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Displaying One Session

Mini Oral session
Date
18.09.2020
Chairs
  • Charlie Gourley (Edinburgh, United Kingdom)
  • David Cibula (Prague, Czech Republic)
  • Mansoor Raza Mirza (Copenhagen, Denmark)
Mini Oral - Gynaecological cancers 2 Mini Oral session

Open & welcome

Speakers
  • Mansoor Raza Mirza (Copenhagen, Denmark)
Mini Oral - Gynaecological cancers 2 Mini Oral session

812MO - Maintenance olaparib + bevacizumab (bev) in patients (pts) with newly diagnosed advanced high-grade ovarian cancer (HGOC): RECIST and/or CA-125 objective response rate (ORR) in the phase III PAOLA-1 trial

Presentation Number
812MO
Speakers
  • Nicoletta Colombo (Milan, Italy)

Abstract

Background

PAOLA-1/ENGOT-ov25 (NCT02477644) is a phase III trial in pts with newly diagnosed, FIGO stage III‒IV HGOC. Adding olaparib to maintenance bev after first-line platinum-based chemotherapy + bev led to a statistically significant progression-free survival (PFS) benefit in pts with advanced HGOC (hazard ratio 0.59; 95% confidence interval 0.49–0.72; P<0.001) (Ray-Coquard et al. NEJM 2019). Recently, the FDA approved olaparib + bev maintenance following first-line platinum-based chemotherapy response in homologous recombination deficiency (HRD) positive pts. We explored ORR for pts with residual disease in PAOLA-1.

Methods

Pts with no evidence of disease or clinical complete response (CR) or partial response (PR) after platinum-based chemotherapy + bev received olaparib tablets (300 mg bid for up to 24 months) + bev (15 mg/kg q3w for 15 months in total) or placebo + bev. In pts with evidence of disease (target and/or non-target lesions) and/or cancer antigen-125 (CA-125) ≥2 x upper limit at baseline (assessment following initial therapy), we explored ORR according to GCIG criteria (Rustin at al. IJGC 2011).

Results

Of 806 randomised pts, 216 (27%) had evidence of disease and/or CA-125 ≥2 x upper limit at baseline (Table). RECIST and/or CA-125 ORR was improved with olaparib + bev vs placebo + bev, with the greatest benefit seen in BRCAm pts and in HRD-positive pts (Table).

N (%) BRCAm population HRD-positive population ITT population
O + B (n=157) P + B (n=80) O + B (n=255) P + B (n=132) O + B (n=537) P + B (n=269)
Evidence of disease (target/non-target lesions) at baseline 28 (18) 19 (24) 49 (19) 32 (24) 129 (24) 73 (27)
Best overall RECIST response CR PR SD 16 (57) 2 (7) 7 (25) 5 (26) 3 (16) 9 (47) 21 (43) 5 (10) 20 (41) 7 (22) 3 (9) 18 (56) 32 (25) 7 (5) 61 (47) 13 (18) 5 (7) 40 (55)
RECIST ORR 18 (64) 8 (42) 26 (53) 10 (31) 39 (30) 18 (25)
Elevated CA-125 at baseline* 6 (4) 5 (6) 10 (4) 8 (6) 28 (5) 17 (6)
CA-125 ORR 5 (83) 3 (60) 7 (70) 5 (63) 10 (36) 5 (29)
Total evaluable population 29 (18) 20 (25) 51 (20) 35 (27) 138 (26) 78 (29)
ORR according to RECIST and/or CA-125 23 (79) 10 (50) 32 (63) 14 (40) 48 (35) 22 (28)

*At least twice upper limit; B, bevacizumab; ITT, intent to treat; O, olaparib; PD, progressive disease; SD, stable disease.

Conclusions

In PAOLA-1, maintenance bev alone achieves a substantial ORR in pts with residual disease after initial therapy. Adding olaparib improved ORRs compared with bev. In both maintenance arms, BRCAm and HRD-positive pts are deriving the greatest benefit.

Clinical trial identification

NCT02477644.

Editorial acknowledgement

Medical writing support was provided by Catherine Risebro, PhD, and Claire Routley, PhD, of Mudskipper Business Limited.

Legal entity responsible for the study

ARCAGY Research.

Funding

ARCAGY Research, AstraZeneca, Merck & Co., and F. Hoffmann-La Roche.

