- Email: [email protected]
R DLBCL) patients after receiving immunotherapy
abstracts
Annals of Oncology
Evolution of myeloid-derived suppressor cells and objective response rate in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) patients after receiving immunotherapy
on Carri on2, E. Nogales Fernandez2, M.A. Nieto Garcıa3, C. Jime´nez Cortegana1, N. Palaz de la Gala2, M. Suengas Martınez de Ilarduya2, E. V. Sanchez Margalet1, M.D.C. Alamo Montilla Burgos2, I. Ara ujo Fernandez2, F. Henao Carrasco2, A. Martın Garcıa-Sancho4, F. Carnicero5, E. Rios Herranz6, F. de la Cruz Vicente7, R. Fernandez8, A. Rueda Dominguez9, L. de la Cruz Merino2 1 Medical Biochemistry, Virgen Macarena University Hospital, Seville, Spain, 2Medical Oncology, Virgen Macarena University Hospital, Seville, Spain, 3Preventive Medicine and Public Health, University of Seville, Seville, Spain, 4Hematology and Hemotherapy, University Hospital of Salamanca, Salamanca, Spain, 5Hematology and Hemotherapy, San Pedro de Alc antara Hospital, C aceres, Spain, 6Hematology, Virgen de Valme University Hospital, Seville, Spain, 7Hematology and Hemotherapy, Virgen del Rocıo University Hospital, Seville, Spain, 8Hematology and Hemotherapy, Hospital of alaga, Cabue~ nes, Gij on, Spain, 9Medical Oncology, Costa del Sol Hospital, Marbella, M Spain Background: Myeloid derived suppresor cells (MDSC) are a heterogeneous population of immature myeloid cells that inhibits antitumor responses by T lymphocytes. High levels of MDSC have been found in the tumor microenvironment, which is correlated with a poor prognosis of the disease. Our purposes are to evaluate the objective response rate (ORR) to test the treatment efficacy and to show the decrease of MDSC in clinical benefit (CB) patients, that includes complete response (CR), partial response (PR) and stabilization of disease (SD), when compared with progression of disease (PD). Methods: 58 patients diagnosed of R/R DLBCL who were not high dose chemotherapy and autologous bone narrow transplantation candidates were recruited from Spanish hospitals. The patients progressed to a prior R-CHOP therapy and had ECOG 1. They were treated with the R2-GDP chemotherapy schedule (rituximab, lenalidomide, gemcitabine, dexamethasone and cisplatin). Three peripheral blood analysis were carried out: basal, cycle 3 (C3) and end of induction (EI) by flow cytometry to determine the MDSC level. Results: 30 patients obtained CB response to treatment (PR 11 patients, CR 14 patients and SD 5 patients) and 28 patients obtained PD. A remarkable decrease of MDSC is shown in the Table, except in PD patients. On the other hand, ORR was 69% at C3 (PR 53%þ CR 16%) and 66% at EI (PR 40% þ CR 26%).
Table: 1267P MDSC levels (cells/uL) in CB (CR, PR, SD) and PD. Av: average; St: Standard Deviation; *: Statistically significant differences (P < 0.05) compared with basal Response
Basal Av (St)
C3 Av (St)
EI Av (St)
CB CR PR SD PD
19.9 (4.0) 18.6 (4.9) 13.0 (3.2) 35.3 (14.8) 10.7 (4.0)
10.0 (3.1) 12.4 (3.7) 4.5 (0.8) 18.8 (11.6) 8.6 (2.4)
4.8 (2.1)* 2.7 (1.1)* 1.4 (0.5)* 18.5 (9.2) 12.2 (2.9)
Conclusions: The ORR obtained shown the treatment efficacy in R/R DLBCL to stimulate the immune system antitumor response, which explains the decrease of MDSC in all CB groups and a non-important increase in PD patients. Based on these results,
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz253 | v515
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz253.092/5577612 by guest on 24 October 2019
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abstracts MDSC seem to be an important therapeutic target against tumor progression, as well as being a potentially promising marker of response. Clinical trial identification: EudraCT number: 2014-001620-29. Legal entity responsible for the study: Grupo Espa~ nol para el Tratamiento y Estudio de los Linfomas (GOTEL). Funding: Grupo Espa~ nol para el Tratamiento y Estudio de los Linfomas (GOTEL). Disclosure: All authors have declared no conflicts of interest.
