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Displaying One Session

Channel 2 Proffered Paper session
Date
20.09.2020
Time
14:25 - 16:05
Room
Channel 2
Chairs
  • Silvia Formenti (New York, United States of America)
  • Ignacio Melero (Pamplona, Spain)
Proffered Paper - Investigational immunotherapy Proffered Paper session

LBA41 - LEAP-005: Phase II study of lenvatinib (len) plus pembrolizumab (pembro) in patients (pts) with previously treated advanced solid tumours

Presentation Number
LBA41
Lecture Time
14:25 - 14:37
Speakers
  • Zarnie Lwin (Herston, QLD, Australia)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05

Abstract

Background

Len (antiangiogenic multiple receptor tyrosine kinase inhibitor) + pembro (anti‒PD-1 agent) showed promising clinical outcomes across several cancers in early-phase trials and is FDA-approved for pts with previously treated advanced endometrial cancer that is not MSI-H or mismatch repair-deficient who are ineligible for curative surgery/radiation. We report the first results from the phase 2 LEAP-005 study (NCT03797326), which evaluates the efficacy and safety of len + pembro in pts with select previously treated advanced solid tumors.

Methods

This open-label, multicohort study enrolled pts aged ≥18 y with one of the following previously treated, histologically/cytologically confirmed advanced tumors: triple negative breast (TNBC), ovarian, gastric, colorectal (non-MSI-H/mismatch repair proficient), glioblastoma multiforme (GBM), or biliary tract (BTC; ampulla of Vater excluded). Pts received len 20 mg/d + pembro 200 mg Q3W for 35 cycles or until confirmed PD or unacceptable toxicity. Primary endpoints are ORR by blinded independent central review per RECIST v1.1 or RANO (GBM only), and safety.

Results

187 pts have been enrolled in LEAP-005. Median study follow-up at Apr 10, 2020 data cutoff was 8.6 (range, 1.9‒13.1) mo. Encouraging efficacy was observed across cohorts, and toxicity was manageable (Table).

Cohort
2L/3L TNBC (n = 31) 4L Ovarian (n = 31) 3L Gastric (n = 31) 3L Colorectal (n = 32) 2L GBM (n = 31) 2L BTC (n = 31)
ORR, % (95% CI) 29 (14–48) 32 (17–51) 10 (2–26) 22 (9–40) 16 (6–34) 10 (2–26)
DCR, n (%) 18 (58) 23 (74) 15 (48) 15 (47) 18 (58) 21 (68)
DOR, median (range), mo NR (0.0+ to 8.4+) NR (1.5+ to 7.9+) NR (2.1+ to 2.3+) NR (2.1+ to 10.4+) 3.2 (2.5 to 4.9+) 5.3 (2.1+ to 6.2)
Grade ≥3 treatment-related AEs, n (%) 17 (55) 21 (68) 13 (42) 16 (50) 11 (35) 15 (48)
Discontinued drug due to treatment-related AE, n (%) 3 (10) 4 (13) 2 (6) 3 (9) 2 (6) 2 (6)

+, no PD as of last disease assessment; DCR, disease control rate (best confirmed response: complete/partial response; stable disease); DOR, duration of response; NR, not reached.

Conclusions

Len + pembro showed promising antitumor activity and manageable toxicity across the previously treated tumor cohorts evaluated in LEAP-005. The study is ongoing; all cohorts will expand to enroll ≤100 pts/cohort.

Clinical trial identification

NCT03797326.

Editorial acknowledgement

Medical writing and editorial assistance was provided by Rozena Varghese, PharmD, CMPP, and Michael S. McNamara, MS, of ICON plc (North Wales, PA, USA). This assistance was cofunded by the study sponsors, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA.

