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Attend this session at the
2019 ASCO Annual Meeting!


Session: Lung Cancer—Non-Small Cell Metastatic

Type: Poster Session

Time: Sunday June 2, 8:00 AM to 11:00 AM

Location: Hall A

Phase 1 dose-expansion study of pegylated arginine deiminase, cisplatin, and pemetrexed in patients with argininosuccinate synthetase 1 (ASS1)–deficient non-squamous non-small cell lung cancer.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
9097

Poster Board Number:
Poster Session (Board #420)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 9097)

Author(s): Akhila Ganeshi Wimalasingham, Melissa Mary Phillips, Louise Lim, Sukaina Rashid, Peter Edward Hall, Ramsay Khadeir, Jeremy P. C. Steele, John Conibear, Xiaoxing Feng, Stephen Ellis, Pui Ying Chan, Jim Thomson, Amanda L. Johnston, John S. Bomalaski, Simon Pacey, Michael Sheaff, Peter Wojciech Szlosarek; Barts Health NHS Trust, London, United Kingdom; Barts Cancer Institute, London, United Kingdom; Queen Mary University London, London, United Kingdom; St. Bartholomews' Hospital, London, United Kingdom; St Bartholomew's Hospital, London, United Kingdom; Washington State Univ, Pullman, WA; Barts Health Trust, London, United Kingdom; Polaris Pharmaceuticals Inc., San Diego, CA; Agouron/Pfizer, San Diego, CA; University of Cambridge, Cambridge, United Kingdom

Abstract Disclosures

Abstract:

Background: Pegylated arginine deiminase (ADI-PEG20) targets ASS1-ve tumors, including non–small-cell lung cancer (NSCLC), by potentiating pemetrexed cytotoxicity via arginine depletion. In Beddowes et al (JCO 2017) we showed a 100% disease control rate in thoracic cancers treated with ADI-PEG20, cisplatin and pemetrexed (ADIPemCis). Thus, we tested ADIPemCis in a phase I dose-expansion cohort study of patients (pts) with non-squamous NSCLC. Methods: Good performance (ECOG 0-1) advanced non-squamous NSCLC pts were enrolled at the maximum tolerated dose (MTD) of ADIPemCis, using tumoral ASS1 loss as a selection biomarker. Pem (500mg/m2) and Cis (75mg/m2) were given every 3 weeks with weekly IM ADI-PEG20 (36mg/m2) for up to 4 cycles with maintenance ADI-PEG20 or Pem in responding pts. Primary endpoint was tumor response rate (RR by RECIST 1.1), with secondary endpoints including progression-free survival (PFS), overall survival (OS), and toxicity. We also measured plasma [arginine] and [citrulline], anti-ADI-PEG20 antibodies, and PD-L1 expression. Results: 21 of 70 screened pts (median age 60.1) were enrolled between April 15 and August 17. A confirmed partial response (PR) was observed in 55.6 % (n = 10/18 evaluable pts). Median PFS and OS were 4 months (95% CI 2.9-4.8) and 7.2 months (95% CI 5.1-18.4), respectively. 9% (n = 2/21) remain alive on subsequent therapies. 43% (n = 9/21) experienced grade 3/4 treatment-related toxicities, commonly non-febrile neutropenia. Plasma [arginine] declined rapidly and [citrulline] increased; both changes persisted at 16 weeks. 55% of pts’ tumors (n = 6/11 ) were PD-L1 < 1% by immunohistochemistry. Conclusions: The ADIPemCis regimen is active and safe in ASS1-ve NSCLC pts almost doubling the expected RR. However, the short survival compared with ASS1-agnostic historical controls indicates that ASS1 (and frequent PD-L1) loss selects for a biologically more aggressive and immunorefractory NSCLC phenotype. The iTRAP study opening Q2 of 2019 will assess the safety and tolerability of ADIPemPlatinum(Carbo) with atezolizumab in pts with ASS1-deficient non-squamous NSCLC. Clinical trial information: NCT02029690

 
Other Abstracts in this Sub-Category:

 

1. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 102 First Author: Ferdinandos Skoulidis
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

2. Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 110 First Author: Sean Khozin
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

3. RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 9000 First Author: Kazuhiko Nakagawa
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

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