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L. Shen1, J. Li2, N. Xu3, B. Xing4, Q. Zhang5, Y. Zhao6, J. Cao7, J. Ding8, J. Wang8, Y. Wang8, H. Dai8 1 Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China, 2 Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China, 3Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, 4Hepatobiliary and Pancreatic Surgery, Beijing Cancer Hospital, Beijing, China, 5Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China, 6Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China, 7Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 8Clinical and RA, CStone Pharmaceuticals (Su Zhou) Co., Ltd., Suzhou, China Background: CS1001 is a first full-length, fully human anti-PD-L1 mAb developed by the OMT transgenic rat platform, which mirrors natural IgG4 human antibody with expected pharmacokinetics (PK) profiles, and may potentially reduce the risk of immunogenicity and toxicity in pts. This first-in-human Phase Ia/Ib study of CS1001 was conducted to evaluate the safety, tolerability, PK profile, and anti-tumor activity of CS1001 in pts with advanced solid tumors or lymphomas. Methods: Pts with advanced solid tumors or lymphomas were enrolled in the dose escalation Phase Ia, receiving CS1001, Q3W, IV, at escalating doses from 3, to 10, 20, 40 mg/kg and 1200 mg fixed dose. Dose escalation followed a 3 þ 3 dose escalation scheme. Dose-limiting toxicity (DLT) was evaluated within 3 weeks after the initial dose. Pts with various tumor types were enrolled in the dose expansion Phase Ib to assess anti-tumor activity and safety, including GC, cholangiocarcinoma, NSCLC, HCC, etc. Safety was assessed by monitoring the frequency and severity of adverse events (AEs) per NCI CTCAE v4.03, tumor response was assessed per RECIST v1.1 (solid tumors) or Lugano 2014 (lymphomas). Results: As of 30 Nov 2018, 29 pts, median age of 53 (23-75) years, were enrolled in Phase Ia, 3 mg/kg (N ¼ 3); 10 mg/kg (4); 20 mg/kg (3); 40 mg/kg (3) and 1200 mg fixed dose (16). 20 pts discontinued treatment, mostly due to disease progression (14). 2 pts discontinued treatment due to AEs (Grade [G] 4 hepatic function abnormal and G3 pulmonary tuberculosis, neither of which were related to CS1001). Median treatment duration was 126 (21-408þ) days. No DLTs were observed. The most frequent TRAEs included anaemia (48.3%) and proteinuria (44.8%). SAEs were reported in 6 pts and they were not related to CS1001. irAEs occurred in 7 pts. Among the 29 pts, 7 (24%) pts had PR, mDoR was not reached. In Phase Ib, 162 pts were enrolled as of 15 Mar 2019. Conclusions: CS1001 is well tolerated without DLT across the dose levels investigated. Evidence of anti-tumor activities was observed. Currently, 1200 mg fixed dose Q3W is being explored in various tumor types in Phase Ib, safety and efficacy results of selected Phase Ib expansion arms will be reported at the conference presentation. Clinical trial identification: NCT03312842. Legal entity responsible for the study: CStone Pharmaceuticals (Su Zhou) Co., Ltd. Funding: CStone Pharmaceuticals (Su Zhou) Co., Ltd. Disclosure: J. Ding: Full / Part-time employment: CStone Pharmaceuticals. J. Wang: Full / Parttime employment: CStone Pharmaceuticals. Y. Wang: Full / Part-time employment: CStone Pharmaceuticals. H. Dai: Full / Part-time employment: CStone Pharmaceuticals. All other authors have declared no conflicts of interest.
