DNA Damage Repair Pathway Inhibitors: PARP
First-line treatment with/without extended (maintenance) treatment
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
Overall Survival (months)
The length of time where half the patients in the study are still alive
Maintenance after first-line therapy: Treatment to prevent relapse after complete or partial response to therapy
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
Overall Survival (months)
The length of time where half the patients in the study are still alive
Maintenance after therapy for recurrence: Treatment to control disease after complete or partial response to therapy
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
Overall Survival (months)
The length of time where half the patients in the study are still alive
Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after last platinum-based treatment
Objective Response Rate (%)
Percentage of patients whose tumors shrink or go away after treatment
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment
Objective Response Rate (%)
Percentage of patients whose tumors shrink or go away after treatment
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
Treatment given for recurrence occurring at any time after last platinum-based treatment
Objective Response Rate (%)
Percentage of patients whose tumors shrink or go away after treatment
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
DNA Damage Repair Pathway Inhibitors: ATR
Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment
Objective Response Rate (%)
Percentage of patients whose tumors shrink or go away after treatment
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
DNA Damage Repair Pathway Inhibitors: PARP
First-line treatment with/without extended (maintenance) treatment
For more detailed information, please click on the clinical trial ID number.
| Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|
| Drugs in Clinical Development | ||||
| NCT02470585; VELIA | III | Carboplatin, Paclitaxel, Veliparib | A Phase 3 Placebo-Controlled Study of Carboplatin/Paclitaxel With or Without Concurrent and Continuation Maintenance Veliparib (PARP Inhibitor) in Subjects With Previously Untreated Stages III or IV High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | Veliparib added to chemotherapy and continued as maintenance significantly extends PFS in all newly diagnosed patients, but shows most benefit in BRCA MUT patients CarboPt+Pac+Vel w/Vel maint vs CarboPt+Pac+Vel vs CarboPt+Pac: All patients: pub 2019 |
| NCT03326193; OVARIO | II | Bevacizumab, Carboplatin, Niraparib, Paclitaxel | Phase 2, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Niraparib Combined With Bevacizumab as Maintenance Treatment in Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Following Front-line Platinum-based Chemotherapy With Bevacizumab | Niraparib + bevacizumab maintenance treatment does not appear to cause cumulative toxicities and shows promising PFS PFS (6 months): 90% pub 2022 |
| NCT00989651; GOG-9923 | I | Carboplatin, Cisplatin, Paclitaxel, Veliparib, Bevacizumab | A Phase I Study of Intravenous Carboplatin/Paclitaxel or Intravenous and Intraperitoneal Paclitaxel/Cisplatin in Combination With Continuous or Intermittent /CTEP-Supplied Agent ABT-888 (NSC #737664) and CTEP-Supplied Agent Bevacizumab (NSC #704865) in Newly Diagnosed Patients With Previously Untreated Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer | Patients receiving IP cisplatin + IV/IP paclitaxel show promising PFS and OS when compared to patients receiving IV carboplatin+paclitaxel, however differences may be reflective of selection bias toward patients enrolled on the IP chemotherapy arm IV vs weekly IV vs IP (all w/ Vel cont): PFS: 24.5 vs 23.5 vs 43.2 months pub 2020, abs Mar 2020 |
Maintenance after first-line therapy: Treatment to prevent relapse after complete or partial response to therapy
For more detailed information, please click on the clinical trial ID number.
| Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|
| Standard of Care Targeted Drugs | ||||
| NCT01844986; SOLO-1 | III | Olaparib Prescribing Information | A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer Following First Line Platinum Based Chemotherapy (SOLO-1) | Considerably improved PFS for BRCA MUT patients with olaparib maintenance treatment; the benefit derived from 2 years of maintenance olaparib is sustained beyond the end of treatment Ola maint vs Placebo: PFS: 56.0 vs 13.8 months* pub 2018, abs Sep 2020, abs Mar 2021, pub 2021 |
| NCT02477644; PAOLA-1 | III | Carboplatin, Paclitaxel, Olaparib, Bevacizumab Prescribing Information | Randomized, Double-Blind, Phase III Trial Olaparib vs. Placebo Patients With Advanced FIGO Stage IIIB-IV High Grade Serious or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer Treated Standard First-Line Treatment | Dual maintenance therapy with olaparib and bevacizumab significantly improves PFS and PFS2 compared with bevacizumab maintenance alone for BRCA MUT and HRD+ patients Ola vs Placebo: All patients: pub 2019, abs Sep 2020, pub 2022 |
| NCT02655016; PRIMA | III | Niraparib Prescribing Information | A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy | Considerably improved PFS for all patients that received niraparib maintenance treatment Nir maint vs Placebo: All patients: pub 2019, pub 2022 |
| NCT03709316; PRIME | III | Niraparib Prescribing Information | A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase III Clinical Trial Evaluating the Efficacy and Safety of ZL-2306 (Niraparib) for Maintenance Treatment in Patients With Advanced Ovarian Cancer, Fallopian Tube Carcinoma or Primary Peritoneal Cancer (Collectively Referred to as Ovarian Cancer) Who Have Achieved Effective Response After First-line Platinum-containing Chemotherapy | Niraparib with individually starting dose (ISD regimen) significantly improves PFS compared with placebo and is associated with a better safety profile PFS: 24.8 vs 8.3 months* abs Mar 2022 |
| Drugs in Clinical Development | ||||
| NCT03522246; ATHENA-MONO/GOG-3020 | III | Rucaparib | 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) | Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD Ruc maint vs Placebo: All patients: HRD+ (incl. BRCA MUT): BRCA MUT: BRCA WT/LOH high: BRCA WT/LOH low: pub 2022 |
Maintenance after therapy for recurrence: Treatment to control disease after complete or partial response to therapy
For more detailed information, please click on the clinical trial ID number.
| Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|
| Standard of Care Targeted Drugs | ||||
| NCT01874353; SOLO-2 | III | Olaparib Prescribing Information | Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based Chemotherapy (SOLO-2) | Improved PFS and OS with olaparib maintenance treatment in gBRCA MUT patients Ola vs Placebo: PFS: 19.1 vs 5.5 months* pub 2017, pub 2021 |
| NCT01847274; NOVA | III | Niraparib Prescribing Information | A Phase 3 Randomized Double-blind Trial of Maintenance With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer (NOVA) | Improved PFS for all patients with niraparib maintenance with greatest activity in BRCA MUT patients; the benefit of niraparib maintenance therapy extends beyond first progression Nir vs Placebo: non-gBRCA MUT: pub 2016, pub 2019, abs Mar 2021 |
| NCT01968213; ARIEL3 | III | Rucaparib Prescribing Information | Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous and Endometrioid Ovarian Cancer (ARIEL3) | Improved PFS for all patients with rucaparib maintenance irrespective of number of prior therapies or length of PFS interval, but most active in BRCA MUT Ruc vs Placebo: All: pub 2017, pub 2020, abs Jun 2021 and poster, pub 2021 |
