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Displaying One Session

Proffered Paper session
Date
Sat, 10.09.2022
Time
10:15 - 11:45
Location
4.B - Brest Auditorium
Chairs
  • Thomas B. Powles (London, United Kingdom)
  • Rana R. McKay (La Jolla, United States of America)
Session Type
Proffered Paper session
Proffered Paper session

LBA66 - IMmotion010: Efficacy and safety from the phase III study of atezolizumab (atezo) vs placebo (pbo) as adjuvant therapy in patients with renal cell carcinoma (RCC) at increased risk of recurrence after resection

Presentation Number
LBA66
Speakers
  • Axel Bex (London, United Kingdom)
Lecture Time
10:15 - 10:25
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45

Abstract

Background

The standard of care for loco-regional RCC is nephrectomy, but many patients (pts) experience recurrence. IMmotion010, a Phase III, multicentre, randomised, pbo-controlled, double-blinded trial, evaluated atezo (anti-PD-L1) monotherapy as adjuvant therapy in pts with RCC and increased risk of recurrence after resection.

Methods

Key eligibility criteria included pts with RCC with a clear-cell or sarcomatoid component and who had increased risk of recurrence (T2 Grade [Gr] 4, T3a Gr 3/4, T3b/c or T4 any Gr, TxN+ any Gr or M1 resected with no evidence of disease). Pts were randomised 1:1 to atezo 1200 mg IV q3w or pbo IV q3w for 16 cycles or 1 year. The primary endpoint was investigator (INV)-assessed disease-free survival (DFS). Secondary endpoints included OS and independent review facility (IRF)-assessed DFS in the ITT population, and INV-DFS and IRF-DFS in pts with PD-L1 immune cell expression ≥1% (VENTANA SP142 IHC assay).

Results

From 3 Jan 2017 to 15 Feb 2019, 778 pts were randomised to atezo (n=390) or pbo (n=388). At primary analysis data cutoff (3 May 2022), median follow-up was 44.7 mo and minimum follow-up was 38.6 mo. No pts remain on study treatment. Baseline characteristics were generally balanced between arms. Median INV-DFS was 57.2 mo (95% CI: 44.6, NE) for atezo and 49.5 mo (47.4, NE) for pbo (HR: 0.93; 95% CI: 0.75, 1.15; P=0.495). Key secondary endpoints are in the Table. In the safety population, Gr 3/4 adverse events (AEs) occurred in 27% (106/390) and 21% (81/383) of pts receiving atezo or pbo, respectively; Gr 5 AEs occurred in <1% (1/390) and <1% (3/383), none related to treatment.

Conclusions

Atezo as adjuvant therapy after resection for pts with RCC with increased risk of recurrence did not improve clinical outcomes vs pbo in the ITT population but had a manageable safety profile. Subgroup data will be presented. Table

Key endpoints Atezo Pbo HR (95% CI)
ITT n=390 n=388
INV-DFS
   n (%) 164 (42) 168 (43)
   Median (95% CI), mo 57.2 (44.6, NE) 49.5 (47.4, NE) 0.93 (0.75, 1.15)
OS
   n (%) 54 (14) 53 (14)
   Median (95% CI), mo NE (59.8, NE) NE (NE, NE) 0.97 (0.67, 1.42)
IRF-DFS
   n (%) 125 (32) 138 (36)
   Median (95% CI), mo NE (54.1, NE) NE (49.4, NE) 0.87 (0.69, 1.12)
PD-L1 ≥1% n=232 n=235
INV-DFS
   n (%) 93 (40) 105 (45)
   Median (95% CI), mo 57.2 (44.6, NE) 47.9 (38.6, NE) 0.83 (0.63, 1.10)
IRF-DFS
   n (%) 71 (31) 92 (39)
   Median (95% CI), mo NE (NE, NE) NE (41.4, NE) 0.75 (0.55, 1.03)

DFS, disease-free survival; ITT, intention-to-treat; NE, not estimable; OS, overall survival.