MEDI0680 (M) and PD-1:PD-L1/CD80 with anti-PD-L1 mAb durvalumab (D) would improve efficacy vs blockade of the PD-1:PD-L1/PD-L2 pathway (with nivolumab; N) alone. MþD was well tolerated in the dose-escalation phase of a Phase I/II study in pts with advanced solid tumours, with an ORR of 33% (10/30; including 3/4 RCC pts). In the Phase II portion of the study, we compared MþD to N in a dose-expansion cohort of pretreated, immunotherapy (IO)-naı¨ve pts with metastatic ccRCC. Methods: Eligible pts had received 1–3 prior therapy lines, no prior IO exposure and 1 measurable lesion. They were randomised 2:1 (stratified by MSKCC risk group and PD-L1 expression) to M 20 mg/kg IV þ D 750 mg Q2W or N 240 mg IV Q2W until unacceptable toxicity or disease progression, for 2 years. Endpoints included investigator-assessed ORR by RECIST v1.1 (primary endpoint), PFS and safety (secondary). Sample size was 60 to detect a difference of 26.0% (ie, ORR ¼ 47.5%, assuming ORR of 21.5% for N) with 76% power at a 1-sided significance level of 0.10. Results: By Feb 24, 2019, 63 pts were randomised. Baseline pt/disease characteristics were generally well balanced, but more pts on N had favourable MSKCC risk (7/21; 33.3%) vs MþD (10/42; 23.8%). ORR was 14.3% (6/42; 2 CR, 4 PR; plus 2 unconfirmed PR) vs 19.0% (4/21; 4 PR, 0 unconfirmed) for MþD and N, respectively. There was no difference between arms in ORR by PD-L1 expression (<1% vs 1%). All responses are ongoing. Median PFS was 3.6 months in both arms. Grade 3/4 treatment-related AEs (TRAEs) occurred in 26% on MþD (including 1 case of autoimmune encephalitis) and 19% on N. On MþD, 12% had TRAEs leading to treatment discontinuation, including colitis or diarrhoea (n ¼ 3) and increased ALT/transaminases (n ¼ 2), vs 5% on N (pancreatitis and increased lipase and amylase in 1 pt). There were no Grade 5 TRAEs. Conclusions: Efficacy was similar with combined MþD and N monotherapy in pts with TKI-pretreated, IO-naı¨ve, metastatic ccRCC, but more pts discontinued MþD due to TRAEs. Clinical trial identification: NCT02118337. Editorial acknowledgement: Aaron Korpal, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: M.H. Voss: Research grant / Funding (institution): BMS; Research grant / Funding (institution): Genentech; Honoraria (self): Eisai; Honoraria (self): Exelixis; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Calithera; Honoraria (self): Corvus. A.A. Azad: Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Non-remunerated activity/ies: Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Research grant / Funding (institution), Non-remunerated activity/ies: Merck Serono; Honoraria (self), Advisory / Consultancy: Tolmar; Honoraria (self), Advisory / Consultancy, Non-remunerated activity/ies: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy: Telix Pharmaceuticals; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Sanofi. A.R. Hansen: Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): BristolMyers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boston Biomedical; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Triptych Health Partners; Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Epic Sciences; Research grant / Funding (institution): BMS; Research grant / Funding (institution): BI; Research grant / Funding (institution): Trovagene; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Novartis. I. Achour: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H. Hu: Full / Part-time employment: AstraZeneca. L. Lewis: Travel / Accommodation / Expenses, Full / Part-time employment: AstraZeneca. F.L. Walcott: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. S.F. Oosting: Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.
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Results from a randomised phase I/II trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
M.H. Voss1, A.A. Azad2, A.R. Hansen3, J.E. Gray4, S.J. Welsh5, I. Achour6, H. Hu7, L. Lewis7, F.L. Walcott7, S.F. Oosting8 1 Medicine / GU Oncology / Non-prostate, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 2Medical Oncology, Monash Health, Melbourne, Australia, 3 Hematology and Oncology, Princess Margaret Cancer Center, Toronto, ON, Canada, 4 Thoracic Oncology, H. Lee Moffitt Cancer Center University of South Florida, Tampa, FL, USA, 5Medical Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK, 6Pharmacogenomics, AstraZeneca, Gaithersburg, MD, USA, 7Clinical Development, AstraZeneca, Gaithersburg, MD, USA, 8University Medical Center Groningen, University of Groningen, Groningen, Netherlands Background: MEDI0680 is a humanised IgG4j anti-programmed cell death-1 (PD-1) mAb. We hypothesised that simultaneous blockade of PD-1:PD-L1/PD-L2 with
v516 | Immunotherapy of Cancer
Pembrolizumab in advanced rare cancers