Legal entity responsible for the study

Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

Z. Lwin: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; AstraZeneca; BMS; Roche; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. C. Gomez-Roca: Honoraria (self): Genentech/Roche, Pierre Fabre, AstraZeneca, and BMS; Advisory/Consultancy: Erytech, BMS, Roche/Genentech, Novartis, and Eisai; Research grant/Funding (institution): BMS and Roche/Genentech; Travel/Accommodation/Expenses: Pierre Fabre, BMS, Roche/Genentech, and MSD. E. Saada-Bouzid: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS and MSD; Travel/Accommodation/Expenses: AstraZeneca. E. Yanez: Research grant: Amgen, Pfizer, Astellas, BMS, Roche, AbbVie, MSD F. Longo Muñoz: Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD, BMS, Roche, Merck, Amgen, Lilly, Sanofi, Servier, Bayer, and Ferrer Pharma. S-A. Im: Research grant/Funding (self): AstraZeneca, Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Novartis, Roche, Hanmi Corp, and Pfizer. E. Castanon: Travel/Accommodation/Expenses: AstraZeneca, MSD, BMS, and Roche; Advisory/Consultancy: BMS, Roche, and BeiGene. D. Graham: Research grant/Funding (institution): Pfizer; Honoraria (self): Clinigen Group and McCann Health. M. Doherty: Research grant/Funding (self): Merck and AstraZeneca; Advisory/Consultancy, Consulting fees: AstraZeneca, Merck, Eisai, Boehringer Ingelheim, Takeda, Pfizer, and Roche. J. Lopez: Advisory/Consultancy: Eisai, Novartis, and Genmab; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche, Basilea Pharmaceutica, Genmab. R. Ghori, F. Jin, K. Norwood: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P. Kubiak: Full/Part-time employment: Eisai Inc., Woodcliff Lake, NJ, USA. H.C. Chung: Research grant/Funding (self): Lilly, GSK, MSD, Merck-Serono, BMS/Ono, Taiho, Amgen, BeiGene, Incyte; Honoraria (self): Lilly/Foundation Medicine; Consultation: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono, Gloria, BeiGene, Amgen, Zymeworks. All other authors have declared no conflicts of interest.

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Proffered Paper - Investigational immunotherapy Proffered Paper session

1019O - Phase I studies of Sym021, an anti-PD-1 antibody, alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)

Presentation Number
1019O
Lecture Time
14:37 - 14:49
Speakers
  • Nehal Lakhani (Grand Rapids, United States of America)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05

Abstract

Background

Although anti-PD-(L)1 Abs are efficacious in the treatment of various cancers, only a minority of patients benefit and many eventually relapse. Therefore, combination strategies are being pursued to further improve outcome. Sym021 is a humanized, effector-function silenced anti-PD-1 IgG1 mAb. Preclinical models demonstrate that Sym021 combined with Abs targeting other checkpoints (e.g., Sym022, anti-LAG-3; Sym023, anti-TIM-3) results in enhanced immunostimulatory and antitumor activity. We present here first-in-human studies of Sym021, Sym022, and Sym023 alone and Sym021 in combination with either Sym022 or Sym023.

Methods

Safety, tolerability, and activity of single agent Sym021, Sym022, or Sym023 and combinations were evaluated at escalating doses up to 10-20 mg/kg on a Q2W schedule in patients (pts) with advanced solid tumors or lymphomas. Samples were collected for assessment of PK profiles, immunogenicity, and pharmacodynamic markers in all pts.

Results

Dose escalation studies of Sym021, 022, and 023 as single agents have been completed. The MTD was not reached for any single agent. The Sym021 dose was fixed at 3 mg/kg based on PK/PD analysis for subsequent dose escalation in combination with Sym022 or Sym023. The MTD was not reached for either combination. Number of pts treated, the most commonly observed Grade 3-4 treatment-related adverse events (TRAEs) as well as objective responses are detailed in the table below. Assessment of PK, immunogenicity, and pharmacodynamic markers is ongoing.

