Clovis Oncology Research Articles

1484PD - Final PFS, updated OS and safety data from the randomised, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC

BackgroundWe report mature PFS, updated OS and safety data from the global phase III ALEX study (NCT02075840) of ALC vs CRZ in patients (pts) with untreated ALK+ NSCLC after a further 12 months (m) of follow-up (cutoff date: 30 Nov 2018). MethodsEligible pts had stage IIIB/IV ALK+ NSCLC (by central IHC), ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC. Asymptomatic CNS metastases (mets) were allowed. Pts were randomised 1:1 to twice-daily ALC 600mg (n=152) or CRZ 250mg (n=151). Primary endpoint: investigator (INV)-assessed PFS (RECIST v1.1), with q8w CNS imaging in all pts. ResultsMature, median INV-assessed PFS: 34.8 m (95% CI 17.7–NR) ALC vs 10.9 m (95% CI 9.1–12.9) CRZ (ITT stratified HR 0.43, 95% CI 0.32–0.58; p<0.0001); pts with event, 53.3% ALC vs 80.8% CRZ. Median duration of follow-up: 37.8 m ALC vs 23.0 m CRZ. Median INV-assessed PFS was longer with ALC vs CRZ in pts with baseline (BL) CNS mets (25.4 m vs 7.4 m, respectively, HR 0.37, 95% CI 0.23–0.58) and in those without (38.6 m vs 14.8 m, respectively, HR 0.46, 95% CI 0.31–0.68). PFS event-free rate was higher with ALC vs CRZ regardless of BL CNS mets status, with 43.7% of ALC pts event-free at 4 years (Table). OS data remain immature (events: 32%; stratified HR 0.69, 95% CI 0.47–1.02). OS in pts with CNS mets at BL, HR 0.60 (95% CI 0.34–1.05) and in pts without CNS mets at BL, HR 0.77 (95% CI 0.45–1.32). The 4-year OS rate was 64.5% (95% CI 55.6–73.4) with ALC vs 52.2% (95% CI 42.6–64.8) with CRZ. Despite longer median treatment duration with ALC vs CRZ (27.7 m vs 10.8 m), the safety profile for ALC remains favourable; fewer ALC-treated pts experienced grade 3–5 AEs (48.7% vs 55.0% CRZ). ConclusionsThis final updated PFS analysis confirms the superior efficacy and favourable tolerability of ALC compared with CRZ in pts with untreated ALK+ NSCLC. OS data remain immature (stratified HR 0.69, 95% CI 0.47–1.02), with a 4-year OS rate of 64.5% (95% CI 55.6–73.4) with ALC.Table1484PDTablePFS event-free rate, % (95% CI)OS event-free rate, % (95% CI)ALC (n=152)CRZ (n=151)ALC (n=152)CRZ (n=151)Duration (years)OverallBaseline CNS metsOverallBaseline CNS metsOverallOverallYesNoYesNo167.8 (60.3–75.3)58.574.548.0 (39.7–56.2)32.557.284.3 (78.4–90.2)82.5 (76.1–88.9)256.6 (48.6–64.6)52.059.824.8 (17.6–32.1)6.335.772.5 (65.1–79.9)65.1 (56.7–73.4)346.4 (38.2–54.5)40.550.613.5 (7.7–19.3)2.120.266.9 (59.0–74.8)56.7 (47.8–65.6)443.7 (35.4–51.9)38.047.6NE (NE–NE)NENE64.5 (55.6–73.4)52.2 (42.6–61.8)NE, not estimable Clinical trial identificationNCT02075840. Editorial acknowledgementNicola Griffin of Gardiner-Caldwell Communications; funded by F. Hoffmann-La Roche. Legal entity responsible for the studyF. Hoffmann-La Roche Ltd. FundingF. Hoffmann-La Roche Ltd. DisclosureT.S.K. Mok: Leadership role: Sanonics Ltd.; Honoraria (self), Advisory / Consultancy: ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chimed, Cirina, Fishawack Facilitate, Ignyta, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, SFJ Pharm; Research grant / Funding (self): AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, SFJ Pharmaceutical and XCovery. A.T. Shaw: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Genentech, Pfizer, Novartis, Ariad, Ignyta, Daiichi-Sankyo, Taiho, Blueprint medicines, LOXO, EMD Serono and Foundation medicine. R.D. Camidge: Honoraria (self), Advisory / Consultancy: AbbVie, Ariad, Array, Celgene, Clovis Oncology, Eli Lilly, Genoptix, G1 Therapeutics, Novartis, Orion, and F. Hoffmann-La Roche Ltd/Genentech. S.M. Gadgeel: Honoraria (self), Advisory / Consultancy: Ariad, AstraZeneca, Bristol-Myers Squibb, Pfizer and F. Hoffmann-La Roche Ltd/Genentech. R. Dziadziuszko: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro. D. Kim: Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro; Travel / Accommodation / Expenses: Novartis Oncology; Research grant / Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan. M. Perol: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Sharp & Dohme, Chugai, Bristol-Myers Squibb, Amgen, Novartis, Pierre Fabre, AstraZeneca, Takeda ; Research grant / Funding (institution): F. Hoffmann-La Roche Ltd, AstraZeneca, Chugai and Takeda. S. Ou: Honoraria (self): ARIAD, AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd/Genentech and TP Therapeutics; Speaker Bureau / Expert testimony: ARIAD, AstraZeneca and F. Hoffmann-La Roche Ltd/Genentech; Research grant / Funding (self): ARIAD, AstraZeneca, Daiichi Sankyo, Pfizer and F. Hoffmann-La Roche Ltd/Genentech; Shareholder / Stockholder / Stock options: TP Therapeutics. W. Bordogna: Full / Part-time employment: F. Hoffmann-La Roche Ltd. V. Smoljanović: Full / Part-time employment: F. Hoffmann-La Roche Ltd. M. Hilton: Full / Part-time employment: F. Hoffmann-La Roche Ltd. S. Peters: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche Ltd, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Nova. All other authors have declared no conflicts of interest.