| NCT00753545; Study 19 | II | Olaparib Prescribing Information | Phase II Randomised, Double Blind, Multicentre Study to Assess the Efficacy of AZD2281 in the Treatment of Patients With Platinum Sensitive Relapsed Serous Ovarian Cancer Following Treatment With Two or More Platinum Containing Regimens (Study 19) | Improved PFS and OS with olaparib maintenance Ola vs Placebo: All: pub 2012; 2014; 2016 |
| NCT03402841; OPINION | IIIb | Olaparib Prescribing Information | A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non-Germline BRCA Mutated Ovarian Cancer Patients Who Are in Complete or Partial Response Following Platinum Based Chemotherapy | Maintenance olaparib demonstrates activity in non-gBRCA MUT ovarian cancer patients with no new safety signals non-gBRCA MUT: PFS: 9.2 months pub 2022 |
| NCT02476968; ORZORA | IV | Olaparib | An Open Label, Single Arm, Multicentre Study to Assess the Clinical Effectiveness and Safety of Lynparza (Olaparib) Capsules Maintenance Monotherapy in Platinum Sensitive Relapsed Somatic or Germline BRCA Mutated Ovarian Cancer Patients Who Are in Complete or Partial Response Following Platinum Based Chemotherapy (ORZORA). | PFS in patients with platinum sensitive ovarian cancer who received maintenance olaparib is similar irrespective of somatic or germline BRCA status and activity of maintenance olaparib is also seen in patients with a non-BRCA HRR gene mutations gBRCA MUT vs sBRCA MUT vs HRRm: abs Mar 2021 |
| Drugs in Clinical Development | ||||
| NCT03106987; OReO/ENGOT Ov-38 | III | Olaparib | A Phase IIIb, Randomised, Double-blind, Placebo-controlled, Multicentre Study of Olaparib Maintenance Retreatment in Patients With Epithelial Ovarian Cancer Previously Treated With a PARPi and Responding to Repeat Platinum Chemotherapy | Rechallenge with maintenance olaparib following response to Pt-based therapy provides a significant improvement in PFS vs placebo, irrespective of BRCA status Ola vs Placebo: non-BRCA MUT: abs Sept 2021 |
Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after last platinum-based treatment
For more detailed information, please click on the clinical trial ID number.
| Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|
| Standard of Care Targeted Drugs | ||||
| NCT01078662; Study 42 | II | Olaparib Prescribing Information | A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation (Study 42) | Olaparib shows promising responses in heavily pretreated Pt-S gBRCA MUT patients ORR: 46% pub 2016 |
| NCT02354586; QUADRA | II | Niraparib Prescribing Information | A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (QUADRA) | Niraparib shows promising activity in late-line treatment setting BRCA MUT: HRD+ (excl. BRCA MUT): pub 2019 |
| Rucaparib FDA Approval Data | II | Rucaparib Prescribing Information | Treatment of BRCA-mutated Ovarian Cancer After 2 or More Chemotherapies | Rucaparib shows promising responses in BRCA MUT patients ORR: 66% pub 2018 |
| Drugs in NCCN Guidelines | ||||
| NCT02354131; AVANOVA | II | Niraparib, Bevacizumab | Part 1: AVANOVA1 - A Phase I Study to Evaluate the Safety and Tolerability of Bevacizumab-niraparib Combination Therapy and Determine the Recommended Phase 2 Dose (RP2D) in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Part 2: AVANOVA2 - A Two-arm, Open-label, Phase II Randomized Study to Evaluate the Efficacy of Niraparib Versus Niraparib-bevacizumab Combination in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer. | Promising improvement of activity with niraparib+bevacizumab compared to niraparib alone Nir+Bev vs Nir: ORR: 62 vs 30%* pub 2019, abs May 2020 and poster |
| Drugs in Clinical Development | ||||
| NCT02282020; SOLO-3 | III | Gemcitabine, Liposomal doxorubicin, Olaparib, Paclitaxel, Topotecan | A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physician's Choice Single Agent Chemotherapy in the Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients Carrying Germline BRCA1/2 Mutations. | Improved ORR and PFS for gBRCA MUT patients treated with olaparib vs nonplatinum chemotherapy, with similar OS Ola vs TPC: ORR: 72 vs 51%* pub 2020, abs Mar 2022 |