Disclosure

N. Colombo: Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Tesaro; Advisory/Consultancy: BioCad; Advisory/Consultancy: GSK. J. Gantzer: Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Chugai. B. Ataseven: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Honoraria (self): Celgene; Honoraria (self): Clovis Oncology; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: PharmaMar. G. Scambia: Speaker Bureau/Expert testimony: Clovis Oncology Italy S.r.l; Speaker Bureau/Expert testimony: MSD Italia S.r.l. A. Herrero: Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK/Tesaro. P. Sevelda: Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Roche. P. Vuylsteke: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: PharmaMar. P. Buderath: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: Tesaro; Travel/Accommodation/Expenses: PharmaMar. C. Pisano: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK/Tesaro. A. El-Balat: Honoraria (self), Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Olympus; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Teva. I.L. Ray-Coquard: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Agenus; Honoraria (self), Advisory/Consultancy: Advaxis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Mersena; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sereno; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis; Advisory/Consultancy: Roche/Genentech; Non-remunerated activity/ies: GINECO; Non-remunerated activity/ies: ENGOT; Non-remunerated activity/ies: GCIG; Non-remunerated activity/ies: European Community; Non-remunerated activity/ies: ESMO; Non-remunerated activity/ies: ASCO; Non-remunerated activity/ies: ESGO; Non-remunerated activity/ies: IGSC; Non-remunerated activity/ies: Inca. Swiss; Non-remunerated activity/ies: Italian, Belgium and German health authorities. All other authors have declared no conflicts of interest.

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Mini Oral - Gynaecological cancers 2 Mini Oral session

814MO - Phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): Initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC)

Presentation Number
814MO
Speakers
  • Yvette Drew (Newcastle-upon-Tyne, United Kingdom)

Abstract

Background

Olaparib is a PARP inhibitor approved in first-line and recurrent OC. Results of O+D in gBRCAm PSR OC have been presented. MEDIOLA (NCT02734004) then evaluated combining O+D (doublet cohort) or O+D+B (triplet cohort) in non-gBRCAm PSR OC. Here we present initial results.

Methods

Pts had confirmed non-gBRCAm PSR OC and had progressed after receiving 1–2 prior lines (L) of platinum-based chemotherapy. Pts received O 300 mg bid and D 1.5g IV q4 weeks (w) and B 10 mg/kg q2w (triplet only) until progressive disease. Tumours were assessed by RECIST v1.1 at baseline and q8w. Primary endpoints were safety and 24-w disease control rate (DCR). Secondary endpoints included objective response rate (ORR), median duration of response (mDOR) and progression-free survival (PFS).

Results

From Nov 2018 to Feb 2019, 32 pts (69% 2nd L) enrolled and received O+D; from May 2018 to Jan 2019, 31 (68% 2nd L) enrolled and received O+D+B. At the data cut-off 13 Feb 2020, 22% of O+D and 42% of O+D+B pts remained on treatment. The most common grade ≥3 AEs in O+D were anaemia, lipase increased and neutropenia and anaemia, hypertension, fatigue, lipase increased, and neutropenia in O+D+B. Two (6%) and five (16%) pts discontinued one or more study drug due to an AE in O+D and O+D+B, respectively. Efficacy is summarized in the table. Efficacy in biomarker subgroups, including by presence of genome-wide loss of heterozygosity, will be presented.

Non-gBRCAm PSR OC Doublet cohort (O+D) n=32 Triplet cohort (O+D+B) n=31
24-w DCR, % 28.1% (90% CI 15.5–43.9) 77.4% (90% CI 61.7–88.9)
Confirmed ORR, % 31.3% (95% CI 16.1–50.0) 77.4% (95% CI 58.9–90.4)
Median confirmed DOR (mo) 6.9 (IQR 5.7–11.1) 11.1 (IQR 9.0–16.4)
Median PFS (mo) 5.5 (95% CI 3.6–7.5) 14.7 (95% CI 10.0–18.1)

CI, confidence interval; IQR, interquartile range.

Conclusions

Combining O+D and O+D+B was well tolerated in pts with non-gBRCAm PSR OC, consistent with the known safety profiles of the single agents. The DCR for the doublet cohort did not meet the prespecified target of 80%. The 95% CI for DCR in the triplet cohort included the prespecified target of 80%. ORR and PFS in the triplet cohort demonstrate promising activity in non-gBRCAm PSR OC, and in this group the ORR and PFS are higher than reported for single-agent PARP or VEGF inhibitors.