Grade 3-4 TRAE/Responses N (%) Sym021 N=17 Sym022 N=15 Sym023 N=24 Sym021+022 N=20 Sym021+023 N=17
Lipase increase 1 (5.9) 0 0 0 0
CPK increase 0 0 0 2 (10) 0
ALT increase 0 0 0 0 1 (5.9)
Lymphocytes decrease/Lymphopenia 0 0 0 1 (5) 1 (5.9)
Immune mediated (IM) arthritis 1 (5.9) 0 1 (4.2) 0 0
IM hypophysitis 0 0 0 1 (5) 0
IM enterocolitis 1 (5.9) 0 0 0 0
Fatigue 0 0 1 (4.2) 0 1 (5.9)
Cough 0 0 0 0 1 (5.9)
Rash 0 0 0 0 1 (5.9)
RESPONSES 1 CR, 1 PR 1 PR* 0 1 PR* 2 PRs

CR, Complete response; PR, Partial response; *Unconfirmed.

Conclusions

Sym021, Sym022 and Sym023 alone and Sym021 in combination with either Sym022 or Sym023 were well tolerated with AE profiles typical of immune checkpoint inhibitors. Responses were observed with single agent Sym021 and Sym022, and with both combinations. Evaluation of the antitumor activity of Sym021+022 and Sym021+023 doublets in select tumor types post-PD-(L)1 treatment is planned.

Clinical trial identification

NCT03311412; NCT03489369; NCT03489343.

Legal entity responsible for the study

Symphogen.

Funding

Symphogen.