Clinical trial identification

NCT03024996.

Editorial acknowledgement

Medical writing assistance was provided by Scott Battle, PhD, of Health Interactions and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

A. Bex: Financial Interests, Institutional, Research Grant, Restricted educational grant for an investigator initiated trial of neoadjuvant therapy in high risk renal cancer: Pfizer; Non-Financial Interests, Principal Investigator, Steering committee member and PI in an adjuvant trial: Roche/Genentech; Non-Financial Interests, Principal Investigator, Steering committee member and local investigator in an adjuvant trial: BMS; Non-Financial Interests, Advisory Role, Medical Steering committee member to advise the patient advocacy group on medical topics and strategy: International Kidney Cancer Coalition, KIdney Cancer Association. R. Uzzo: Financial Interests, Personal, Advisory Role: Pfizer, Merck. J.A. Karam: Financial Interests, Personal, Other, Honoraria: Pfizer, Merck, Roche/Genentech, J&J; Financial Interests, Personal, Advisory Role: Pfizer, Merck, Roche/Genentech, J&J; Financial Interests, Institutional, Sponsor/Funding: Roche/Genentech, Mirati, Merck, Elypta; Financial Interests, Personal, Stocks/Shares: MedTek, ROM Technologies. V.A. Master: Financial Interests, Personal, Advisory Role: Pfizer, Merck, BMS, Ethicon. F. Donskov: Financial Interests, Institutional, Research Grant: Pfizer, MSD, Ipsen. C. Suárez: Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Pfizer, Roche, Astellas, Ipsen, Sanofi, Bayer, MSD; Financial Interests, Institutional, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, Astellas, Ipsen; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Other, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Pfizer, Roche. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Other, Scientific Committee: BMS France. B.I. Rini: Financial Interests, Personal, Advisory Board: Merck, BMS, AVEO, Alkermes, Pfizer, Eisai, Corvus, EUSA, Allogene, Debiopharm, Athenex, Surface Oncology, Genentech/Roche; Financial Interests, Personal, Stocks/Shares: PTC Therapeutics; Financial Interests, Institutional, Invited Speaker: Merck, Pfizer, Astra-Zeneca, Pionyr, Surface Oncology; Financial Interests, Institutional, Other, Research funding to institution: BMS, Arrowhead, Aravive; Financial Interests, Institutional, Funding: AVeo. Y. Tomita: Financial Interests, Personal, Invited Speaker: Astellas, BMS, Merk, Ono; Financial Interests, Institutional, Research Grant: Chugai, Ono; Non-Financial Interests, Advisory Role: Eisai, Ono. G. Procopio: Financial Interests, Personal, Advisory Board, consultant fees: Astellas, AstraZeneca, Bayer, BMS, Janssen, Ipsen, Merck, MSD, Novartis, Pfizer; Financial Interests, Institutional, Research Grant, research funding for no profit clinical trial: Opsen. M. Zibelman: Financial Interests, Personal, Advisory Role: Pfizer, EMD Serono, Exelixis, Janssen, Blue Earth; Financial Interests, Institutional, Research Grant: BMS, Exelixis. M. Huseni: Financial Interests, Personal, Full or part-time Employment: Genentech. D. Basu: Financial Interests, Personal, Full or part-time Employment: Roche. B. Ci: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. W. Leung: Financial Interests, Personal, Full or part-time Employment: Genentech. O. Khan: Financial Interests, Personal, Full or part-time Employment: Roche. S.K. Pal: Financial Interests, Personal, Advisory Role: Astellas Pharma, Aveo, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Ipsen, Myriad Pharmaceuticals, Novartis, Pfizer. All other authors have declared no conflicts of interest.