| NCT02446600; NRG-GY004 | III | Carboplatin, Cediranib, Gemcitabine, Liposomal doxorubicin, Olaparib, Paclitaxel | A Phase III Study Comparing Single-Agent Olaparib or the Combination of Cediranib and Olaparib to Standard Platinum-Based Chemotherapy in Women With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | Cediranib+olaparib has similar activity to standard of care in relapsed platinum sensitive ovarian cancer but does not improve PFS; in gBRCA MUT patients cediranib+olaparib and olaparib alone shows substantial activity Ola+Ced vs Ola vs Treatment of Physician's Choice (TPC): ORR: 69.4 vs 52.4 vs 71.3% pub 2022 |
| NCT01116648 | II | Cediranib, Olaparib | Phase I/II Study of Cediranib and Olaparib in Combination for Treatment of Recurrent Papillary-Serous Ovarian, Fallopian Tube, or Peritoneal Cancer or for Treatment of Recurrent Triple-Negative Breast Cancer | Improved ORR, PFS and OS for olaparib+cediranib combination in patients with gBRCA WT or unknown BRCA status Ola+Ced vs Ola: gBRCA WT or UNK: gBRCA MUT: pub 2014; 2019 |
| NCT01540565 | II | Veliparib | A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline BRCA1 or BRCA2 Mutation | Veliparib shows encouraging activity in gBRCA MUT ovarian cancer ORR: 35% Pt-S: ORR: 35%; PFS: 11.0 months pub 2015 |
| NCT01891344; ARIEL2 | II | Rucaparib | A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2) | Improved ORR and PFS with rucaparib treatment in BRCA MUT patients BRCA MUT vs BRCA WT LOH high vs BRCA WT LOH low: ORR: 80 vs 29 vs 10%* pub 2017, abs May 2020 and poster |
| NCT02345265 | II | Cediranib, Olaparib | A Phase 2 Study of Olaparib and Cediranib for the Treatment of Recurrent Ovarian Cancer | Olaparib+cediranib is effective independent of gBRCA status ORR: 74.3% abs Jun 2018 |
| NCT02983799; LIGHT | II | Olaparib | Non-Randomized, Open-Label Phase II Study to Assess Olaparib Tablets as a Treatment for Subjects With Different HRD Tumor Status and With Platinum-Sensitive, Relapsed, High-Grade Serous or High-Grade Endometrioid Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That Have Received at Least 1 Prior Line of Chemotherapy | Olaparib treatment has activity across all cohorts with similar efficacy in the gBRCA MUT and sBRCA MUT cohorts. For non-BRCA MUT patients, longer median PFS and higher ORR are observed in the HRD+ cohort gBRCA MUT: abs May 2020 and poster |
| NCT02734004; MEDIOLA | I/II | Durvalumab, Olaparib, Bevacizumab | A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Olaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors | Promising activity of olaparib+durvalumab in gBRCA MUT ovarian cancer patients; olaparib+durvalumab+bevacizumab shows promising activity in non-gBRCA MUT patients regardless of LOH score and mutation status of common DDR genes Ola+Dur, gBRCA MUT: Ola+Dur, non-gBRCA MUT: Ola+Dur+Bev, non-gBRCA MUT: abs Oct 2019, abs Sep 2020, pub 2020 |
| NCT03333915 | I/II | Pamiparib | An Open Label, Multi-Center Phase I/II Study to Evaluate Efficacy and Safety of BGB-290 in Chinese Subjects With Advanced Ovarian Cancer, Fallopian Cancer, and Primary Peritoneal Cancer or Advanced Triple Negative Breast Cancer | Pamiparib showes antitumor activity with durable responses in patients with gBRCA MUT platinum sensitive or platinum resistant ovarian cancer and has a manageable safety profile Pt-S: pub 2021 |
| NCT02660034 | I/Ib | Pamiparib, Tislelizumab | 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 | Pamiparib+tislelizumab is well tolerated and associated with antitumor responses in both BRCA WT and BRCA MUT ovarian cancer 16 evaluable Pt-S: pub 2019 |
Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment
For more detailed information, please click on the clinical trial ID number.
| Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|
| Standard of Care Targeted Drugs | ||||
| NCT01078662; Study 42 | II | Olaparib Prescribing Information | A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation (Study 42) | Olaparib shows promising responses in heavily pretreated Pt-R gBRCA MUT patients ORR: 30% pub 2016 |
| NCT02354586; QUADRA | II | Niraparib Prescribing Information | A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (QUADRA) | Niraparib shows promising activity in platinum resistant patients in late-line treatment setting BRCA MUT: pub 2019 |
| Rucaparib FDA Approval Data | II | Rucaparib Prescribing Information | Treatment of BRCA-mutated Ovarian Cancer After 2 or More Chemotherapies | Rucaparib shows promising responses in BRCA MUT patients ORR: 25% pub 2018 |
| Drugs in Clinical Development | ||||
| NCT01891344; ARIEL2 | II | Rucaparib | A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2) | In platinum resistant patients rucaparib is most effective in patients that have BRCA1/2 mutations BRCA MUT vs BRCA WT LOH high vs BRCA WT LOH low: ORR: 23.4 vs 4.1 vs 5.4% pub 2021 |
| NCT03699449 | II | Cediranib, Olaparib | An uMbrella Study of BIomarker-driven Targeted Therapy In Patients With Platinum-resistant Recurrent OvariaN Cancer(AMBITION) | Olaparib+cediranib shows promising activity in BRCA MUT patients ORR: 50% abs Jun 2021 and poster, pub 2022 |
| NCT03699449 | II | Durvalumab, Olaparib | An uMbrella Study of BIomarker-driven Targeted Therapy In Patients With Platinum-resistant Recurrent OvariaN Cancer(AMBITION) | Olaparib+durvalumab shows promising activity in BRCA MUT patients ORR: 35.7% abs Jun 2021 and poster, pub 2022 |
| NCT01540565 | II | Veliparib | A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline BRCA1 or BRCA2 Mutation | Veliparib shows encouraging activity in gBRCA MUT ovarian cancer ORR: 20% Pt-S: ORR: 35%; PFS: 11.0 months pub 2015 |
| NCT02345265 | II | Cediranib, Olaparib | A Phase 2 Study of Olaparib and Cediranib for the Treatment of Recurrent Ovarian Cancer | Olaparib+cediranib combination shows activity in Pt-R patients ORR: 20% gBRCA WT: gBRCA MUT: abs Jun 2018 |
| NCT02354586; QUADRA | II | Niraparib | A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (QUADRA) | Niraparib shows some activity in platinum resistant patients in late-line treatment setting HRD+ (incl. BRCA MUT): HRD+ (excl. BRCA MUT): pub 2019 |
| NCT02889900; CONCERTO | II | Cediranib, Olaparib | A Single Arm, Open-label, Phase IIb Study to Assess the Efficacy and Safety of the Combination of Cediranib and Olaparib Tablets in Women With Recurrent Platinum Resistant Epithelial Ovarian Cancer, Including Fallopian Tube and/or Primary Peritoneal Cancer Who do Not Carry a Deleterious or Suspected Deleterious Germline BRCA Mutation | Olaparib+cediranib has manageable toxicity and shows evidence of anti-tumor activity in heavily pretreated platinum resistant non-gBRCA MUT patients ORR: 15.6% abs May 2020 and poster
|
| NCT03314740; BAROCCO | II | Cediranib, Olaparib | The BAROCCO Study (Best Approach in Recurrent-Ovarian-Cancer-with Cediranib-Olaparib): an Italian Multicenter Randomized Phase II Study of Weekly Paclitaxel vs. Cediranib-Olaparib With Continuous Schedule vs. Cediranib-Olaparib With Intermittent Schedule in Patients With Platinum Resistant High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. | The combination of olaparib and cediranib is not superior to chemotherapy in terms of PFS in heavily pretreated platinum resistant ovarian cancer patients. However, this oral doublet, is active and may offer a non-chemotherapy option in this difficult to treat population Ced+Ola (continuous) vs Ced+Ola (intermittent) vs Pac: PFS: 5.6 vs 3.8 vs 3.1 months gBRCA WT: pub 2022 |