923P - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors

923P - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors

880P - Impact of treatment sequence in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Data from the prospective PROREPAIR-B study

880P - Impact of treatment sequence in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Data from the prospective PROREPAIR-B study

LBA1 - Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study)

LBA1 - Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study)

1190PD - Phase II study of olaparib + durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC)

BackgroundOlaparib (Lynparza®) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved as maintenance treatment of PSR OC. MEDIOLA assessed olaparib in combination with the anti-programmed cell death ligand1 antibody, durvalumab, in germline BRCA1 and/or BRCA2 mutated (gBRCAm) PSR OC (NCT02734004). The 12-week (wk) disease control rate (DCR) = complete response [CR] + partial response + stable disease) was presented at SGO 2018 (late-breaker abst. 4). MethodsPts had PSR OC, gBRCA1 or gBRCA2 mutation, and had received at least one prior line of platinum. Pts received olaparib 300mg PO BID for a 4-wk runin, then olaparib 300mg PO BID and durvalumab 1.5g IV q 4 wks until progressive disease. Tumours were assessed by RECIST 1.1 at baseline, 4 wks, then every 8 wks. Primary endpoints were 12wk DCR and safety. Secondary endpoints were 28-wk DCR, objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and biomarker analyses. ResultsThirty-two/thirty-four pts treated were eligible. With the data cut-off on 1 Nov 2018, 28% pts were still on treatment. Most common ≥Grade 3 AEs were anaemia (17.6%), elevated lipase (11.8%), neutropenia (8.8%), and lymphopenia (8.8%). Five pts discontinued olaparib and three discontinued durvalumab due to an adverse event. The 28-wk DCR was 65.6% (90% CI: 49.6%, 79.4%). ORR was 71.9% (95% CI: 53.25%, 86.25%) with a total of seven CRs. Median PFS was 11.1 months (95% CI: 8.2, 15.9) with a median DoR of 10.2 months (25/75th percentile: 5.6, NC). Second-line pts (N=13, 40.6%) had not yet reached the medians for PFS or DoR. Median OS for all pts was not yet reached, with 87.0% of pts alive at 24 months (median follow up=20.4 months). Updated results will be presented. ConclusionsThe combination of olaparib and durvalumab was well tolerated and showed promising median PFS and DoR. Median PFS and DoR for pts with fewer prior lines of chemotherapy was not yet reached, suggesting that these pts may derive a greater benefit from the combination. The CR rate was higher than anticipated. This cohort has been expanded to further explore the durability of this chemotherapy-sparing combination. Clinical trial identificationNCT02734004. Editorial acknowledgementEmma Robinson, Mudskipper Business, Ltd, funded by AstraZeneca. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureY. Drew: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Tesaro ; Advisory / Consultancy: Genmab; Research grant / Funding (institution): Oncology; Research grant / Funding (institution): Veratsem. B. Kaufman: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Medison. S. Banerjee: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. P. Roxburgh: Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro. R.H. Alvarez: Honoraria (self): Eisai; Honoraria (self): Puma; Leadership role: Cancer Treatment Center of America. S. Domchek: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Clovis Oncology; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): PharmaMar. C. Gresty: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H.K. Angell: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. V. Rocher Ros: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. K. Meyer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Lanasa: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Herbolsheimer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.