Disclosure

N. Lakhani: Honoraria (self): Innovent Biologics; Research grant/Funding (institution): ALX Therapeutics, Ascentage, Livzon, Asana Biosciences, Beigene, Innovent Biologics, Constellation Pharma, Alexion, Ikena, Cerulean, Odonate, Forty Seven, Loxo, Macrogenics, Merck, Pfizer, Regeneron, TaiRx, Apexian, Formation Biologics, Symphogen, CytomX. A. Spreafico: Research grant/Funding (institution): Novartis, Bristol-Myers Squibb, Symphogen, AstraZeneca/MedImmune, Merck, Bayer, Surface Oncology, Northern Biologics, Janssen Oncology/Johnson & Johnson, Roche, Regeneron, Alkermes, Array Biopharma; Advisory/Consultancy: Merck, Bristol-Myers Squibb, Novartis, Oncorus, Janssen. A.W. Tolcher: Advisory/Consultancy: Nanobiotix, Pierre Fabre, Ascentage Pharma, AbbVie, EMD Serono, BioInvent, Adagene, ADC Therapeutics, Agenus, Aximmune, Bayer, Boston Biomedical, Forbius (formerly Formation Biologics), HBM Partners, Mekanistic, NBE Therapeutics, Nuvalent, Pelican, Pfizer; Research grant/Funding (institution): AbbVie, Pfizer, Syndax, Asana Biosciences, ADC Therapeutics, Adagene, Aminex, Ascentage Pharma, Arrys, CStone Pharmaceuticals, Deciphera, GlaxoSmithKline, Inhibrx, Innate Pharma, Kiromic, Mersana, Naturewise, NextCure, Nitto BioPharma, Pieris Pharmaceutic. J. Rodon: Travel/Accommodation/Expenses: European Journal of Cancer, Vall d'Hebron Institut of Oncology, Chinese University of Hong Kong, SOLTI, Elsevier, GlaxoSmithKline; Advisory/Consultancy: Novartis, Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Peptomyc, Merck Sharp & Dohme, Kelun Pharmaceutical/Klus Pharma, Spectrum Pharmaceuticals Inc, Pfizer, Roche Pharmaceuticals, Ellipses Pharma, NovellusDx, Ionctura and Molecular Partners; Research grant/Funding (self): Blueprint Pharmaceuticals, Bayer and Novartis; Honoraria (institution): Spectrum Pharmaceuticals, Tocagen, Symphogen, BioAtla, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GlaxoSmithKline, Ipsen; Travel/Accommodation/Expenses: from ESMO, US Department of Defense, Louissiana State University, Hunstman Cancer Institute, Cancer Core Europe, Karolinska Cancer Institute and King Abdullah International Medical Research Center (KAIMRC), Molecular Partners. F. Janku: Research grant/Funding (self): Novartis, Genentech, BioMed Valley Discoveries, Astellas, Agios, Plexxikon, Deciphera, Piqur, Symphogen, Bristol-Myers Squibb, Asana, Upsher-Smith Laboratories; Advisory/Consultancy: Guardant Health, IFM Therapeutics, Synlogic, and Deciphera; is a paid consultant for Trovagene, Immunomet, Symphogen; Shareholder/Stockholder/Stock options: Trovagene. S.R. Chandana: Honoraria (institution): Alexo, Amgen, Apexian, Asana, Ascentage, Astellas, AstraZeneca, Beigene, Bolt Biotherapeutics, Bristol-Myers Squibb, Compugen, Coordination, Constellation, CytomX, Effector Therapeutics, Exelixis, Formation Biologics, Forty Seven, Ikena, Innovent Biologi; Advisory/Consultancy: Ipsen, JNJ, Amgen, BMS, Astellas, Dicephera, Array Biopharma. M. Oliva: Advisory/Consultancy: BMS; Advisory/Consultancy, Research grant/Funding (self): Mirati Therapeutics; Research grant/Funding (self): Nubyota; Research grant/Funding (institution): Symphogen; Travel/Accommodation/Expenses: MSD Oncology; Travel/Accommodation/Expenses: Merck. M. Sharma: Honoraria (institution): Alexo, Amgen, Apexian, Asana, Ascentage, Astellas, AstraZeneca, Beigene, Bolt Biotherapeutics, Bristol-Myers Squibb, Compugen, Coordination, Constellation, CytomX, Effector Therapeutics, Exelixis, Formation Biologics, Forty Seven, Ikena, Innovent Biologi. R.M. Abdul-Karim: Research grant/Funding (institution): Oric Pharmaceuticals, Synthorx Inc., Adagene, Gilead Sciences, Boston Biomedical, Amphivena Therapeutics Inc., Inhibrx Inc., Pfizer, BJ Bioscience Inc., Spring Bank Pharmaceuticals Inc., Petra Pharma, eFEFECTOR Therapeutics Inc., Takeda, Basilea Pharmaceutica. U.H. Hansen, L. Hansen, N.J.Ø. Skartved, T.T. Poulsen: Full/Part-time employment: Symphogen R.P. Nadal: Advisory/Consultancy, Full/Part-time employment: Symphogen. J. Lantto: Full/Part-time employment: Symphogen A/S. D.L. Wood: Advisory/Consultancy: Symphogen; Advisory/Consultancy: Forbius; Advisory/Consultancy: Tessa Therapeutics; Spouse/Financial dependant: Karyopharm. P.I. Nadler: Advisory/Consultancy, Leadership role: Forbius; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Karyopharm; Advisory/Consultancy: Tessa Therapeutics. L.L. Siu: Research grant/Funding (institution): Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca/MedImmune, Merck, Celgene, Astellas, Bayer, AbbVie, Amgen, Symphogen, Intensity Therapeutics, Mirati, Shattucks, Avid; Advisory/Consultancy: Merck, Pfizer, Celgene, AstraZeneca/MedImmune, Morphosys, Roche, Loxo, Oncorus, Symphogen, Seattle Genetics, GSK, Voronoi, Treadwell Therapeutics, Tessa, Navire, Relay Therapeutics, Rubius Therapeutics; Honoraria (institution): Arvinas; Leadership role: Treadwell therapeutics; Officer/Board of Directors: AACR.

