The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer
Abstract
:1. Introduction
2. Challenges to PD-1 Therapy
2.1. Unique Tumor Microenvironment
2.2. Elevated Levels of Highly Activated T Regulatory Cells
2.3. Patient Selection Barriers
3. PD-1 Based Combinatorial Approaches
3.1. PD-1 and Chemotherapy
3.1.1. Preclinical Studies
3.1.2. Clinical Studies
3.2. PD-1 and Anti-Angiogenic Therapy
3.2.1. Preclinical Studies
3.2.2. Clinical Studies
3.3. PD-1 and PARP Therapy
3.3.1. Preclinical Studies
3.3.2. Clinical Studies
3.4. PD-1 and Additional Immune Receptor Targeting
3.4.1. Preclinical Studies
3.4.2. Clinical Studies
3.5. PD-1 and Novel Immunotherapies
3.5.1. Preclinical Studies
3.5.2. Clinical Studies
3.6. PD-1 and Other Agents
3.6.1. Preclinical Studies
3.6.2. Clinical Studies
4. Discussion
5. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Study Title | Trial Identifier | Study Arm(s) | Primary Endpoint(s) | Results |
---|---|---|---|---|
A Phase 1b to Assess the Safety and Tolerability of Carboplatin-Cyclophosphamide Combined with Atezolizumab, an Antibody That Targets Programmed Death Ligand 1 (PD-L1), in Patients with Advanced Breast Cancer and Gynecologic Cancer | NCT02914470 | Single Arm | Toxicity; AEs | N/A |
Matched Paired Pharmacodynamics and Feasibility Study of Durvalumab in Combination with Chemotherapy in Frontline Ovarian Cancer (N-Dur) | NCT02726997 | Single Arm | Pharmacodynamic changes | N/A |
Anti-PD-1 Therapy in Combination with Platinum Chemotherapy for Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer | NCT03029598 | Single Arm | PFS | N/A |
A Phase II Study of Pembrolizumab With Cisplatin and Gemcitabine Treatment in Patients with Recurrent Platinum-Resistant Ovarian Cancer | NCT02608684 | Single Arm | ORR by RECIST | CR: 5.6% PR: 55.6% SD: 27.8% PD: 11.1% |
Phase II Open Label Nonrandomized Trial of the Anti PD-1 Therapy Pembrolizumab with First Line Platinum-Based Chemotherapy Followed by 12 Months Pembrolizumab Monotherapy for Patients with Stage III/IV Epithelial Ovarian Cancer | NCT02766582 | Single Arm | PFS | N/A |
Matched Paired Pharmacodynamics and Feasibility Study of Pembrolizumab in Combination with Chemotherapy in Frontline Ovarian Cancer | NCT02520154 | Single Arm | PFS | N/A |
Phase II Single Arm Study of Combination Pembrolizumab, Paclitaxel, and Carboplatin in Patients with Advanced Stage Ovarian, Fallopian Tube, or Peritoneal Carcinoma Receiving Neoadjuvant Chemotherapy | NCT02834975 | Single Arm | pORR | N/A |
A Phase II Study of Pembrolizumab Combined with Pegylated Liposomal Doxorubicin (PLD) for Recurrent Platinum Resistant Ovarian, Fallopian Tube or Peritoneal Cancer | NCT02865811 | Single Arm | CBR | ORR: 11.5% [72] |
A Randomized, Open-label, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Avelumab (MSB0010718C) in Combination with and/or Following Chemotherapy in Patients with Previously Untreated Epithelial Ovarian Cancer JAVELIN OVARIAN 100 | NCT02718417 | Arm 1: Chemotherapy Arm 2: Chemotherapy + avelumab maintenance Arm 3: Chemotherapy + avelumab + avelumab maintenance | PFS | Arm 1: N/A Arm 2: PFS: 16.8 months Arm 3: PFS: 18.1 months Study Terminated |