Clinical trial identification

NCT02734004.

Editorial acknowledgement

Medical writing assistance was provided by Elin Pyke, MChem, from Mudskipper Business, Ltd, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y. Drew: Honoraria (self), Honoraria (institution), Advisory/Consultancy: AstraZeneca. R.T. Penson: Honoraria (institution), Advisory/Consultancy: AstraZeneca. D.M. O'Malley: Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Clovis; Honoraria (self), Honoraria (institution): Tesaro & Immunogen; Honoraria (self): Ambry; Honoraria (self), Honoraria (institution): Janssen/J&J; Honoraria (self), Honoraria (institution): AbbVie; Honoraria (self), Honoraria (institution): Regeneron; Honoraria (self), Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution): Novocure; Honoraria (self), Honoraria (institution): Genentech/Roche; Honoraria (institution): VentiRx; Honoraria (institution): Array Biopharma; Honoraria (institution): EMD Serono; Honoraria (institution): Ergomed; Honoraria (institution): Ajinmoto Inc; Honoraria (institution): Ludwig Cancer Research; Honoraria (institution): Stemcentrx, Inc.; Honoraria (institution): Cerulean Pharma; Honoraria (self), Honoraria (institution): GOG Foundation; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Serono Inc.; Honoraria (institution): Tracon Pharmaceuticals; Honoraria (institution): Yale University; Honoraria (institution): New Mexico Cancer Care Alliance; Honoraria (institution): INC Research, Inc.; Honoraria (institution): inVentiv Health Clinical; Honoraria (institution): Iovance Biotherapeutics, Inc.; Honoraria (institution): PRA International; Honoraria (self): Myriad Genetics, Tarveda; Honoraria (self), Honoraria (institution): Eisai, Agenus, GSK, Merck. S. Zimmermann: Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self), Non-remunerated activity/ies: Eli Lilly; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: MSD; Honoraria (self), Non-remunerated activity/ies: Novartis; Non-remunerated activity/ies: Amgen; Non-remunerated activity/ies: Astellas; Spouse/Financial dependant: Merck KGaA; Non-remunerated activity/ies: Vifor. P. Roxburgh: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (self): GlaxoSmithKline; Honoraria (institution): Tesaro. B. You: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca. S. Domchek: Honoraria (self): AstraZeneca; Honoraria (self): Clovis; Honoraria (self): Bristol-Myers Squibb. H. Gao: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. H. Angell: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. K. Meyer: Research grant/Funding (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. L. Opincar: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. L. Ottesen: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. D.O. Koralek: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. S. Banerjee: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. All other authors have declared no conflicts of interest.

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Mini Oral - Gynaecological cancers 2 Mini Oral session

Invited Discussant 812MO and 814MO

Speakers
  • Charlie Gourley (Edinburgh, United Kingdom)
Mini Oral - Gynaecological cancers 2 Mini Oral session

815MO - The impact of chemosensitivity assessed by modeled CA-125 KELIM on the likelihood of long progression-free survivorship (PS) after 1st line treatment in ovarian cancer: An analysis of 4,450 patients

Presentation Number
815MO
Speakers
  • Benoit You (Pierre BĂ©nite, CEDEX, France)

Abstract

Background

Primary tumor chemosensitivity plays an important but poorly understood role in the ovarian cancer patient prognosis. The modeled CA-125 kinetic parameter (KELIM) is an indicator of chemosensitivity, and is associated with survival (Clin Cancer Res 2019 & 2020; JNCI CS 2020). The objective was to assess the role of KELIM regarding the probability of long progression-free survivorship (PS) > 5 years after 1st line treatment.

Methods

The datasets from 3 phase III trials in adjuvant setting (AGO-OVAR 9; AGO-OVAR 7 and ICON 7) were analyzed to explore the prognostic role of KELIM regarding the probability of PS in 2,868 stage (st) I-IV patients. An independent population-based cohort of 1,582 st II-IV patients in neo-adjuvant setting from The Netherlands Cancer Registry (NCR) was used as a validation dataset.