940P - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)

940P - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)

877P - Serum biomarkers of bone metabolism in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with radium-223 (Ra223): Results from a prospective multicentre study

BackgroundRa223 is a life-prolonging alpha-emitter bone targeted therapy for mCRPC patients with bone metastases. However, evidence on biomarkers that may help us in patient selection are lacking. Total ALP (tALP) appeared to be a potential marker of Ra223 effect in early studies (Sartor, Ann Oncol, 2017). Other bone-related markers, as bone-specific ALP (BALP), have demonstrated its prognostic value in mCRPC patients with bone metastases (Fizazi K, Eur Urol, 2015; Lara PN, J Natl Cancer Inst, 2014). MethodsPRORADIUM (NCT022925702) is a prospective multicentre cohort study in mCRPC patients treated with Ra223. The primary aim was to assess the impact of baseline serum biomarkers of bone formation (BALP and C-terminal of type 1 collagen propeptide [CICP]) on overall survival (OS). Secondary aims include the correlation of progression-free survival (PFS), time to PSA progression (TTPP) and skeletal-related events free-survival (SRE-FS) with serum bone markers. Results142 out of 168 pts enrolled in the study were included in this preliminary analysis. Median age was 74 yrs, 85.5% pts had ECOG 0-1, 52% pts completed 5-6 cycles of Ra223. Higher baseline levels of BALP and CICP were associated to number of metastases in bone-scan (p=0.007 and p=0.016, respectively) and baseline pain (p=0.014 and p=0.050, respectively). After a median follow-up of 18 months, 91 deaths were observed, with a median OS of 11.5 months (95%CI: 9.1-13.9). Patients with baseline BALP and CICP values above the median showed a trend to shorter TTPP (BALP: 2.8 vs 3.1 m, p=0.016; CICP: 2.8 vs 3.0 m, p=0.091) and PFS (BALP: 4.4 vs 5.1 m, p=0.070; CICP: 4.2 vs 5.5 m, p=0.281), respectively. The elevation of bone markers above the median was significantly associated with worse OS (BALP: 8.8 vs 17.9 m, p<0.001; CICP: 9.4 vs 16.8 m, p=0.001). There were not associations found with SRE-FS. ConclusionsOur results suggest that baseline serum markers of bone formation may serve as biomarkers for prognosis in mCRPC patients treated with Ra233. Clinical trial identificationNCT022925702. Legal entity responsible for the studyIBIMA and CNIO. FundingBayer, CRIS Cancer Foundation, Grant from Instituto de Salud Carlos III (PI16/01565). DisclosureN. Romero Laorden: Honoraria (self), Travel / Accommodation / Expenses: Bayer, Astellas Pharma, Janssen-Cilag, Sanofi-Aventis, PharmaMar, MSD, Roche. R. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. E. Almagro Casado: Honoraria (self): MSD; Travel / Accommodation / Expenses: BMS. E. Gonzalez Billalabeitia: Travel / Accommodation / Expenses: BMS, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi. A. Montesa: Advisory / Consultancy: Janssen-Cilag, Pfizer, Sanofi, Astellas Pharma; Travel / Accommodation / Expenses: Pfizer. G.A. De Velasco Oria de Rueda: Honoraria (self), Advisory / Consultancy: Pfizer, Novartis, Ipsen, Astellas Pharma, BMS, Bayer, MSD, Roche. R. Morales Barrera: Honoraria (self): MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Advisory / Consultancy: MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Speaker Bureau / Expert testimony: MSD, Sanofi, AstraZeneca, Asofarma, Janssen; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, INC, Astellas Pharma, AstraZeneca, Aveo Pharmaceuticals, Bayer, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim España, BMS, Clovis Oncology, Cougar Technology, Deciphera Pharmaceuticals LL; Travel / Accommodation / Expenses: MSD, Roche, Lilly, Clovis Oncology, Bayer, Janssen-Cilag, Astellas Pharma, AstraZeneca. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer, Genentech, Roche, Pfizer, Astellas Medivation, Tokai Pharmaceuticals; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. D. Olmos Hidalgo: Honoraria (self): Janssen-Cilag, Bayer, Sanofi; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Bayer, Janssen, AstraZeneca, Roche/Genentech, Medivation/Pfizer, Astellas, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. All other authors have declared no conflicts of interest.