A Phase 3, Multicenter, Randomized, Open-label Study of Avelumab (MSB0010718C) Alone or in Combination with Pegylated Liposomal Doxorubicin Alone in Patients with Platinum-Resistant/Refractory Ovarian Cancer | NCT02580058 | Arm 1: Avelumab Arm 2: Avelumab + PLD Arm 3: PLD | OS; PFS | Arm 1: OS: 11.8 months PFS: 1.9 months Arm 2: OS: 15.7 months PFS: 3.7 months Arm 3: OS: 13.1 months PFS: 3.5 months |
Study Title | Trial Identifier | Study Arm(s) | Primary Endpoint(s) | Results |
---|---|---|---|---|
Phase Ib Trial of Pembrolizumab and Nintedanib | NCT02856425 | Single Arm | MTD of Nintedanib | N/A |
A Phase II Study of the Anti-PDL1 Antibody Atezolizumab, Bevacizumab and Acetylsalicylic Acid to Investigate Safety and Efficacy of This Combination in Recurrent Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Adenocarcinoma | NCT02659384 | Arm 1: Bevacizumab Arm 2: Atezolizumab + Bevacizumab Arm 3: Atezolizumab + Bevacizumab + Acetylsalicylic Acid | PFS | N/A |
A Phase II Study with a Safety Lead-in of Nivolumab in Combination with Bevacizumab or in Combination with Bevacizumab and Rucaparib for the Treatment of Relapsed Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer | NCT02873962 | Arm 1: Nivolumab + Bevacizumab Arm 2: Nivolumab + Bevacizumab + Rucaparib | ORR by RECIST | ORR: 28.9% (40% platinum-sensitive 16.7% platinum- resistant) [79] |
A Randomized, Phase II/III Study of Pegylated Liposomal Doxorubicin and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin/Bevacizumab and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin/Bevacizumab in Platinum-Resistant Ovarian Cancer | NCT02839707 | Arm 1: PLD + Atezolizumab Arm 2: PLD + Bevacizumab + Atezolizumab Arm 3: PLD + Bevacizumab | DLT; PFS; OS | N/A |
Atezolizumab in Combination with Bevacizumab and Chemotherapy versus Bevacizumab and Chemotherapy in Recurrent Ovarian Cancer—ARandomized Phase III Trial | NCT03353831 | Arm 1: Chemotherapy + Bevacizumab Arm 2: Chemotherapy + Bevacizumab + Atezolizumab | OS; PFS | N/A |
A Phase III, Multicenter, Randomized, Study of Atezolizumab versus Placebo Administered in Combination with Paclitaxel, Carboplatin, and Bevacizumab to Patients with Newly Diagnosed Stage III or Stage IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | NCT03038100 | Arm 1: Atezolizumab + Paclitaxel, Carboplatin and Bevacizumab Arm 2: Paclitaxel, Carboplatin and Bevacizumab | PFS, OS | N/A |
A Randomized, Double-Blinded, Phase III Study of Atezolizumab versus Placebo in Patients with Late Relapse of Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Treated by Platinum-Based Chemotherapy and Bevacizumab | NCT02891824 | Arm 1: Bevacizumab + Chemotherapy Arm 2: Atezolizumab + Bevacizumab + Chemotherapy | PFS | N/A |
Study Title | Trial Identifier | Study Arm(s) | Primary Endpoint(s) | Results |
---|---|---|---|---|
A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination with the PARP Inhibitor BGB-290 in Subjects with Advanced Solid Tumors | NCT02660034 | Single Arm | Phase 1: AEs; DLT; MTD Phase 1b: ORR, PFS DOR, DCR, CBR, OS | PR: 7(5 EOC)/38 patients CR:1(EOC)/38 patients [89] |
A Phase I/II Evaluation of Olaparib in Combination with Durvalumab (Medi4736) and Tremelimumab in the Treatment of Recurrent Platinum-Sensitive or Resistant or Refractory Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Patients Who Carry a BRCA1 or BRCA2 Mutation | NCT02953457 | Single Arm | DLT, PFS | N/A |
Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody MEDI4736 in Combination with Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Cancers | NCT02484404 | Sequential Assignment | Phase I: RP2D Phase II: ORR | DCR: 53% [91] |
Phase 1/2 Clinical Study of Niraparib in Combination with Pembrolizumab (MK-3475) in Patients with Advanced or Metastatic Triple-Negative Breast Cancer and in Patients with Recurrent Ovarian Cancer | NCT02657889 | Single Arm | Phase I: DLT, AEs Phase II: ORR | ORR:25%, [87] |
A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination with Olaparib (PARP Inhibitor) in Patients with Advanced Solid Tumors | NCT02734004 | Single Arm | DCR, Safety and tolerability, ORR | DCR:81% ORR:63% [90] |
A Phase 2, Open-label Study to Evaluate Rucaparib in Combination with Nivolumab in Patients with Selected Solid Tumors (ARIES) | NCT03824704 | Single Arm | ORR | N/A |
Phase 2 Multicohort Study to Evaluate the Safety and Efficacy of Novel Treatment Combinations in Patients with Recurrent Ovarian Cancer | NCT03574779 | Single Arm | ORR | N/A |
ATHENA (A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy) | NCT03522246 | Arm 1: Rucaparib + nivolumab Arm 2: Rucaparib Arm 3: Nivolumab Arm 4: Placebo | PFS | N/A |
ENGOT-0V44 The FIRST (First-Line Ovarian Cancer Treatment with Niraparib Plus TSR-042) Study: A Randomized, Double-Blind, Phase 3 Comparison of Platinum-Based Therapy with TSR-042 and Niraparib Versus Standard of Care Platinum-Based Therapy as First-Line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer | NCT03602859 | Arm 1: Chemotherapy + Bevacizumab Arm 2: Chemotherapy + Niraparib Arm 3: Chemotherapy + TSR-042 | PFS | N/A |
A Randomized Phase 3, Double-Blind Study of Chemotherapy with or without Pembrolizumab Followed by Maintenance with Olaparib or Placebo for the First-Line Treatment of BRCA Non-Mutated Advanced Epithelial Ovarian Cancer (EOC) (KEYLYNK-001/ENGOT-ov43) | NCT03740165 | Arm 1: Pembrolizumab + Olaparib Arm 2: Pembrolizumab Arm 3: Placebo | PFS; OS | N/A |
A Randomized, Open-Label Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Avelumab in Combination with Chemotherapy Followed by Maintenance Therapy of Avelumab in Combination with the Poly (Adenosine Diphosphate [ADP]-Ribose) POLYMERASE (PARP) Inhibitor Talazoparib in Patients with Previously Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP100) | NCT03642132 | Arm 1: Chemotherapy + Avelumab + Talazoparib Arm 2: Chemotherapy + Talazoparib Arm 3: Chemotherapy + Bevacizumab | PFS | Study Discontinued |
A Phase III Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Durvalumab in Combination with Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O). | NCT03737643 | Arm 1: Chemotherapy + Bevacizumab + maintenance Bevacizumab, Arm 2: Chemotherapy + Bevacizumab + Durvalumab + maintenance Bevacizumab + Durvalumab Arm 3: Chemotherapy + Bevacizumab +Durvalumab + maintenance Bevacizumab + Durvalumab + Olaparib. tBRCAm cohort: Chemotherapy + Bevacizumab + Durvalumab + maintenance Bevacizumab + Durvalumab + Olaparib. | PFS | N/A |
Study Title | Trial Identifier | Study Arm(s) | Primary Endpoint(s) | Results |
---|---|---|---|---|
A Phase 1 Study to Evaluate the Safety and Tolerability of Anti-PD-L1, MEDI4736, in Combination with Tremelimumab in Subjects with Advanced Solid Tumors | NCT01975831 | Single Arm | AEs | N/A |