Results

Of 2,868 patients in the learning set (median 45-month follow-up), 82 patients (2.8%) were PS: 48 st I-II (PS probability (PSp) = 9.5%); 32 st III (PSp = 1.6%); 2 st IV (PSp = 0.5%). With favorable KELIM > 0.06 days-1, PSp increased to 12.0% for st I-II, 2.9% for st III & 2.1% for st IV. In multivariable logistic regression, higher FIGO stage (st I-II reference; st III, OR = 0.18 and st IV: OR = 0.06) and KELIM (OR = 2.35 [1.51-3.59]) were predictors of PS. Of 1,582 patients in the NCR dataset (median 95-month follow-up), 36 patients (2.7%) were PS: 2 st II (PSp = 22.2%); 26 st III (PSp = 2.8%); 8 st IV (PSp = 1.2%). With favorable KELIM, PSp increased to 5.4% for st III, and 2.4% for st IV. In multivariable regression, completeness of interval debulking surgery (OR = 6.25 [2.40-21.41]) and KELIM (OR = 3.82 [1.49-9.65]) were predictors of PS. PSp was 12% for st III with favorable KELIM and complete surgery. In an explorative set with 509 patients, the KELIM prognostic impact was more marked in BRCA wild-type and BRCA1 mutated patients, than in BRCA2.

Conclusions

KELIM is an independent prognostic factor of progression-free survivorship > 5 years after 1st line treatment. The PSp is doubled in patients with favorable KELIM. The respective impacts of chemosensitivity and surgery relative to chance of potential cure are better understood.

Legal entity responsible for the study

The authors.

Funding

Dutch Cancer Society [IKNL2014-6838].

Disclosure

B. You: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy: Bayer; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Amgen; Advisory/Consultancy: MSD; Advisory/Consultancy: ECS Progastrin. R. Kruitwagen: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche. A. du Bois: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy: Clovis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Biocad; Advisory/Consultancy: Genmab/ Seattle Genetics; Advisory/Consultancy: MSD. F. Selle: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AZ; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: GSK; Honoraria (self), Speaker Bureau/Expert testimony: Clovis; Honoraria (self), Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: MSD. All other authors have declared no conflicts of interest.

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Mini Oral - Gynaecological cancers 2 Mini Oral session

816MO - AGO DESKTOP III/ENGOT OV20: Impact of surgical characteristics and time to first subsequent therapy (TFST)

Presentation Number
816MO
Speakers
  • Fabrice Lecuru (Paris, France)

Abstract

Background

DESKTOP III has shown a significant benefit regarding PFS and OS in favor of patients with secondary cytoreductive surgery compared to chemotherapy alone. This benefit seems to be limited to patients with complete cytoreduction. The reason for limited outcome in patients with suboptimal surgery could be residual disease, peri-operative characteristics or tumor biology. While TFST is an often-used parameter in oncologic trials, its role in surgical trials is not defined.

Methods

Analysis of characteristics of surgery and systemic treatment, surgical complications, and tumor biology as predictive and prognostic factors. For this analysis, patients were splitted into 3 subgroups: (1) Control arm vs (2) surgical arm but no complete resection vs (3) surgical arm and complete resection.

Results

Group 1 included 201 patients, group 2 included 65 of (46 with documented tumor residuals after surgery, 16 without surgery, 3 without data about residuals) and group 3 included 141 patients. The use of platinum-based chemotherapy was 90% in group 1 vs 83.1% in group 2 and 91.5% in group 3. The use of bevacizumab was about 23% and PARP-inhibitors in < 10% in all groups. Median duration of surgery was 204 minutes in group 2 and 230 minutes in group 3. Time from randomization to start of systemic therapy was 15 days in group 1 vs 51 and 53 days in group 2 and 3, respectively. The re-laparotomy rate was about 3% in group 2 and 3. 30-day mortality rate was 0 in all arms. TFST in the surgical arm was significantly longer compared to the non-surgical arm (16.0 vs 21.3 months; p<0.001). TFST in group 1 vs 2 vs 3 was 16.0 vs 16.1 vs 26.3 months, respectively (p<0.001).

Conclusions

Suboptimal surgery seems to have similar burden as complete resection. Therefore, preoperative selection in an experienced Gynecologic Oncology center is indicated to avoid suboptimal debulking. TFST is prolonged substantially by complete resection.

Clinical trial identification

NCT01166737.

Legal entity responsible for the study

AGO Study Group.

Funding

ARCAGY-GINECO.