990TiP - Phase III LEAP-011 trial: First-line pembrolizumab with lenvatinib in patients with advanced urothelial carcinoma ineligible to receive platinum-based chemotherapy

990TiP - Phase III LEAP-011 trial: First-line pembrolizumab with lenvatinib in patients with advanced urothelial carcinoma ineligible to receive platinum-based chemotherapy

902O - An adaptive, biomarker directed platform study in metastatic urothelial cancer (BISCAY) with durvalumab in combination with targeted therapies

902O - An adaptive, biomarker directed platform study in metastatic urothelial cancer (BISCAY) with durvalumab in combination with targeted therapies

1543P - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase II ALTA trial

1543P - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase II ALTA trial

883P - Androgen receptor (AR) aberrations in patients (Pts) with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) plus androgen deprivation therapy (ADT) in TITAN

883P - Androgen receptor (AR) aberrations in patients (Pts) with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) plus androgen deprivation therapy (ADT) in TITAN

851PD - Patient-reported outcomes (PROs) from TITAN: A phase III, randomized, double-blind study of apalutamide (APA) versus placebo (PBO) added to androgen deprivation therapy (ADT) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC)

851PD - Patient-reported outcomes (PROs) from TITAN: A phase III, randomized, double-blind study of apalutamide (APA) versus placebo (PBO) added to androgen deprivation therapy (ADT) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC)

855PD - Docetaxel for hormone-naïve prostate cancer (PCa): Results from long-term follow-up of non-metastatic (M0) patients in the STAMPEDE randomised trial

855PD - Docetaxel for hormone-naïve prostate cancer (PCa): Results from long-term follow-up of non-metastatic (M0) patients in the STAMPEDE randomised trial