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Proffered Paper - Investigational immunotherapy Proffered Paper session

Invited Discussant LBA41 and 1019O

Lecture Time
14:49 - 14:59
Speakers
  • Ignacio Melero (Pamplona, Spain)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05
Proffered Paper - Investigational immunotherapy Proffered Paper session

Q&A and live discussion

Lecture Time
14:59 - 15:09
Speakers
  • Silvia Formenti (New York, United States of America)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05
Proffered Paper - Investigational immunotherapy Proffered Paper session

1020O - A phase I, first-in-human, open-label, dose escalation study of MGD019, an investigational bispecific PD-1 x CTLA-4 DART® molecule in patients with advanced solid tumours

Presentation Number
1020O
Lecture Time
15:09 - 15:21
Speakers
  • Manish Sharma (Grand Rapids, MI, United States of America)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05

Abstract

Background

MGD019 is a bispecific, Fc-bearing (IgG4) DART molecule that blocks PD-1 and CTLA-4, with increased activity on dual PD-1/CTLA-4-expressing cells. MGD019 enhances in vitro T-cell responses to levels achieved by a combination of nivolumab and ipilimumab replicas. MGD019 was well tolerated in cynomolgus monkeys, with biological evidence of CTLA-4 antagonism but a safety profile similar to PD-1 blockade alone. MGD019 may offer risk/benefit improvements vs PD-1 plus CTLA-4 combinations.

Methods

This study characterizes safety, tolerability, dose-limiting toxicities, maximum tolerated dose (MTD), PK/PD, and preliminary antitumor activity of MGD019 in patients (pts) with advanced solid tumors. Dose Escalation enrolled pts in a 3+3+3 design up to 10 mg/kg. Cohort Expansion will further characterize safety and antitumor activity per RECIST v1.1 in pts treated at the MTD/MAD.

Results

At data-cutoff, 33 pts (39% checkpoint-experienced, 3 median prior lines of therapy) were treated in Dose Escalation from 0.03 to 10 mg/kg. No MTD was defined. Treatment-related adverse events (TRAEs) occurred in 26/33 (78.8%) pts, most commonly fatigue (24%), nausea, arthralgia, pruritus, and rash (18% each). The rate of Grade ≥ 3 TRAEs was 24.2%. Immune-related SAEs included enteritis, enterocolitis, pneumonitis, and myocarditis (n=1 each). Half-life was 12 days; full on-target binding to circulating T cells sustained through trough was observed at doses ≥ 3.0 mg every 3 weeks. Among 25 response-evaluable pts, 4 objective responses were observed (microsatellite stable colorectal cancer, metastatic thymoma [both confirmed PRs], anti-PD-L1-refractory serous fallopian tube carcinoma [unconfirmed PR with >50% reduction of CA-125], and prostatic adenocarcinoma [confirmed CR with resolution of PSA]); 9 pts had stable disease. Dose-dependent ICOS upregulation on circulating CD4+ T cells was evident, consistent with CTLA-4 engagement. Potential correlative biomarkers are being investigated.

Conclusions

MGD019 has demonstrated an acceptable safety profile and encouraging early evidence of anti-tumor activity.

Clinical trial identification

NCT03761017.

Legal entity responsible for the study

MacroGenics, Inc.

Funding

MacroGenics, Inc.