A. Naing1, F. Meric-Bernstam1, D. Karp1, J.A. Rodon1, S.A. Piha-Paul1, V. Subbiah1, D.S. Hong1, S. Pant1, S. Fu1, F. Janku1, T.A. Yap1, A.M. Tsimberidou1, E.E. Ileana Dumbrava1, R.R. Colen2, K.R. Hess3, M.T. Campbell4, S-M. Tu4, C. Jimenez5, M.A. Habra5, G.R. Varadhachary6 1 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 3Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 4Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 5Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 6Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: Patients with rare cancers account for 25% of cancer-related deaths but have limited treatment options. As immunotherapy has potential applicability across cancer types, we conducted an open-label phase II trial of pembrolizumab in patients with advanced rare cancers.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz253.092/5577612 by guest on 24 October 2019
A phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumours or lymphomas
Annals of Oncology
Annals of Oncology
Evolution of myeloid-derived suppressor cells and objective response rate in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) patients after receiving immunotherapy
on Carri on2, E. Nogales Fernandez2, M.A. Nieto Garcıa3, C. Jime´nez Cortegana1, N. Palaz de la Gala2, M. Suengas Martınez de Ilarduya2, E. V. Sanchez Margalet1, M.D.C. Alamo Montilla Burgos2, I. Ara ujo Fernandez2, F. Henao Carrasco2, A. Martın Garcıa-Sancho4, F. Carnicero5, E. Rios Herranz6, F. de la Cruz Vicente7, R. Fernandez8, A. Rueda Dominguez9, L. de la Cruz Merino2 1 Medical Biochemistry, Virgen Macarena University Hospital, Seville, Spain, 2Medical Oncology, Virgen Macarena University Hospital, Seville, Spain, 3Preventive Medicine and Public Health, University of Seville, Seville, Spain, 4Hematology and Hemotherapy, University Hospital of Salamanca, Salamanca, Spain, 5Hematology and Hemotherapy, San Pedro de Alc antara Hospital, C aceres, Spain, 6Hematology, Virgen de Valme University Hospital, Seville, Spain, 7Hematology and Hemotherapy, Virgen del Rocıo University Hospital, Seville, Spain, 8Hematology and Hemotherapy, Hospital of alaga, Cabue~ nes, Gij on, Spain, 9Medical Oncology, Costa del Sol Hospital, Marbella, M Spain Background: Myeloid derived suppresor cells (MDSC) are a heterogeneous population of immature myeloid cells that inhibits antitumor responses by T lymphocytes. High levels of MDSC have been found in the tumor microenvironment, which is correlated with a poor prognosis of the disease. Our purposes are to evaluate the objective response rate (ORR) to test the treatment efficacy and to show the decrease of MDSC in clinical benefit (CB) patients, that includes complete response (CR), partial response (PR) and stabilization of disease (SD), when compared with progression of disease (PD). Methods: 58 patients diagnosed of R/R DLBCL who were not high dose chemotherapy and autologous bone narrow transplantation candidates were recruited from Spanish hospitals. The patients progressed to a prior R-CHOP therapy and had ECOG 1. They were treated with the R2-GDP chemotherapy schedule (rituximab, lenalidomide, gemcitabine, dexamethasone and cisplatin). Three peripheral blood analysis were carried out: basal, cycle 3 (C3) and end of induction (EI) by flow cytometry to determine the MDSC level. Results: 30 patients obtained CB response to treatment (PR 11 patients, CR 14 patients and SD 5 patients) and 28 patients obtained PD. A remarkable decrease of MDSC is shown in the Table, except in PD patients. On the other hand, ORR was 69% at C3 (PR 53%þ CR 16%) and 66% at EI (PR 40% þ CR 26%).
Table: 1267P MDSC levels (cells/uL) in CB (CR, PR, SD) and PD. Av: average; St: Standard Deviation; *: Statistically significant differences (P < 0.05) compared with basal Response
Basal Av (St)
C3 Av (St)
EI Av (St)
CB CR PR SD PD
19.9 (4.0) 18.6 (4.9) 13.0 (3.2) 35.3 (14.8) 10.7 (4.0)
10.0 (3.1) 12.4 (3.7) 4.5 (0.8) 18.8 (11.6) 8.6 (2.4)
4.8 (2.1)* 2.7 (1.1)* 1.4 (0.5)* 18.5 (9.2) 12.2 (2.9)
Conclusions: The ORR obtained shown the treatment efficacy in R/R DLBCL to stimulate the immune system antitumor response, which explains the decrease of MDSC in all CB groups and a non-important increase in PD patients. Based on these results,
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz253 | v515
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz253.092/5577612 by guest on 24 October 2019
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abstracts MDSC seem to be an important therapeutic target against tumor progression, as well as being a potentially promising marker of response. Clinical trial identification: EudraCT number: 2014-001620-29. Legal entity responsible for the study: Grupo Espa~ nol para el Tratamiento y Estudio de los Linfomas (GOTEL). Funding: Grupo Espa~ nol para el Tratamiento y Estudio de los Linfomas (GOTEL). Disclosure: All authors have declared no conflicts of interest.