A Phase 1, Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Orally Administered CA-170 in Patients with Advanced Tumors and Lymphomas | NCT02812875 | Single Arm | DLT; MTD; RP2D | N/A |
A Phase I Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination with Tremelimumab (Anti-CTLA-4 Antibody) in Subjects with Advanced Solid Tumors | NCT02261220 | Single Arm | AEs, SAEs, DLT, ORR | N/A |
A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination with Pembrolizumab and in Combination with MGA012 in Patients with Melanoma, Squamous Cell Cancer of the Head and Neck, Non-Small Cell Lung Cancer, Urothelial Cancer, and Other Cancers | NCT02475213 | Sequential Assignment | AEs; SAEs | N/A |
A Phase 1a/1b Study of COM701 as Monotherapy and in Combination with an Anti-PD-1 Antibody in Subjects with Advanced Solid Tumors | NCT03667716 | Arm 1: Monotherapy dose escalation Arm 2: Combination dose escalation Arm 3: Monotherapy expansion Arm 4: Combination dose expansion | AEs; MTD | N/A |
A Phase Ib Study of the Safety and Pharmacology of Atezolizumab (Anti−Pd-L1 Antibody) Administered with Ipilimumab, Interferon-Alpha, or Other Immune-Modulating Therapies in Patients with Locally Advanced or Metastatic Solid Tumors | NCT02174172 | Arm 1: Atezolizumab + Ipilimumab Arm 2: Atezolizumab + Interferon alfa-2 Arm 3: Atezolizumab + Peg- Interferon alfa-2a Arm 4: Atezolizumab + Peg-Interferon alfa-2a+ Bevacizumab Arm 5: Atezolizumab + Obinutuzumab | RP2D; AEs | N/A |
A Phase 1/2, Open-Label Study of Nivolumab Monotherapy or Nivolumab Combined with Ipilimumab in Subjects with Advanced or Metastatic Solid Tumors | NCT01928394 | Arm 1: Nivolumab Arm 2–5: Nivolumab + Ipilimumab at various dosages Arm 6: Nivolumab + Ipilimumab + Cobimetinib | ORR | OC Arm N-I Dose Level 2: ORR: 12.2% AEs: 58.54% OC Arm N-I Dose Level 2b: ORR: 7.0% AEs: 72.09% OC Arm N-I Dose Level 2c: ORR: 9.5% AEs: 69.05% |
Phase II Randomized Trial of Nivolumab with or without Ipilimumab in Patients with Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer | NCT02498600 | Arm 1: Nivolumab Arm 2: Nivolumab + Ipilimumab | ORR | ORR: 12.2% (Arm 1), 31.4% (Arm 2) PFS: 2 mo. (Arm 1), 3.9 mo. (Arm 2) [105] |
A Phase II Clinical Trial Evaluating Ipilimumab and Nivolumab in Combination for the Treatment of Rare Gastrointestinal, Neuro-Endocrine and Gynecological Cancers | NCT02923934 | Single Arm | CBR | N/A |
Modular Phase 2 Study to Link Combination Immune-Therapy to Patients with Advanced Solid and Hematologic Malignancies. Module 9: PDR001 Plus LAG525 for Patients with Advanced Solid and Hematologic Malignancies. | NCT03365791 | Single Arm | CBR; PFS | N/A |
Randomized Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab Administered in Combination versus Sequentially in Recurrent Platinum-Resistant Epithelial Ovarian Cancer | NCT03026062 | Arm 1: Sequential Tremelimumab + Durvalumab Arm 2: Combination Tremelimumab + Durvalumab | irPFS | N/A |
Study Title | Trial Identifier | Study Arm(s) | Primary Endpoint(s) | Results |
---|---|---|---|---|
A Phase I Study of Concomitant WT1 Analog Peptide Vaccine with Montanide and GM-CSF in Combination with Nivolumab in Patients with Recurrent Ovarian Cancer Who Are in Second or Greater Remission | NCT02737787 | Single Arm | DLT | 1-year PFS: 64.0% [115] |