Disclosure

F. Lecuru: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis Oncology. A. du Bois: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Genmab; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Advisory/Consultancy: BioCad; Advisory/Consultancy: Ingress Health; Advisory/Consultancy: TLC Biopharmaceuticals. J. Sehouli: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novocure; Travel/Accommodation/Expenses: Olympus; Honoraria (self), Advisory/Consultancy: Johnson & Johnson; Travel/Accommodation/Expenses: Roche Pharma AG; Honoraria (self): Eisai; Honoraria (self): Olympus Medical Systems; Honoraria (self): Teva; Honoraria (self): GlaxoSmithKline; Honoraria (self), Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Roche. I.B. Vergote: Advisory/Consultancy: PharmaMar; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): Genmab; Advisory/Consultancy: Millennium; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Immunogen; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Oncoinvent; Advisory/Consultancy: Sotio; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Carrick Therapeutics; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Medical University of Vienna; Advisory/Consultancy: Octimet; Travel/Accommodation/Expenses: MSD/Merck. G. Ferron: Advisory/Consultancy: Olympus; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: GlaxoSmithKline/Tesaro; Travel/Accommodation/Expenses: Roche Pharma AG; Travel/Accommodation/Expenses: PharmaMar. W. Meier: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Roche. S. Greggi: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. F. Selle: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Tesaro; Honoraria (self), Speaker Bureau/Expert testimony: GlaxoSmithKline; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: PharmaMar; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self): Clovis Oncology. C. Pomel: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: Clovis Oncology. E.H. Avall-Lundqvist: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Genmab; Honoraria (self): Roche. J. Ponce: Advisory/Consultancy: Medtronic; Advisory/Consultancy: Abex; Advisory/Consultancy: KCI. F. Raspagliesi: Advisory/Consultancy: Tesaro-GSK; Travel/Accommodation/Expenses: Roche. G-M. Sadaf: Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Johnson & Johnson. A. Reinthaller: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: PharmaMar; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Tesaro; Honoraria (self): Novartis; Honoraria (self): GlaxoSmithKline; Honoraria (self): Amgen. P. Harter: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Advisory/Consultancy: Merck; Honoraria (self): Clovis Oncology; Honoraria (self): Stryker; Honoraria (self): MSD Oncology; Honoraria (self): Zai Lab; Honoraria (self): Lilly; Honoraria (self): Sotio; Research grant/Funding (institution): Genmab. All other authors have declared no conflicts of interest.

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Mini Oral - Gynaecological cancers 2 Mini Oral session

Invited Discussant 815MO and 816MO

Speakers
  • David Cibula (Prague, Czech Republic)
Mini Oral - Gynaecological cancers 2 Mini Oral session

LBA34 - Single-agent anti-PD-1 balstilimab or in combination with anti-CTLA-4 zalifrelimab for recurrent/metastatic (R/M) cervical cancer (CC): Preliminary results of two independent phase II trials

Presentation Number
LBA34
Speakers
  • David M. O'Malley (Columbus, United States of America)

Abstract

Background

Second line treatment for R/M CC continues to be a high unmet clinical need. We present data from 2 ph2 trials, of single-agent balstilimab (bal) and in combination with zalifrelimab (zal) in R/M CC.

Methods

Patients received single-agent bal 3mg/kg q2w (NCT03104699) or in combination with zal 1mg/kg q6w (NCT03495882) up to 2 yrs. The primary endpoint was objective response rates (ORR) assessed per RECIST 1.1 by independent review, secondary endpoints included safety and DOR.

Results

We treated161 & 155 pts in the bal and bal/zal, respectively with 160 & 143 pts had baseline measurable disease (modified ITT population). All pts previously received platinum-based treatment for their first line as per protocol. Squamous-cell cancer (SCC) (63% bal; 74% bal/zal) was the predominant histologic subtype with adenocarcinoma/adenosquamous/other (AC) also represented. PD-L1 positive was defined as CPS ≥ 1% (62% bal; 55% bal/zal), negative as CPS <1% (26% bal; 25% bal/zal) or unknown (12% bal; 20% bal/zal). Efficacy data are below.

Treatment was well tolerated in both trials. 49 (30%) pts had immune-related AEs in bal & 50 (35%) in bal/zal trial (all grades) and severe (Grade 3+) 13 (8.0%) and 15 (10.5%) respectively. Treatment discontinuation were seen in 22 pts (13.7%) in bal and 15 pts (10%) in bal/zal. There were no treatment related deaths on the bal trial and 2 in the bal/zal trial (nephritis; pneumonitis). No new safety signals were identified.