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L. Shen1, J. Li2, N. Xu3, B. Xing4, Q. Zhang5, Y. Zhao6, J. Cao7, J. Ding8, J. Wang8, Y. Wang8, H. Dai8 1 Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China, 2 Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China, 3Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, 4Hepatobiliary and Pancreatic Surgery, Beijing Cancer Hospital, Beijing, China, 5Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China, 6Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China, 7Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 8Clinical and RA, CStone Pharmaceuticals (Su Zhou) Co., Ltd., Suzhou, China Background: CS1001 is a first full-length, fully human anti-PD-L1 mAb developed by the OMT transgenic rat platform, which mirrors natural IgG4 human antibody with expected pharmacokinetics (PK) profiles, and may potentially reduce the risk of immunogenicity and toxicity in pts. This first-in-human Phase Ia/Ib study of CS1001 was conducted to evaluate the safety, tolerability, PK profile, and anti-tumor activity of CS1001 in pts with advanced solid tumors or lymphomas. Methods: Pts with advanced solid tumors or lymphomas were enrolled in the dose escalation Phase Ia, receiving CS1001, Q3W, IV, at escalating doses from 3, to 10, 20, 40 mg/kg and 1200 mg fixed dose. Dose escalation followed a 3 þ 3 dose escalation scheme. Dose-limiting toxicity (DLT) was evaluated within 3 weeks after the initial dose. Pts with various tumor types were enrolled in the dose expansion Phase Ib to assess anti-tumor activity and safety, including GC, cholangiocarcinoma, NSCLC, HCC, etc. Safety was assessed by monitoring the frequency and severity of adverse events (AEs) per NCI CTCAE v4.03, tumor response was assessed per RECIST v1.1 (solid tumors) or Lugano 2014 (lymphomas). Results: As of 30 Nov 2018, 29 pts, median age of 53 (23-75) years, were enrolled in Phase Ia, 3 mg/kg (N ¼ 3); 10 mg/kg (4); 20 mg/kg (3); 40 mg/kg (3) and 1200 mg fixed dose (16). 20 pts discontinued treatment, mostly due to disease progression (14). 2 pts discontinued treatment due to AEs (Grade [G] 4 hepatic function abnormal and G3 pulmonary tuberculosis, neither of which were related to CS1001). Median treatment duration was 126 (21-408þ) days. No DLTs were observed. The most frequent TRAEs included anaemia (48.3%) and proteinuria (44.8%). SAEs were reported in 6 pts and they were not related to CS1001. irAEs occurred in 7 pts. Among the 29 pts, 7 (24%) pts had PR, mDoR was not reached. In Phase Ib, 162 pts were enrolled as of 15 Mar 2019. Conclusions: CS1001 is well tolerated without DLT across the dose levels investigated. Evidence of anti-tumor activities was observed. Currently, 1200 mg fixed dose Q3W is being explored in various tumor types in Phase Ib, safety and efficacy results of selected Phase Ib expansion arms will be reported at the conference presentation. Clinical trial identification: NCT03312842. Legal entity responsible for the study: CStone Pharmaceuticals (Su Zhou) Co., Ltd. Funding: CStone Pharmaceuticals (Su Zhou) Co., Ltd. Disclosure: J. Ding: Full / Part-time employment: CStone Pharmaceuticals. J. Wang: Full / Parttime employment: CStone Pharmaceuticals. Y. Wang: Full / Part-time employment: CStone Pharmaceuticals. H. Dai: Full / Part-time employment: CStone Pharmaceuticals. All other authors have declared no conflicts of interest.