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Proffered Paper session

LBA67 - Phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a National Clinical Trials Network trial

Presentation Number
LBA67
Speakers
  • Mohamad Allaf (Boston, United States of America)
Lecture Time
10:25 - 10:35
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45

Abstract

Background

We conducted a phase III randomized open label trial priming the immune system with neoadjuvant nivo prior to nephrectomy followed by adjuvant nivo in pts with high risk RCC compared to surgery alone.

Methods

Entry criteria included patients with clinical stage ≥T2 or TanyN+ RCC planned for nephrectomy (partial or radical). Select oligometastatic disease was permitted if the pt could be rendered ‘no evidence of disease’ within 12 weeks of surgery. In the investigational arm, nivo was administered (480mg IV q4 weeks) with 1 dose prior to surgery followed by 9 adjuvant doses. The control arm was surgery followed by surveillance without a placebo. Baseline tumor biopsy was required only in the nivo arm. Primary endpoint was recurrence free survival (RFS) regardless of histology. Secondary endpoints include clear cell RCC RFS, overall survival (OS), and quality of life measures.

Results

Between 2/2017 and 6/2021, 819 pts were randomized to perioperative nivo (n=404) or surgery alone (n=415). Clinical stage at enrollment was 53% cT2, 47% cT3-4, 17% cN1, and 4% cM1; 83% of pts had clear cell RCC. The trial was stopped early by DSMC due to futility. RFS was similar between the arms (HR: 0.97; 95% CI: [0.74 – 1.28]; P1-sided = 0.43). The median RFS was not reached. OS was not mature at the time of analysis but was not statistically different between study arms (HR: 1.48; 95% CI: [0.89 – 2.48]; P1-sided = 0.93). Similar withdrawal rates occurred in both arms, approximately 12% (48/404 patients in nivo arm vs. 50/415 in surgery alone arm). 20% of patients treated with nivo experienced at least one Grade 3-4 AE that could be attributable to nivo, compared with 6% in the control arm. The most common treatment related grade 3-4 AEs were kidney injury (1% vs. 2%), rash (2% vs. 0%), and elevated lipase (4% vs. <1%). There were 15 (4%) deaths from RCC in the nivo arm and 18 (4%) deaths from RCC in the surgery alone arm.

Conclusions

Perioperative nivo did not improve RFS in RCC patients at high risk for recurrence. OS data remains immature but is not statistically different between arms. Subset analyses including risk stratification by pathologic stage are ongoing.

Clinical trial identification

NCT03055013; Study start date: February 2, 2017.

Legal entity responsible for the study

This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs).

Funding

National Cancer Institute of the National Institute of Health and the Canadian Cancer Society.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper session

Invited Discussant LBA66 and LBA67

Speakers
  • Thomas B. Powles (London, United Kingdom)
Lecture Time
10:35 - 10:45
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45
Proffered Paper session

Q&A

Speakers
  • All Speakers (Lugano, Switzerland)
Lecture Time
10:45 - 11:00
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45
Proffered Paper session

1735O - PD-L1 expression on immune cells by SP142 co-localises with dendritic cells and is associated with improved overall survival (OS) with atezolizumab in patients with untreated metastatic urothelial cancer (mUC)

Presentation Number
1735O
Speakers
  • Enrique Grande Pulido (Madrid, Spain)
Lecture Time
11:00 - 11:10
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45

Abstract

Background

PD-L1 assays use various methods (e.g., scoring tumour and/or immune cells) to predict PD-L1/PD-1 blockade outcomes. Data suggest that the clinically relevant PD-L1–expressing immune cells (IC) are dendritic cells (DCs) (Oh 2020). Here, we probed the clinical and immunologic basis underlying the trend toward favourable OS with atezolizumab alone (atezo; anti–PD-L1; Arm B) vs placebo + platinum/gemcitabine chemotherapy (chemo; Arm C) in patients (pts) with high PD-L1 by SP142 in the Ph 3 IMvigor130 trial (ITT: HR, 0.68, 95% CI: 0.43, 1.08; cisplatin ineligible: HR, 0.53, 95% CI: 0.30, 0.94) (Galsky ASCO-GU 2021; 31 May 2019 cutoff).