A Phase 1a/1b Study of Cabiralizumab in Combination with Nivolumab in Patients with Selected Advanced Cancers | NCT02526017 | Arm 1: Cabiralizumab Arm 2: Cabiralizumab + Nivolumab | AEs; SAEs; RD; ORR | N/A |
Phase Ib Trial of Pembrolizumab Administered in Combination with or Following Adoptive Cell Therapy—A Multiple Cohort Study; the ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial | NCT03158935 | Arm 1: Cyclophosphamide and fludarabine followed by TILs, IL-2, and Pembrolizumab (Advanced metastatic melanoma) Arm 2: Cyclophosphamide followed by TILs, IL-2, and Pembrolizumab (Advanced ovarian cancer) | SAEs | N/A |
A Prospective Study of Hyperthermia Combined with Autologous Adoptive Cellular Immunotherapy in the Treatment of Abdominal and Pelvic Malignancies or Metastases | NCT03757858 | Arm 1: HT + ACT Arm 2: HT + ACT + Pembrolizumab Arm 3: HT + ACT + CT Arm 4: HT + CT | AEs; ORR | ORR: 30.0% DCR: 66.7% [113] |
T-Cell Therapy in Combination with Checkpoint Inhibitors for Patients with Advanced Ovarian, Fallopian Tube and Primary Peritoneal Cancer | NCT03287674 | Single Arm | AEs | N/A |
A Phase I/II Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-CD27 Antibody (Varlilumab) Administered in Combination with Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors | NCT02335918 | Single Arm | Phase I: AEs Phase II: ORR; OS | PR:3(1 EOC)/36 patients SD: 11/36 patients [116] |
Phase 1/2 Study of Chemoimmunotherapy with Toll-like Receptor 8 Agonist Motolimod (VTX-2337) + Anti-PD-L1 Antibody MEDI4736 in Subjects with Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin is Indicated | NCT02431559 | Arm 1: Durvalumab + PLD + motolimod dose 0a Arm 2: Durvalumab + PLD + motolimod dose 0b Arm 3: Durvalumab + PLD + motolimod dose level 1 Arm 4: Durvalumab + PLD | AEs; PFS | Arm 1: SAEs: 0.0% AEs: 100.0% PFS at 6 months: 33.3% PFS: 5.6 mo. CR: 0.0% PR: 33.3% SD: 33.3% PD: 33.3% Arm 2: SAEs: 50.0% AEs: 100.0% PFS at 6 months: 50.0% PFS: 5.7 mo. CR: 0.0% PR: 25.0% SD: 25.0% PD: 50.0% Arm 3: SAEs: 16.7% AEs: 100.0% PFS at 6 mo.: 33.3% PFS: 4.3 mo. CR: 0.0% PR: 33.3% SD: 16.7% PD: 50.0% Arm 4: SAEs: 57.5% AEs: 100.0% PFS at 6 mo.: 42.9% PFS: 5.5 mo. CR: 5.0% PR: 10.0% SD: 45.0% PD: 40.0% |
Phase 1/2a Study of Double-Immune Suppression Blockade by Combining a CSF1R Inhibitor (PLX3397) with an Anti-PD-1 Antibody (Pembrolizumab) to Treat Advanced Melanoma and Other Solid Tumors | NCT02452424 | Single Arm | AEs | Study Terminated |
A Phase II Trial of TPIV200/huFR-1 (A Multi-Epitope Anti-Folate Receptor Vaccine) Plus Anti-PD-L1 MEDI4736 (Durvalumab) in Patients with Platinum Resistant Ovarian Cancer | NCT02764333 | Single Arm | ORR | Acceptable Combinatorial Safety Profile (114) |
A Randomized, Intra-Patient Crossover, Safety, Biomarker and Anti-Tumor Activity Assessment of the Combination of Atezolizumab and Vigil in Patients with Advanced Gynecological Cancers | NCT03073525 | Arm 1: Vigil + Atezolizumab Arm 2: Vigil and Vigil + Atezolizumab Arm 3: Atezolizumab and Vigil + Atezolizumab Arm 4: Atezolizumab | AEs | N/A |
Pilot Study of Durvalumab (MEDI4736) in Combination with Vigil in Advanced Women’s Cancers | NCT02725489 | Arm 1: 1 × 106 cells Vigil Arm 2: 1 × 107 cells Vigil Arm 3: 1 × 105 cells Vigil | AEs | N/A |