Efficacy bal (160) N (%) bal/zal (143) N (%)
ORR 24 (14) 31 (22)
CR 3 (2) 8 (6)
PR 20 (12) 23 (16)
DOR (m) 15.4 [1.1+,15.4] NR [1.3+,16.6+]
SCC 18/100 (18) 28/106 (27)
AC 5/59 (8) 3/37 (7)
PD-L1 + 19/99 (19) 21/79 (27)
PD-L1 - 4/42 (10) 4/36 (11)
Unknown PD-L1 0/19 (0) 6/28 (21)

Conclusions

These results show that both single-agent bal and bal/zal are active and well tolerated in R/M CC. Adding bal to zal increased both ORR and DOR with marginal increase in AEs. Responses were more common in the PD-L1 + and SCC pts, but responses were seen in PD-L1-, AC pts. This is by far the largest reported study of checkpoint inhibitors in cervical cancer to date.

Clinical trial identification

NCT03104699, NCT03495882.

Legal entity responsible for the study

Agenus Inc.

Funding

Agenus Inc.

Disclosure

D.M. O'Malley: Honoraria (institution): AstraZeneca; Research grant/Funding (self): Clovis; Honoraria (self): Tesaro; Honoraria (self), Honoraria (institution): Immunogen; Honoraria (self): Ambry; Honoraria (self), Honoraria (institution): Jansen/J&J; Honoraria (self), Honoraria (institution): AbbVie; Honoraria (self), Honoraria (institution): Regeneron; Honoraria (self), Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution): Novocure; Honoraria (self), Honoraria (institution): Genentech/Roche; Honoraria (institution): VentiRx; Honoraria (institution): Array Biopharma; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Ergomed; Research grant/Funding (institution): Ajinomoto Inc.; Research grant/Funding (institution): Stemcentrx, Inc.; Research grant/Funding (institution): Cerulean Pharma; Honoraria (self), Research grant/Funding (institution): GOG Foundation; Research grant/Funding (institution): Bristol-Myers Squibb Co; Research grant/Funding (institution): Serono Inc; Research grant/Funding (institution): Tracon Pharmaceuticals; Research grant/Funding (institution): Yale University; Research grant/Funding (institution): New Mexico Cancer Care Alliance; Research grant/Funding (institution): INC Research, Inc; Research grant/Funding (institution): inVentiv Health Clinical; Research grant/Funding (institution): Iovance Biotherapeutics, Inc; Research grant/Funding (institution): PRA Int; Honoraria (self): Myriad Genetics; Honoraria (self), Research grant/Funding (institution): Esai. I.L. Ray-Coquard: Honoraria (self), Advisory/Consultancy: Agenus Inc.; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: advaxis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Mersena; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis. All other authors have declared no conflicts of interest.

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Mini Oral - Gynaecological cancers 2 Mini Oral session

LBA35 - Phase II study of PARP inhibitor talazoparib and PD-L1 inhibitor avelumab in patients (pts) with microsatellite stable (MSS) recurrent/persistent endometrial cancer

Presentation Number
LBA35
Speakers
  • Panagiotis A. Konstantinopoulos (Boston, United States of America)

Abstract

Background

Preclinical studies have demonstrated synergistic antitumor activity for combinations of PARP inhibitors (PARPi) with PD-1/PD-L1 inhibitors (PD-1/PD-L1i) which is at least partly mediated by activation of the Stimulator of Interferon Genes (STING) pathway. Given that PD-1/PD-L1i exhibit only modest activity as monotherapy against MSS endometrial cancer (EC), we evaluated whether the combination of the PARPi talazoparib and the PD-L1i avelumab would demonstrate promising activity and acceptable toxicity in that setting.

Methods

We conducted a single-arm phase 2 study to evaluate avelumab and talazoparib in recurrent MSS EC (MSS determined by IHC). Eligibility criteria included measurable disease, no limit on prior therapies, and all EC histologies including carcinosarcomas. Co-primary endpoints were objective response rate (ORR) by RECIST 1.1 and progression-free survival rate at 6 months (PFS6). Talazoparib 1mg PO daily and avelumab 10 mg/kg IV every 2 weeks were administered until progression or unacceptable toxicity. A two-stage design was employed to allow for early stopping for futility. In the 1st stage, 16 pts were enrolled; if there were ≥2 ORs or ≥2 PFS6 responses, accrual would continue to the 2nd stage with enrollment of 19 additional pts. Overall, if there were ≥4 ORs or ≥8 PFS6 responses, avelumab+talazoparib would be considered worthy of further study.