MEDI0680 (M) and PD-1:PD-L1/CD80 with anti-PD-L1 mAb durvalumab (D) would improve efficacy vs blockade of the PD-1:PD-L1/PD-L2 pathway (with nivolumab; N) alone. MþD was well tolerated in the dose-escalation phase of a Phase I/II study in pts with advanced solid tumours, with an ORR of 33% (10/30; including 3/4 RCC pts). In the Phase II portion of the study, we compared MþD to N in a dose-expansion cohort of pretreated, immunotherapy (IO)-naı¨ve pts with metastatic ccRCC. Methods: Eligible pts had received 1–3 prior therapy lines, no prior IO exposure and 1 measurable lesion. They were randomised 2:1 (stratified by MSKCC risk group and PD-L1 expression) to M 20 mg/kg IV þ D 750 mg Q2W or N 240 mg IV Q2W until unacceptable toxicity or disease progression, for 2 years. Endpoints included investigator-assessed ORR by RECIST v1.1 (primary endpoint), PFS and safety (secondary). Sample size was 60 to detect a difference of 26.0% (ie, ORR ¼ 47.5%, assuming ORR of 21.5% for N) with 76% power at a 1-sided significance level of 0.10. Results: By Feb 24, 2019, 63 pts were randomised. Baseline pt/disease characteristics were generally well balanced, but more pts on N had favourable MSKCC risk (7/21; 33.3%) vs MþD (10/42; 23.8%). ORR was 14.3% (6/42; 2 CR, 4 PR; plus 2 unconfirmed PR) vs 19.0% (4/21; 4 PR, 0 unconfirmed) for MþD and N, respectively. There was no difference between arms in ORR by PD-L1 expression (<1% vs 1%). All responses are ongoing. Median PFS was 3.6 months in both arms. Grade 3/4 treatment-related AEs (TRAEs) occurred in 26% on MþD (including 1 case of autoimmune encephalitis) and 19% on N. On MþD, 12% had TRAEs leading to treatment discontinuation, including colitis or diarrhoea (n ¼ 3) and increased ALT/transaminases (n ¼ 2), vs 5% on N (pancreatitis and increased lipase and amylase in 1 pt). There were no Grade 5 TRAEs. Conclusions: Efficacy was similar with combined MþD and N monotherapy in pts with TKI-pretreated, IO-naı¨ve, metastatic ccRCC, but more pts discontinued MþD due to TRAEs. Clinical trial identification: NCT02118337. Editorial acknowledgement: Aaron Korpal, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: M.H. Voss: Research grant / Funding (institution): BMS; Research grant / Funding (institution): Genentech; Honoraria (self): Eisai; Honoraria (self): Exelixis; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Calithera; Honoraria (self): Corvus. A.A. Azad: Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Non-remunerated activity/ies: Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Research grant / Funding (institution), Non-remunerated activity/ies: Merck Serono; Honoraria (self), Advisory / Consultancy: Tolmar; Honoraria (self), Advisory / Consultancy, Non-remunerated activity/ies: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy: Telix Pharmaceuticals; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Sanofi. A.R. Hansen: Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): BristolMyers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boston Biomedical; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Triptych Health Partners; Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Epic Sciences; Research grant / Funding (institution): BMS; Research grant / Funding (institution): BI; Research grant / Funding (institution): Trovagene; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Novartis. I. Achour: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H. Hu: Full / Part-time employment: AstraZeneca. L. Lewis: Travel / Accommodation / Expenses, Full / Part-time employment: AstraZeneca. F.L. Walcott: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. S.F. Oosting: Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.
1270P 1269P
Results from a randomised phase I/II trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
M.H. Voss1, A.A. Azad2, A.R. Hansen3, J.E. Gray4, S.J. Welsh5, I. Achour6, H. Hu7, L. Lewis7, F.L. Walcott7, S.F. Oosting8 1 Medicine / GU Oncology / Non-prostate, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 2Medical Oncology, Monash Health, Melbourne, Australia, 3 Hematology and Oncology, Princess Margaret Cancer Center, Toronto, ON, Canada, 4 Thoracic Oncology, H. Lee Moffitt Cancer Center University of South Florida, Tampa, FL, USA, 5Medical Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK, 6Pharmacogenomics, AstraZeneca, Gaithersburg, MD, USA, 7Clinical Development, AstraZeneca, Gaithersburg, MD, USA, 8University Medical Center Groningen, University of Groningen, Groningen, Netherlands Background: MEDI0680 is a humanised IgG4j anti-programmed cell death-1 (PD-1) mAb. We hypothesised that simultaneous blockade of PD-1:PD-L1/PD-L2 with
v516 | Immunotherapy of Cancer
Pembrolizumab in advanced rare cancers
A. Naing1, F. Meric-Bernstam1, D. Karp1, J.A. Rodon1, S.A. Piha-Paul1, V. Subbiah1, D.S. Hong1, S. Pant1, S. Fu1, F. Janku1, T.A. Yap1, A.M. Tsimberidou1, E.E. Ileana Dumbrava1, R.R. Colen2, K.R. Hess3, M.T. Campbell4, S-M. Tu4, C. Jimenez5, M.A. Habra5, G.R. Varadhachary6 1 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 3Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 4Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 5Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 6Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: Patients with rare cancers account for 25% of cancer-related deaths but have limited treatment options. As immunotherapy has potential applicability across cancer types, we conducted an open-label phase II trial of pembrolizumab in patients with advanced rare cancers.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz253.092/5577612 by guest on 24 October 2019
A phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumours or lymphomas
Annals of Oncology