A Phase II Study Using Short-Term Cultured, Autologous Tumor-Infiltrating Lymphocytes Following a Lymphodepleting Regimen in Metastatic Cancers Plus the Administration of Pembrolizumab | NCT01174121 | Arm 1: CD8 + TILs + Aldesleukin + Cyclophosphamide + Fludarabine Arm 2: Unselected TILs + Aldesleukin+ Cyclophosphamide + Fludarabine Arm 3: Unselected TILs + Pembrolizumab + Cyclophosphamide Arm 4: Unselected TILs + Cyclophosphamide + Aldesleukin_ Fludarabine + Pembrolizumab | Response rate | N/A |
Study Title | Trial Identifier | Study Arm(s) | Primary Endpoint(s) | Results |
---|---|---|---|---|
A Phase I Dose Finding Study of Oral LXH254 in Adult Patients with Advanced Solid Tumors Harboring MAPK Pathway Alterations | NCT02607813 | Arm 1: Dose escalation LXH254 Arm 2–4: Dose expansion LXH254 Arm 5: Dose expansion LXH254 + PDR001 Arm 6: Dose escalation LXH254 + PDR001 | AEs; DLT | N/A |
A Phase 1A/B Study to Evaluate the Safety and Tolerability of ETC-1922159 in Advanced Solid Tumors | NCT02521844 | Arm 1: ETC-1922159 + Pembrolizumab Arm 2: ETC-1922159 until progression, then Pembrolizumab added | MTD; RD; AEs | N/A |
A Randomized, Placebo-Controlled, Double-Blind, Multicenter Phase 1b/2 Study of Avelumab with or without Entinostat in Patients with Advanced Epithelial Ovarian Cancer which has Progressed or Recurred after First-Line Platinum-Based Chemotherapy and at Least Two Subsequent Lines of Treatment with a Safety Lead-In | NCT02915523 | Arm 1: Entinostat + Avelumab Arm 2: Avelumab | AEs; DLT; MTD /RP2D | PFS: 1.64 mo. (Arm 1) 1.51 mo. (Arm 2) AEs (any grade): 93% (Arm 1) 78% Arm (2) [128] |
A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination with Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab + Carboplatin in Adults with Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer | NCT02606305 | Arm 1: Dose escalation and dose expansion IMGN853 +Bevacizumab Arm 2: Dose escalation IMGN853 + Carboplatin Arm 3: Dose escalation IMGN853 + PLD Arm 4: Dose escalation and dose expansion IMGN853 + Pembrolizumab Arm 5: Dose expansion IMGN853 + Bevacizumab + Carboplatin | TEAEs; SAEs; DLT; ORR | IMGN853 Combinations safe and tolerable [129] |
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of MK-3475 in Combination with INCB024360 in Subjects with Selected Cancers (ECHO-202/KEYNOTE-037) | NCT02178722 | Single Arm | AEs; ORR | ORR: EOC: 8.1% |
Phase II Trial of Concurrent Anti-PD-L1 and SAbR for Patients with Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer (with Safety Lead-In) | NCT03312114 | Single Arm | ORR | Study Terminated |
A Phase 2 Proof-of-Concept Study of ACP-196 Alone and in Combination with Pembrolizumab in Subjects with Recurrent Ovarian Cancer | NCT02537444 | Arm 1: Acalabrutinib Arm 2: Acalabrutinib + Pembrolizumab | OR | OR: 2.9% (Arm1) 9.1% (Arm 2) SAEs: 21.05% (Arm 1) 41.03% (Arm 2) |
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James, N.E.; Woodman, M.; DiSilvestro, P.A.; Ribeiro, J.R. The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer. Cancers 2020, 12, 2150. https://doi.org/10.3390/cancers12082150
James NE, Woodman M, DiSilvestro PA, Ribeiro JR. The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer. Cancers. 2020; 12(8):2150. https://doi.org/10.3390/cancers12082150
Chicago/Turabian StyleJames, Nicole E., Morgan Woodman, Paul A. DiSilvestro, and Jennifer R. Ribeiro. 2020. "The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer" Cancers 12, no. 8: 2150. https://doi.org/10.3390/cancers12082150