862P - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE

BackgroundDocetaxel (Doc) was initially licenced for CRPC (TAX327) but more recently trials showed Doc at HSPC diagnosis improved survival, shifting patterns of use. Higher neutropenic toxicity rates were reported in the HSPC trials, but it is unclear if this was due to the Doc timing or differences in case-mix. We compared sepsis rates for Doc at HSPC and CRPC using routine NHS data for men randomised in STAMPEDE in England. MethodsSTAMPEDE patient data were linked to routine NHS data (Hospital Episode Statistics: HES; Systemic Anti-Cancer Therapy: SACT). Patient note review (ref) linked to NHS data assessed admission rates by HSPC & CRPC Doc at 1 site (N=44) and were used to develop and validate algorithms for detecting sepsis events across the entire data set. Algorithms were restricted to sepsis-only & sepsis + neutropenia (S+N) (N=3645). Missing HES CRPC Doc regimens were imputed with HES (N=3645) or enhanced with SACT (N=1573). Odds ratios (OR) were calculated for risk of sepsis (OR<1 = lower risk for HSPC). ResultsSepsis rates varied by method; for most, rates at CRPC were higher than in TAX327 but similar to or higher than reported STAMPEDE HSPC data.Table862PTableHSPC Sepsis/PtsCRPC Sepsis/Pts% diffOR, 95% CIN%N%Ref2/15136/2227-140.4 (0.1 - 2.1)HESSepsis69/8348114/118310-20.9 (0.6 - 1.2)S+N134/83416148/11831331.3 (1.0 - 1.6)Imputed134/83416489/135136-200.4 (0.4 - 0.6)+ SACT41/2002160/2972011.0 (0.7 - 1.6) ConclusionsThis analysis does not support the hypothesis that HSPC Doc has a higher sepsis risk than Doc use in CRPC. Sepsis rates found using routine data were higher than in the TAX327 trial but similar to reported “real world” CRPC data. Rates varied by data-identification method used; for most, CRPC sepsis rates were higher or similar to HSPC rates & overall a little higher than the reported STAMPEDE HSPC rate. These data suggest CRPC Doc has a similar or higher sepsis rate than use in HSPC & this should be factored into discussions for men with newly-diagnosed metastatic HSPC and supports Doc use in this setting. Legal entity responsible for the studyThe STAMPEDE Trial Group. FundingUniversity of Warwick, Warwick Medical School (HM PhD studentship). DisclosureM.K.B. Parmar: Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Clovis oncology; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution), The Unit I am Director of also receives educational grants and other non- financial support from a large number of different companies: Other. P. Patel: Advisory / Consultancy: Roche/Genentech. M.R. Sydes: Honoraria (self): Lilly; Honoraria (self), Research grant / Funding (self): Sanofi; Honoraria (self): Janssen; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Janssen-Cilag; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Novartis; Research grant / Funding (self): Clovis Oncology. N.D. James: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen; Honoraria (self), Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Ferring; Honoraria (self): Oncogenex; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.

889P - Circulating tumour cells (CTC) count and prostate-specific antigen (PSA) response measures in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with docetaxel (Doc)

BackgroundClinically meaningful measures of response are needed in mCRPC. Post-treatment CTC decline have shown to be superior to PSA response in determining outcome in pts treated with AR signalling inhibitors. We compared the performance of CTC and PSA measures of response in mCRPC Doc-treated pts. MethodsBaseline and post-treatment (6 to 9 weeks) CTC of mCRPC pts treated with Doc at first or second-line in a prospective study were determined with CellSearchTM platform. CTC response was defined: 30% decline from baseline (CTC30%), conversion (≥5 to<5; CTCConv) or decline to 0 CTC in pts with >0 baseline CTC (CTC0). PSA response was determined at 12w as 30% (PSA30) or 50% decline (PSA50) from baseline. Cox-regression model were used to evaluate the association of baseline CTC (BLCTC), CTC response and PSA response measures with overall survival (OS), progression-free survival (PFS) or time to PSA progression (TTPP). C-index were used to evaluate the performance of each of the Cox regression model. Results80 pts had evaluable BLCTC, 52 had evaluable post-treatment CTC count. Of 80 eligible pts, 53 (66.3%) received Doc at first-line. Median OS was 19 m (95%CI:16.4-21.8); median BLCTC was 7. BLCTC were associated with bone mts, higher PSA, ALP and LDH, and lower albumin levels. BLCTC was associated with OS (HR: 3.5; p<0.001), PFS (HR: 1.98; p=0.001) and TTPP (HR: 1.8; p=0.001). CTC (CTC30%, CTCConv, CTC0) but not PSA (PSA30, PSA50) response measures were significantly associated with OS. C-index values were higher for CTC resp endpoints (Table). 24 pts had discordant PSA30 and CTC30% response; longer OS (18.4 vs 8.4m; p=0.188) was observed in pts with CTC30% resp, without PSA30 resp.Table889PTableN (%)HR (95%CI); p-valueC-indexCTC Conv27 (51.9)0.33 (0.18-0.60); p<0.0010.665CTC08 (15.4)0.26 (0.10-0.67); p=0.0050.602CTC30%34 (65.4)0.33 (0.18-0.61); p<0.0010.644PSA3032 (61.5)0.72 (0.40-1.30); p=0.2710.563PSA5022 (42.3)0.68 (0.38-1.20); p=0.1830.595 ConclusionsBaseline CTC were associated with OS, PFS and TTPP. CTC response measures were significantly associated with outcome, and showed a greater performance than PSA response measures in mCRPC Doc-treated pts. Legal entity responsible for the studySpanish National Cancer Research Center (CNIO) and The Institute of Cancer Research (ICR). FundingHas not received any funding. DisclosureR. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. N. Romero Laorden: Honoraria (self): MSD, Sanofi-Aventis, Astellas, Janssen-Cilag; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, PharmaMar; Research grant / Funding (institution): Bayer, Astellas, Janssen-Cilag, Sanofi-Aventis. E. Almagro Casado: Honoraria (self): MSD; Travel / Accommodation / Expenses: BMS. M. Saez: Honoraria (self): Bristol-Myers Squibb, Pfizer, Novartis, Bayer, Janssen-Cilag, Sanofi-Aventis, Astellas Pharma, Ipsen, EUSA Pharma; Advisory / Consultancy: Bristol-Myers Squibb, Pfizer, Novartis, Bayer, Janssen-Cilag, Sanofi-Aventis, Astellas Pharma, Ipsen, EUSA Pharma; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, Novartis, Bayer, Janssen-Cilag, Sanofi-Aventis, Astellas Pharma, Ipsen, EUSA Pharma. D. Olmos Hidalgo: Honoraria (self): Janssen-Cilag, Bayer, Sanofi; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Bayer, Janssen-Cilag, AstraZeneca, Roche/Genentech, Medications/Pfizer, Astellas, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. All other authors have declared no conflicts of interest.