Methods

This post hoc analysis studied associations between 2 PD-L1 immunohistochemistry tests (VENTANA SP142 and Dako 22C3) and OS in pts with archival tumours (biomarker-evaluable [BioEval] pts) in IMvigor130 Arms B and C (14 Jun 2020 cutoff). Assay cutoffs were SP142 IC ≥5% (IC2/3)/<5% (IC0/1) and 22C3 combined positive score (CPS) ≥10/<10. Samples were also stained for IC subtypes.

Results

Demographics and OS of BioEval (n=627) and ITT (n=719) pts were similar. In deconvoluting the cellular components associated with PD-L1 staining, we found that SP142 preferentially co-localised with DCs (DC-LAMP, a DC-specific marker) as opposed to other myeloid subsets. Arm B OS by SP142 and/or 22C3 is shown in the table. Longer OS was associated with SP142 IC2/3 + 22C3 CPS ≥10 tumour status. Median OS was shortest in pts with tumours staining for 22C3 but not SP142 (SP142 IC0/1 + 22C3 CPS ≥10; Table).

Conclusions

This IMvigor130 exploratory analysis showed different OS trends with different PD-L1 assays. PD-L1–expressing DCs may underlie the longer OS with atezo in SP142 IC2/3 vs IC0/1 tumours in pts with mUC. These findings reinforce model system data demonstrating the particular importance of PD-L1–expressing DCs.

BioEval Arm B n=322
n Exploratory OS, mo HR (95% CI)
mOS 95% CI
IC2/3 79 27.5 15.7, NE 0.55 (0.39, 0.77)
IC0/1 243 13.1 11.0, 16.0
CPS ≥10 114 15.6 11.4, 21.8 0.83 (0.63, 1.09)
CPS <10 208 14.2 12.1, 17.5
IC2/3 + CPS ≥10 59 29.4 18.2, NE -
IC2/3 + CPS <10 20 12.9 8.7, NE
IC0/1 + CPS ≥10 55 8.9 5.8, 14.0
IC0/1 + CPS <10 188 14.3 12.1, 17.8
Cisplatin ineligible
IC2/3 46 18.6 13.1, NE -
IC0/1 120 10.2 6.2, 14.3
CPS ≥10 62 14.6 7.7, 18.9
CPS <10 114 12.5 8.7, 15.3
mOS, median OS; NE, not estimable.

Clinical trial identification

NCT02807636.

Editorial acknowledgement

Medical writing assistance was provided by Bena Lim, PhD, of MediTech Media and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