Disclosure

M. Sharma: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Bayer; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bolt Biotherapeutics; Research grant/Funding (institution): Compugen; Research grant/Funding (institution): Coordinaton; Research grant/Funding (institution): Effector Therapeutics; Research grant/Funding (institution): Ikena; Research grant/Funding (institution): InhibRx; Research grant/Funding (institution): Klus; Research grant/Funding (institution): MacroGenics; Research grant/Funding (institution): Symphogen; Research grant/Funding (institution): Syros; Research grant/Funding (institution): Tempest Therapeutics; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Alpine; Research grant/Funding (institution): Genmab; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Shattuck; Research grant/Funding (institution): Sapience. R.E. Sanborn: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Peregrine Pharmaceuticals; Advisory/Consultancy: ARIAD/Takeda; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Celldex; Advisory/Consultancy: AbbVie; Research grant/Funding (self): Merck; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): MedImmune. G.M. Cote: Advisory/Consultancy, Research grant/Funding (institution): Agios; Advisory/Consultancy, Research grant/Funding (institution): PharmaMar; Advisory/Consultancy, Research grant/Funding (institution): Epizyme; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): MacroGenics; Research grant/Funding (institution): Plexxicon; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): CBA; Research grant/Funding (institution): Springworks; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Bavarian Nordic; Advisory/Consultancy, Medical Advisory Board: Chordoma Foundation; Advisory/Consultancy, Scientific Advisory Committee: Angiosarcoma AwarenessFoundation. J.C. Bendell: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Stemcentrx; Research grant/Funding (institution): ADC Therapeutics; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Arcus Biosciences; Research grant/Funding (institution): ARMO Biosciences; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): Arrys Therapeutics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): Bellicum Pharmaceuticals; Research grant/Funding (institution): Bicycle Therapeutics; Research grant/Funding (institution): Blueprint Medicine; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): BMS; Research grant/Funding (institution): CALGB; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Cyteir Therapeutics; Research grant/Funding (institution): CytomX; Research grant/Funding (institution): eFFECTOR Therapeutics; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Evelo Biosciences; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Five Prime Therapeutics; Research grant/Funding (institution): Forty Seven. S. Kaul: Shareholder/Stockholder/Stock options: AbbVie; Shareholder/Stockholder/Stock options: Bristol-Myers Squibb; Shareholder/Stockholder/Stock options: Johnson & Johnson; Shareholder/Stockholder/Stock options: Merck; Shareholder/Stockholder/Stock options: CVS; Shareholder/Stockholder/Stock options: Walgreens; Shareholder/Stockholder/Stock options: Abbott; Shareholder/Stockholder/Stock options: Baxter; Shareholder/Stockholder/Stock options: Boston Scientific; Shareholder/Stockholder/Stock options: Medtronics; Shareholder/Stockholder/Stock options: United Healthcare; Advisory/Consultancy: MacroGenics; Advisory/Consultancy, Travel/Accommodation/Expenses: PharmaEssentia; Advisory/Consultancy: Bristol-Myers Squibb. F. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: MacroGenics, Inc. A. Berezhnoy: Shareholder/Stockholder/Stock options, Full/Part-time employment: MacroGenics, Inc. P. Moore, E. Bonvini: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: MacroGenics, Inc. B.J. Sumrow: Shareholder/Stockholder/Stock options, Full/Part-time employment: MacroGenics, Inc. J.J. Luke: Advisory/Consultancy: TTC Oncology; Advisory/Consultancy: 7 Hills; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Alphamab Oncology; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Pyxis; Advisory/Consultancy, Research grant/Funding (institution): Spring bank; Advisory/Consultancy: Tempest; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Travel/Accommodation/Expenses: Akrevia; Advisory/Consultancy, Research grant/Funding (institution): Algios; Advisory/Consultancy, Research grant/Funding (institution): Array; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: EMD Serono; Advisory/Consultancy: Ideava; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Mersana; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: PTx; Advisory/Consultancy, Travel/Accommodation/Expenses: RefleXion; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Rubius; Advisory/Consultancy: Silicon; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Advisory/Consultancy: Vividion; Research grant/Funding (institution): MacroGenics; Advisory/Consultancy: Arch Oncology.

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Proffered Paper - Investigational immunotherapy Proffered Paper session

1021O - Safety and antitumor activity of AK104, a bispecific antibody targeting PD-1 and CTLA-4, in patients with mesothelioma which is relapsed or refractory to standard therapies

Presentation Number
1021O
Lecture Time
15:21 - 15:33
Speakers
  • Michael Millward (Nedlands, WA, Australia)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05

Abstract

Background

Mesothelioma patients (pts) have a poor prognosis with limited treatment options. Platinum/pemetrexed chemotherapy is standard, although a phase 3 trial evaluating nivolumab plus ipilimumab in previously untreated pts with malignant pleural mesothelioma (MPM) recently disclosed statistically significant improvement in overall survival (OS) compared to chemotherapy. Furthermore, dual blockade of PD-1 and CTLA-4 in pts with recurrent MPM can result in improved disease control (DCR at 12 weeks 50%) but are limited by high rates of toxicity (26% Grade 3-4 treatment-related adverse events [TRAE]). Here, we present initial safety and efficacy data for AK104, a bispecific antibody targeting PD-1 and CTLA-4, in mesothelioma pts who have failed prior systemic therapies.