LBA81_PR - Phase II/III blood first assay screening trial (BFAST) in patients (pts) with treatment-naïve NSCLC: Initial results from the ALK+ cohort

LBA81_PR - Phase II/III blood first assay screening trial (BFAST) in patients (pts) with treatment-naïve NSCLC: Initial results from the ALK+ cohort

450PD - A phase I study of ATR inhibitor, AZD6738, as monotherapy in advanced solid tumours (PATRIOT part A, B)

BackgroundATR inhibition (ATRi) exploits high levels of replication stress and G1/S cell cycle checkpoint dysfunction frequently seen in cancers, increasing DNA damage and inducing mitotic crisis. ATRi may also potentiate DNA-damaging anticancer therapies to improve clinical activity. MethodsWe present results from the monotherapy phase of a study of AZD6738, an oral ATRi in patients with advanced solid tumours (NCT02223923). Endpoints were MTD, safety, tolerability, pharmacokinetics (PK) and preliminary efficacy. MTD and PK were previously presented. ResultsForty-six patients enrolled and received at least 1 dose AZD6738 to February 2019, 24 completed ≥1 cycle (28 days) of treatment in the dose-escalation phase, 20 commenced treatment in expansion phase, testing 2 different schedules at MTD (160mg BD). The median number of cycles was 3 (range 2-12) in dose-escalation phase and 4 (1-12) in the dose-expansion cohort. 17/26 (65%) patients in dose escalation and 7/20 (35%) in dose-expansion had G≥3 treatment-related adverse events (TRAEs). An intermittent schedule (2-week-on, 2-week-off) was better tolerated than continuous dosing, with G≥3 TRAEs in 4/6 (67%) receiving continuous and 3/15 (20%) with intermittent dosing. The most common TRAEs were fatigue, anaemia, nausea and thrombocytopenia; 20 (77%) of patients in dose escalation and 16 (80%) in expansion discontinued AZD6738 due to progressive disease (PD). 5 (19%) patients in dose-escalation and 1 (5%) in dose-expansion discontinued due to toxicity. Best overall response was confirmed partial response (PR) in 3 (7%) participants, unconfirmed PR in 1 (2%), stable disease (SD) in 22 (48%) and PD in 12 (26%). Early clinical PD or toxicity prevented radiological assessment in 8 (17%). 5/24 (21%) participants in dose-escalation and 5/20 (25%) in dose-expansion had SD of≥4 cycles (16 weeks) duration. ConclusionsAZD6738 is well tolerated at 160mg BD on a 2-week-on, 2-week-off schedule. ATRi monotherapy resulted in confirmed PR and a high proportion of prolonged SD. Future cohorts will enrich for DNA damage response-deficient tumours. A parallel dose-escalation study of AZD6738 combined with palliative radiotherapy is underway. Funding: CRUKD/14/007. Clinical trial identificationNCT02223923; EudraCT: 2013-003994-84. Legal entity responsible for the studyRoyal Marsden NHS Foundation Trust and The Institute of Cancer Research: Royal Cancer Hospital. FundingCancer Research UK, ECMC Combinations Alliance, AstraZeneca. DisclosureS.A. Smith: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. E. Dean: Full / Part-time employment: AstraZeneca. J. Spicer: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self): Lilly; Honoraria (self): Lytix Biopharma; Honoraria (self): Pierre Fabre; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Shionogi; Research grant / Funding (self): GlaxoSmithKline; Research grant / Funding (self): Quintiles; Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: AstraZeneca. M.D. Forster: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharpe & Dohme; Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly. K.J. Harrington: Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca-Medimmune; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Lytix Biopharma; Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dohme; Advisory / Consultancy: Merck; Advisory / Consultancy: Oncos Therapeutics; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Viralytics; Research grant / Funding (self): Oncolytics Biotech. All other authors have declared no conflicts of interest.