E. Grande Pulido: Financial Interests, Personal, Invited Speaker: Adacap, AstraZeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, IPSEN, Janssen, Lilly, Merck KGa, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Astellas, Bayer, MSD, Novartis, Sanofi-Genzyme; Financial Interests, Institutional, Advisory Board: Caris Life Sciences, ONCODNA (Biosequence); Financial Interests, Institutional, Research Grant, Independent research grant: Astellas, AstraZeneca, Lexicon, MTEM/Threshold, Nanostring Technologies, Pfizer, Roche, Merck; Financial Interests, Institutional, Invited Speaker, Independent research grant: Ipsen; Non-Financial Interests, Other, AD BOARD member: ENETS. M.D. Galsky: Financial Interests, Personal, Advisory Board: Janssen, Merck, GlaxoSmithKline, Eli Lilly, Astellas, Genentech, Bristol Myers-Squibb, Pfizer, EMD Serono, AstraZeneca, Seagen, Incyte, Alligator; Financial Interests, Personal, Other, Consultant: Rappta Therapeutics; Financial Interests, Institutional, Invited Speaker: Merck, AstraZeneca, Genentech, Jazz, Bristol Myers Squibb, Seagen. R. Van Elzen: Financial Interests, Personal, Full or part-time Employment: CellCarta. R. Banchereau: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. M. Peterson, C. Sedano, I. Mellman, S. Oh: Financial Interests, Personal, Full or part-time Employment: Genentech. H. Koeppen: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. H. Li, S. Bernhard, C.P. Lee: Financial Interests, Personal, Full or part-time Employment: Roche. A. Bamias: Financial Interests, Personal, Invited Speaker: Ipsen, Debiopharm; Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca; Financial Interests, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Roche, BMS, MSD; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer; Non-Financial Interests, Leadership Role: Hellenic GU Cancer Group. J.A. Arranz Arija: Financial Interests, Personal, Advisory Board: Astellas, BMS, Merck, Pfizer, Bayer, MSD, EISAI; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker, SOGUG: BMS. E. Kikuchi: Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Janssen, Kissei, Kyorin, Merck Biopharma, MSD, Nippon Kayaku, Nippon Shinyaku, Pfizer, Sanofi, Taiho, Takeda, Kyowa Kirin; Financial Interests, Personal, Advisory Role: Merck Biopharma, Astellas, Chugai, Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Kissei, Takeda, Taiho, Nippon Kayaku, Nippon Shinyaku. M. De Santis: Financial Interests, Personal, Advisory Board, Advisory functions, invited speaker,: Bioclin; Financial Interests, Personal, Advisory Board: AAA, Amgen, 4D, EISAI, Basilea, Merck/Serono, Bayer, BMS, Sanofi, Ipsen, Novartis/Sandoz, Immunomedics/Gilead, Roche, Ferring, SeaGen; Financial Interests, Personal, Advisory Board, invited speaker, advisory function: Astellas; Financial Interests, Personal, Advisory Board, invited speaker, steering committee member: AstraZeneca; Financial Interests, Personal, Advisory Board, invited speaker, advisory function, local PI: MSD; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board, Speaker fees: Pierre Fabre Oncology; Financial Interests, Personal, Invited Speaker, Steering committee, advisory Board: AAA; Financial Interests, Personal, Invited Speaker, advisory function: Amgen; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria: Astellas, AstraZeneca, 4D, Bayer, Novartis, Ipsen, Janssen; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria trial fees: EISAI; Financial Interests, Personal and Institutional, Invited Speaker, local PI, honoraria for advisory function, trial fees: Basilea; Financial Interests, Institutional, Invited Speaker: Calithera; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, local PI, honoraria, trial fees: MSD; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria,: Merck/Serono; Financial Interests, Personal and Institutional, Invited Speaker, Advisory function, honoraria, travel funding: BMS; Financial Interests, Institutional, Invited Speaker, trial fees: Nektar; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker, Advisory function, honoraria: Roche/Genentech; Financial Interests, Personal, Invited Speaker, advisory function, honoraria: Sandoz; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, local PI: Immunomedics/Gilead; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria, local PI: SeaGen; Financial Interests, Personal, Other, advisory function, honoraria: Ferring; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria, local and coordinating PI: Pierre Fabre; Non-Financial Interests, Member, writing and discussing guidelines for treatment and diagnostics: EAU Guidelines group prostate cancer; Non-Financial Interests, Member, Guidelines for bladder cancer treatment: S3 Leitlinie Blasenkrebs; Non-Financial Interests, Member: ESMO Clinical practice guidelines panel bladder cancer. I.D. Davis: Financial Interests, Personal, Royalties, Authorship royalties for: Health Press; Financial Interests, Personal, Other, Remuneration for associate editor role in Therapeutic Advances in Medical Oncology: SAGE; Financial Interests, Institutional, Invited Speaker, Institutional support for clinical research: Movember Foundation, Merck/MSD, Bristol Myers Squibb, Exelixis, Astellas, Pfizer, AstraZeneca, Roche / Genentech, Eisai, Bayer, Janssen, Ipsen, Seagen; Non-Financial Interests, Invited Speaker, Director and Chair: ANZUP Cancer Trials Group; Non-Financial Interests, Advisory Role, All honoraria and payments are made directly to ANZUP Cancer Trials Group with no pass-through payment: Roche, Janssen, Astellas, Bayer, Ipsen, MSD, Merck/Pfizer, AstraZeneca, Eisai, Bristol Myers Squibb, Pio Therapeutics; Non-Financial Interests, Other, Member of Council: Clinical Oncology Society of Australia. P. Williams: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech/Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genentech. M. Kockx: Financial Interests, Personal, Member of the Board of Directors: CellCarta; Financial Interests, Personal, Stocks/Shares: CellCarta. S. Mariathasan: Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Genentech.