Methods

Pts with mesothelioma relapsed or refractory to at least first line chemotherapy were enrolled in an ongoing phase 1a/1b study of AK104-101 in advanced solid tumors (NCT03261011). Tumor assessments based on RECIST 1.1 were performed once every 2 cycles/8 weeks.

Results

As of 06 May 2020, 18 mesothelioma pts have been enrolled. Tumor assessment data was available for 13 pts enrolled in dose escalation cohorts at 4 mg/kg, 6 mg/kg, 10 mg/kg and 450 mg AK104 Q2W IV (28-day cycles), of which 12 were naïve to prior anti-PD-(L)1 therapy while 1 had prior anti-PD-1 treatment. Confirmed objective response rate (ORR) was 15.4% (2/13; duration of response [DoR]: 3.6+ and 12.9 months) and DCR at 8 weeks was 84.6% (11/13). Tumor shrinkage was observed in 7 pts (53.8%). Progression free survival at 6 months was 64.5%. Duration of stable disease for the pt (6mg/kg Q2W) who had prior anti-PD-1 therapy was 7.2 months. Three out of 18 pts (16.7%) had a Grade 3-4 TRAE (fever, type 1 diabetes mellitus and infusion-related reaction [IRR]); and another 9 subjects experienced Grade 1-2 TRAEs. Most commonly reported TRAEs were rash in 6 pts and IRRs in 5 pts (Grade 1-2 in 4 pts).

Conclusions

The initial results from Study AK104-101 suggest that AK104 is well-tolerated and possesses encouraging antitumor activity against mesothelioma. AK104 for the treatment of mesothelioma should be further evaluated.

Clinical trial identification

NCT03261011.

Legal entity responsible for the study

Akesobio Australia Pty Ltd.

Funding

Akesobio Australia Pty Ltd.

Disclosure

M. Millward: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Takeda. A. Prawira: Research grant/Funding (institution): Akeso Biopharma; Research grant/Funding (institution): CStone; Research grant/Funding (institution): Five Prime; Research grant/Funding (institution): Arcusbio; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Henlius; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): MSD; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Virogin; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): GSK; Research grant/Funding (institution): QBiotics. B. Tran: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution), National Coordinator for THOR study: Janssen-Cilag; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy: Tolmar; Advisory/Consultancy, Research grant/Funding (self): Ipsen; Advisory/Consultancy: IQVIA; Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (self): Pfizer; Research grant/Funding (self), Research grant/Funding (institution): Servier; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Akeso Biopharma; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Aptevo. X. Jin, B. Li, M. Wang, K.Y. Kwek: Shareholder/Stockholder/Stock options, Full/Part-time employment: Akeso Biopharma. Y. Xia: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Akeso Biopharma. J. Desai: Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy: Pierre-Fabre; Advisory/Consultancy: Eisai; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): BMS; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BeiGene. All other authors have declared no conflicts of interest.

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Proffered Paper - Investigational immunotherapy Proffered Paper session

Invited Discussant 1020O and 1021O

Lecture Time
15:33 - 15:43
Speakers
  • Maria Rescigno (Milan, Italy)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05
Proffered Paper - Investigational immunotherapy Proffered Paper session

Q&A and live discussion

Lecture Time
15:43 - 15:53
Speakers
  • Silvia Formenti (New York, United States of America)
Room
Channel 2
Date
20.09.2020
Time
14:25 - 16:05