1063TiP - ENGOT-EN9/LEAP-001: A phase III, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer

BackgroundWhile early stage endometrial cancer (EC) is associated with a favorable prognosis, prognosis for advanced or recurrent EC is poor. Paclitaxel and carboplatin chemotherapy (CT) is often used as first-line treatment for these patients; however, there exists an imperative need for more effective and tolerable therapies. In KEYNOTE-146, combination therapy with the PD-1 inhibitor pembrolizumab (pembro) and the tyrosine kinase inhibitor lenvatinib resulted in an ORR of 39% in patients with EC (Makker et al. ASCO 2018). Based on these promising data, the ENGOT-EN9/LEAP-001 study was initiated to assess this combination therapy in women with recurrent or advanced EC. Trial designThe ENGOT-EN9/LEAP-001 study (NCT03884101) is a phase 3, randomized, open-label, active-controlled trial comparing combination therapy with pembro and lenvatinib to paclitaxel and carboplatin CT in patients with newly diagnosed stage III-IV or recurrent EC (NCT03884101). Approximately 720 patients not previously treated with systemic chemotherapy (except as part of a chemoradiation regimen), antiangiogenic agents, PD-1 or PD-L1 inhibitors, or other T-cell receptor–targeted agents will be randomized 1:1 to pembro (200mg Q3W) plus lenvatinib (20mg daily) or paclitaxel and carboplatin CT (pac 175mg/m2 plus carb AUC 6 Q3W). Patients will first be stratified by proficient vs deficient mismatch repair status (pMMR vs dMMR), and pMMR patients will be further stratified by ECOG performance status (0 vs 1), measurable disease (yes vs no), and prior chemoradiation (yes vs no). Treatment will continue until disease progression, initiation of new anticancer treatment, unacceptable adverse events, or withdrawal of consent for up to 35 cycles for pembro or 7 cycles of paclitaxel and carboplatin CT. Primary endpoints are PFS per RECIST v1.1, assessed by blinded independent central review, and OS. Secondary endpoints are ORR, health-related quality of life, safety and tolerability, and pharmacokinetics of lenvatinib. Exploratory endpoints include duration of response, disease control rate, and clinical benefit rate. Enrollment is ongoing. Clinical trial identificationNCT03884101; 21, 2019. Editorial acknowledgementNathan Rodeberg, PhD, and Diane Neer, ELS, of MedThink SciCom, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc. Legal entity responsible for the studyMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA, are responsible for the governance, coordination and running of the study. FundingFunding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA. DisclosureC. Vulsteke: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Janssen; Honoraria (self): Novartis; Honoraria (self): Leo-Pharma; Honoraria (self): Merck MSD; Honoraria (self): AstraZeneca; Honoraria (self): Astellas. V. Makker: Advisory / Consultancy: Eisai; Advisory / Consultancy: Merck; Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: ArQule; Research grant / Funding (self): Karyopharm; Research grant / Funding (self): AstraZeneca. I.A. McNeish: Honoraria (self): Clovis Oncology; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Tesaro. L. Dutta: Full / Part-time employment: Eisai. C. Xu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. S.M. Keefe: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. J. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. S. Pignata: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Honoraria (self): Clovis Oncology; Honoraria (self): Tesaro; Honoraria (self): Inctre. All other authors have declared no conflicts of interest.