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Proffered Paper session

LBA74 - Genomic biomarkers in peripheral blood (PB) from patients (pts) enrolled in the JAVELIN Bladder 100 trial of avelumab first-line (1L) maintenance in advanced urothelial carcinoma (aUC)

Presentation Number
LBA74
Speakers
  • Thomas B. Powles (London, United Kingdom)
Lecture Time
11:10 - 11:20
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45

Abstract

Background

The relationship between blood biomarkers, tumor immunity, and benefit from immune checkpoint inhibitors (ICIs) is not well understood. The JAVELIN Bladder 100 trial (NCT02603432) demonstrated that avelumab 1L maintenance prolongs overall survival (OS) in pts with aUC that has not progressed with 1L chemotherapy. Blood biomarkers associated with tumor immune gene signatures in this trial may provide mechanistic insight into the development of antitumor immunity and indicate patient subpopulations that could benefit from ICIs. We used EpiSwitch analysis of PB to identify structural-functional epigenetic changes in genomic architecture, designated chromatin conformation signatures (CCSs).

Methods

PB from 496 pts in the JAVELIN Bladder 100 trial underwent EpiSwitch analysis by PCR assay of 3D genomic templates prepared from fixed intact nuclei. Tumor immune activity was scored using a gene expression signature (JAVELIN Renal 101 Immune [JR101I]). CCS association with tumor JR101I scores was determined via univariate and multivariate analyses of a training set of 80 specimens.

Results

We identified 25 CCSs from the training set. One CCS was proximal to POU2F2, a transcription factor instrumental in B cell development. Patients whose PB lacked the POU2F2 CCS had elevated tumor JR101I scores, corresponding to increased gene expression associated with tertiary lymphoid structures (TLSs). The POU2F2 CCS may therefore influence key steps in TLS formation. In patients with a median tumor mutation burden (TMB) of ≤ 7.66 non-synonymous SNVs per Mb, the avelumab+BSC vs BSC hazard ratios in the CCS-absent subpopulation was 0.56 (95% CI, 0.32–0.96; p=0.037; n=83); and in the CCS-present population was 1.2 (95% CI, 0.83–1.75; P=0.34; n=158). CCSs affecting the ability to form TLSs may influence response to avelumab at low TMB.

Conclusions

PB CCSs may be associated with TLS, tumor JR101I scores, and the degree of OS benefit. These findings support further analysis of CCSs to assess potential clinical utility.

Editorial acknowledgement

Medical writing support was provided by Abhijith Thippeswamy of ClinicalThinking, and was funded by Pfizer as part of an alliance between Pfizer and Merck.

Legal entity responsible for the study

Pfizer, as part of an alliance between Pfizer and Merck.

Funding

Pfizer, as part of an alliance between Pfizer and Merck (CrossRef Funder ID: 10.13039/100009945).

