC. Currently recruiting; trial design presented at ASCO 2015.
TATTON / AZD9291 combinations - A multi-arm, phase Ib trial investigating AZD9291 in combination with Durvalumab, Savolitinib ( MET inhibitor; AZD6094 ) or Selumetinib ( MEK1/2 inhibitor; AZD6244, ARRY-142886 ) in patients with advanced EGFR mutant lung cancer that has progressed on previous EGFR TKI treatment. Currently recruiting; initial trial results presented at ASCO 2015.
SELECT1 / Selumetinib, second line - A phase III, double-blind, randomised, placebo-controlled trial to assess the efficacy and safety of Selumetinib in combination with Docetaxel, in patients receiving second-line treatment for KRAS mutation-positive locally advanced or metastatic NSCLC ( stage IIIB – IV ). Currently recruiting. ( Xagena )
Source: AstraZeneca, 2015