Results

As of June, 5th 2020, 35 pts initiated therapy. Three pts exhibited OR [3PRs, ORR 8.6% (95% CI 1.8%-23.1%)] and 8 exhibited PFS6 responses (PFS6 responses by histology: 3 endometrioid, 3 serous, 1 clear cell and 1 carcinosarcoma), 5 ongoing. PFS at 6 months was 25.8% (95% CI 12.4%-41.4%) and median PFS was 3.65 months (95% CI: 2.4-5.4 months). Most common G3+ treatment-related toxicities were anemia (n=16, 45.7%), thrombocytopenia (n=10, 28.6%) and neutropenia (n=4, 11.4%). Seven (20%) pts had dose reductions; no pt discontinued therapy because of toxicity.

Conclusions

Avelumab and talazoparib met the predetermined PFS6 response criterion to be considered worthy of further evaluation in this pt population of recurrent MSS EC. Correlation with biomarkers of response to PARPi and PD-1/PD-L1i is ongoing.

Clinical trial identification

NCT02912572.

Legal entity responsible for the study

Panagiotis Konstantinopoulos.

Funding

Pfizer.

Disclosure

P.A. Konstantinopoulos: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Tesaro/GSK; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Alkermes; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): Eli Lilly. J.F. Liu: Advisory/Consultancy, Research grant/Funding (institution): Tesaro/GSK; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Genentech; Research grant/Funding (institution): 2X Oncology; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): Arch Oncology; Research grant/Funding (institution): Bristol Myers Squibb; Research grant/Funding (institution): CytoMX Therapeutics; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Surface Oncology; Research grant/Funding (institution): Vigeo Therapeutics. R.T. Penson: Advisory/Consultancy, Also participation in DSMB: AbbVie; Advisory/Consultancy, Research grant/Funding (institution), Also participation in DSMB: AstraZeneca; Advisory/Consultancy: Clovis; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Janssen Oncology (J&J); Advisory/Consultancy: Merck & Co; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: Pieris Pharma Inc; Advisory/Consultancy: Roche; Advisory/Consultancy: Sutro Biopharma; Advisory/Consultancy: Syndax Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Vascular Biogenics Ltd.; Research grant/Funding (institution): Array BioPharma Inc.; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Sanofi-Aventis US Llc. G. Fleming: Honoraria (self): Curio Science; Advisory/Consultancy: GSK; Research grant/Funding (institution), Research IP Supply: Corcept; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Tesaro/GSK; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): 47inc; Research grant/Funding (institution): Iovance; Research grant/Funding (institution): Syros; Research grant/Funding (institution): Astex; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Compugen; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Eisai. U.A. Matulonis: Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: AstraZeneca. All other authors have declared no conflicts of interest.

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Mini Oral - Gynaecological cancers 2 Mini Oral session

LBA36 - Safety and antitumor activity of dostarlimab in patients (pts) with advanced or recurrent DNA mismatch repair deficient (dMMR) or proficient (MMRp) endometrial cancer (EC): Results from GARNET

Presentation Number
LBA36
Speakers
  • Ana Oaknin (Barcelona, Spain)

Abstract

Background

Dostarlimab (TSR-042) is a humanized programmed death (PD)-1 receptor monoclonal antibody that blocks interaction with the PD-1 ligands. GARNET is a phase I study assessing antitumor activity and safety of dostarlimab monotherapy in pts with solid tumors.

Methods

This multicenter, open-label, single-arm study includes dose escalation and expansion parts. Here we report on 2 independent expansion cohorts of pts with recurrent or advanced EC (dMMR EC and MMRp EC, determined by immunohistochemistry [IHC]) that progressed on or after a platinum-based chemotherapy regimen. Pts received 500 mg dostarlimab IV Q3W for 4 cycles, then 1000 mg Q6W until disease progression, discontinuation, or withdrawal. The primary endpoints are objective response rate (ORR) and duration of response (DOR) by blinded independent central review using RECIST v1.1.