Disclosure

T.B. Powles: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb, Merck, AstraZeneca, Ipsen, Pfizer, Novartis, Incyte, Seattle Genetics, Roche, Exelixis, MSD, Astellas Pharma, Johnson & Johnson, Eisai; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, MSD, AstraZeneca, Roche, Ipsen; Financial Interests, Personal, Research Grant: AstraZeneca, Roche, Bristol-Myers Squibb, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Astellas Pharma, Johnson & Johnson, Eisai. S. Sridhar: Financial Interests, Personal, Advisory Role, Consulting: Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Hoffmann-La Roche, Immunomedics, Ipsen, Janssen, Merck, Pfizer, Seagen, Roche, Seattle Genetics; Financial Interests, Personal, Research Grant: Bayer, Janssen, Seagen. J. Bellmunt: Financial Interests, Personal, Other, Honoraria (Self): Pfizer, MSD, BMS, AstraZeneca, Pierre Fabre; Financial Interests, Institutional, Other, Honoraria (Institution): Takeda, MSD; Financial Interests, Personal, Advisory Board: Pfizer, MSD, BMS, AstraZeneca, Roche /Genentech, Pierre Fabre; Financial Interests, Institutional, Research Grant: Takeda, Pfizer; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Pfizer; Financial Interests, Personal, Licensing Fees: UpToDate. C. Sternberg: Financial Interests, Personal, Advisory Role: Pfizer, MSD, Merck, AstraZeneca, Astellas, Sanofi-Genzyme, Roche-Genentech, Incyte, Medscape, Janssen, UroToday, Foundation, Medicine, Immunomedics, NCI, Impact Pharmaceuticals, Bristol Myers Squibb. P. Grivas: Financial Interests, Personal, Advisory Role: AstraZeneca, Astellas Pharma, Bayer, Bristol Myers Squibb, Dyania Health, Merck, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Guardant Health, Gilead Sciences, Infinity Pharmaceuticals, Janssen, Lucence Health, Mirati Therapeutics, Pfizer, QED Therapeutics, Regeneron Pharmaceuticals, SilverBack Therapeutics, UroGen, 4D Pharma PLC, EMD Serono; Financial Interests, Institutional, Advisory Role: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Bavarian Nordic; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Clovis Oncology, Debiopharm, Merck, G1 Therapeutics, Gilead Sciences, GlaxoSmithKline, Mirati Therapeutics, Pfizer, QED Therapeutics, EMD Serono. E. Hunter: Financial Interests, Personal, Full or part-time Employment: Oxford Biodynamics Plc; Financial Interests, Personal, Stocks/Shares: Oxford Biodynamics Plc. M. Dezfouli: Financial Interests, Personal, Full or part-time Employment: Oxford BioDynamics Plc. M. Salter: Financial Interests, Personal, Full or part-time Employment: Oxford Biodynamics Plc; Financial Interests, Personal, Stocks/Shares: Oxford BioDynamics Plc. R. Powell: Financial Interests, Personal, Full or part-time Employment: Oxford Biodynamics Plc; Financial Interests, Personal, Stocks/Shares: Oxford Biodynamics Plc. A. Dring: Financial Interests, Personal, Full or part-time Employment: Oxford BioDynamics Plc; Financial Interests, Personal, Stocks/Shares: Oxford BioDynamics Plc. J. Green: Financial Interests, Personal, Full or part-time Employment: Oxford Biodynamics Plc; Financial Interests, Personal, Stocks/Shares: Oxford Biodynamics Plc. A. Akoulitchev: Financial Interests, Personal, Full or part-time Employment: Oxford Biodynamics Plc; Financial Interests, Institutional, Research Grant: PACT-FNIH; Financial Interests, Personal, Stocks/Shares: Oxford Biodynamics Plc, Sibelius Natural Products Ltd. R. Amezquita: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. K. Ching: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. J. Pu: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. S. Deng: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. A. di Pietro: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. C.B. Davis: Financial Interests, Personal, Full or part-time Employment: Pfizer.

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Proffered Paper session

Invited Discussant 1735O and LBA74

Speakers
  • Rana R. McKay (La Jolla, United States of America)
Lecture Time
11:20 - 11:30
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45
Proffered Paper session

Q&A

Lecture Time
11:30 - 11:45
Location
4.B - Brest Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 10.09.2022
Time
10:15 - 11:45