843O - Apalutamide (APA) and overall survival (OS) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Updated results from the phase III SPARTAN study

843O - Apalutamide (APA) and overall survival (OS) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Updated results from the phase III SPARTAN study

1005P - Evaluation of niraparib 200 mg/d as maintenance therapy in recurrent ovarian cancer and associated thrombocytopenia in a real-world US setting

BackgroundNiraparib, a poly(ADP-ribose) polymerase inhibitor approved in 2017 by the US FDA (300mg/d), has proven to be efficacious as maintenance therapy in patients (pts) with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (ROC) who are in complete or partial response (PR) to platinum-based chemotherapy (CT), with dose modification recommended to manage adverse reactions. This study assessed the rates of thrombocytopenia (TCP) among ROC pts who initiated niraparib 200mg/d in a real-world US setting. MethodsIn July 2018, we recruited experienced (practicing ≥5 years) oncologists (N=107), who were directly involved in treatment decisions, to complete an online survey and chart review (minimum of 1 and maximum of 2 charts) of adult pts (N=150) with ROC who initiated niraparib 200mg/d within 12 weeks of CT and had ≥3 months of follow-up. Data on pt demographics, disease history, comorbidities, biomarker status (BRCA and homologous recombination deficiency [HRD]), treatment use, and platelet counts (PC) were collected. Data were analyzed using descriptive statistics. ResultsAbout 56% and 44% of pts received 1 and ≥2 lines of CT, respectively, and 55% had a PR to platinum-based CT immediately before niraparib initiation. Pts had stage III (39%) and stage IV (40%) ROC at diagnosis, with a mean disease duration of 1.3 years. BRCA and HRD testing occurred in 87 (58%) and 44 pts (29%), respectively. When asked the reason for initiating niraparib at 200mg/d, 40% of oncologists reported starting all pts at 200mg/d, 37% reported pt preference, 33% reported pt concern of toxicity, and 28% reported pt weight (median: 71kg). Grade 3/4 TCP (per NCI CTCAE v4.03) occurred in 14% of pts post-initiation. Median time from niraparib initiation to the first PC test was 25.5 days. Of 77 pts (51%) with >1PC test, median time from the first to the next test was 28 days. ConclusionsIn this chart review study, <1 in 5 pts had TCP (grade 3/4) and the median time from initiation to PC test was 25.5 days, both of which are lower than observed rates reported in the ENGOT-OV16/NOVA trial. Niraparib dose initiation at 200mg/d may be beneficial in managing adverse reactions in pts with ROC. Legal entity responsible for the studyTesaro: A GSK Company. FundingTesaro: A GSK Company. DisclosureP. Thaker: Research funding: Merck, Tesaro; Grant for research / Consulting: Celsion Pharmaceuticals, AstraZeneca, Tesaro, Merck, AbbVie, Lovance, Unleash Oncolytics, Immunogen, Stryker. K. Travers: Full / Part-time employment: Tesaro: A GSK Company. C. Karki: Full / Part-time employment: Ipsos Insights, LLC. R.P. Patel: Full / Part-time employment: Ipsos Insights, LLC. C. Krebsbach: Full / Part-time employment: Ipsos Insights, LLC. B. Harrow: Full / Part-time employment: Tesaro: A GSK Company. S.N. Westin: Research Funding: ArQule; AstraZeneca; Bayer; Biomarin; Celgene (I); Clovis Oncology; Cotinga Pharmaceuticals; Critical Outcome Technologies; Karyopharm Therapeutics (I); Kite Pharma (I); Novartis; Roche/Genentech; Tesaro; Consulting / Advisory Role: AstraZeneca, BioAscent, Casdin Capital, Clovis Oncology, Genentech, Gerson Lehrman Group, Medivation, Medscape, Merck, Ovation Sciences, Pfizer, Roche, Tesaro, Vaniam Group, Vermillion, Watermark Research Partners.