Results

In total, 126 dMMR and 145 MMRp pts identified by IHC were enrolled and dosed. Of these, 103 and 142 pts had sufficient follow-up time (24 wks) for efficacy analyses, respectively. dMMR ORR was 44.7%; MMRp ORR was 13.4% (Table). Median DOR and OS were not reached. The most common grade ≥3 TEAEs (N=271) were anemia (12.2%), abdominal pain (4.8%), and dyspnea (4.1%). The most common grade ≥3 immune-related TEAEs were diarrhea, aspartate aminotransferase increased, and alanine aminotransferase increased (1.8% each). There were no treatment-related deaths.

Conclusions

Dostarlimab demonstrated durable antitumor activity in both dMMR and MMRp advanced/recurrent EC. dMMR status by IHC was associated with a higher response rate. No new safety signals were detected. These cohorts are the largest prospective evaluation of a PD-(L)1 therapy in EC to date.

Variable, unit dMMR N=103 MMRp N=142
Median follow-up, mo 16.3 11.5
ORR, n (% [95% CI]) Complete response, n (%) Partial response, n (%) Stable disease, n (%) 46 (44.7 [34.9–54.8]) 11 (10.7) 35 (34.0) 13 (12.6) 19 (13.4 [8.3–20.1]) 3 (2.1) 16 (11.3) 31 (21.8)
Disease control rate, n (% [95% CI]) 59 (57.3 [47.2–67.0]) 50 (35.2 [27.4–43.7])
Response ongoing, n (%) 41 (89.1) 12 (63.2)
18 mo DOR, % (95% CI) 79.2 (54.9–91.3) 61.3 (32.5–80.8)

Clinical trial identification

NCT02715284.

Editorial acknowledgement

Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Back, PhD of GlaxoSmithKline was provided by Nicole Renner, PhD and Anne Cooper of Ashfield Healthcare Communications (Middletown, CT, USA).

Legal entity responsible for the study

GlaxoSmithKline, Waltham, MA, USA.

Funding

GlaxoSmithKline, Waltham, MA, USA.

Disclosure

A. Oaknin: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Tesaro; Honoraria (institution), Advisory/Consultancy: Clovis; Honoraria (institution), Advisory/Consultancy: PharmaMar; Honoraria (institution), Advisory/Consultancy: Roche. L. Gilbert: Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer. A.V. Tinker: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca. R. Sabatier: Research grant/Funding (institution): Eisai; Advisory/Consultancy, Non-remunerated activity/ies: Roche; Advisory/Consultancy, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Novartis; Advisory/Consultancy, Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Amgen. D.M. O'Malley: Advisory/Consultancy: Tesaro, Immunogen, Eisai, Agenus, GSK; Advisory/Consultancy: Clovis, Ambry, AbbVie; Advisory/Consultancy: Janssen/J&J, Regeneron, Novacure, Myraid Genetics, Tarveda; Advisory/Consultancy: Amgen; Advisory/Consultancy: Genentech/Roche, Merck; Research grant/Funding (institution): VentiRx, Array Biopharma, EMD Serono, Ergomed; Research grant/Funding (institution): Ajinomoto Inc, Ludwig Cancer Research; Research grant/Funding (institution): Stemcentrx, Inc, Cerulean Pharma, GOG Foundation; Research grant/Funding (institution): BMS, Serono Inc, Tracon Pharmaceuticals; Research grant/Funding (institution): Yale University, New Mexico Cancer Care Alliance; Research grant/Funding (institution): INC Research, Inc., Inventiv Health Clinical; Research grant/Funding (institution): Iovance Biotherapeutics, Inc, PRA Intl. S. Ghamande: Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Tesaro; Speaker Bureau/Expert testimony, Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Advaxis; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): AbbVie. L. Duska: Research grant/Funding (institution): Merck, Genentech/Roche, GlaxoSmithKline, Inovio; Advisory/Consultancy: AstraZeneca, Genentech/Roche, MorphoTek; Advisory/Consultancy: Merck, Cue Biopharma; Licensing/Royalties: Elsevier, JB Learning. W. Guo: Full/Part-time employment: GlaxoSmithKline. E. Im: Full/Part-time employment: GlaxoSmithKline. B. Pothuri: Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Tesaro; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology. All other authors have declared no conflicts of interest.

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Mini Oral - Gynaecological cancers 2 Mini Oral session

Invited Discussant LBA34, LBA35 and LBA36

Speakers
  • Mansoor R. Mirza (Copenhagen, Denmark)