| NCT03574779; OPAL | II | Dostarlimab, Niraparib, Bevacizumab | Phase 2 Multicohort Study to Evaluate the Safety and Efficacy of Novel Treatment Combinations in Patients With Recurrent Ovarian Cancer | Triplet therapy with niraparib, dostarlimab, and bevacizumab is tolerable and demonstrates clinical activity in patients with BRCA WT platinum resistant ovarian cancer without HRR gene mutations ORR: 17.9% w/ prior Bev: ORR: 6% abs Mar 2021 |
| NCT02657889; TOPACIO | I/II | Pembrolizumab, Niraparib | 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 (TOPACIO) | Promising activity of niraparib+pembrolizumab in platinum resistant patients independent of BRCA status, HRD status and PD-L1 expression ORR: 21% pub 2019 |
| NCT03333915 | I/II | Pamiparib | An Open Label, Multi-Center Phase I/II Study to Evaluate Efficacy and Safety of BGB-290 in Chinese Subjects With Advanced Ovarian Cancer, Fallopian Cancer, and Primary Peritoneal Cancer or Advanced Triple Negative Breast Cancer | Pamiparib showes antitumor activity with durable responses in patients with gBRCA MUT platinum sensitive or platinum resistant ovarian cancer and has a manageable safety profile Pt-R: pub 2021 |
| NCT02660034 | I/Ib | Pamiparib, Tislelizumab | 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 | Pamiparib+tislelizumab is well tolerated and associated with antitumor responses in both BRCA WT and BRCA MUT ovarian cancer 18 evaluable Pt-R: pub 2019 |
| NCT01623349 | I | Alpelisib, Olaparib | Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer | Encouraging activity of alpelisib+olaparib combination, also in BRCA WT patients ORR: 34.6% gBRCA WT: ORR: 31.3% pub 2019 |
Treatment given for recurrence occurring at any time after last platinum-based treatment
For more detailed information, please click on the clinical trial ID number.
| Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|
| Drugs in Clinical Development | ||||
| NCT02855944; ARIEL4 | III | Carboplatin, Cisplatin, Gemcitabine, Paclitaxel, Rucaparib | ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | Recurrent BRCA MUT patients, including those who are platinum sensitive or platinum resistant, receive benefit with rucaparib treatment when compared to chemotherapy; the presence of a BRCA reversion mutation predicts for primary resistance to rucaparib Ruc vs TPC: ORR: 40.3 vs 32.3% pub 2022 |
| NCT01891344; ARIEL2 | II | Rucaparib | A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2) | Administration of rucaparib as active treatment should be considered in earlier lines of therapy before the emergence of platinum resistance. RAD51C/D mutation and high-level BRCA1 promotor methylation predict response to rucaparib, similar to BRCA1/2 mutations, but LOH high is only predictive of response in platinum-sensitive patients BRCA MUT vs BRCA WT LOH high vs BRCA WT LOH low: ORR: 80 vs 29 vs 10%* pub 2021 |
| NCT03579316 | II | Adavosertib, Olaparib | EFFORT: Efficacy of AZD1775 in Parp Resistance; A Randomized 2-Arm, Non-Comparative Phase 2 Study of AZD1775 Alone or AZD1775 and Olaparib in Women With Ovarian Cancer Who Have Progressed During PARP Inhibition | Adavosertib alone and in combination with olaparib demonstrates efficacy in patients with PARPi-resistant ovarian cancer irrespective of BRCA status Ada+Ola vs Ada: ORR: 29 vs 23%; DoR: 6.4 vs 5.5 months: DCR (4 months): 89 vs 63%; PFS: 6.8 vs 5.5 months BRCA MUT: abs Jun 2021 and presentation |
| NCT02511795 | Ib | Adavosertib, Olaparib | A Phase Ib Study of AZD1775 and Olaparib in Patients With Refractory Solid Tumours | Olaparib+adavosertib shows anti-tumor activity, particularly at the twice daily (BID) schedule ORR: 15% abs Apr 2019 and poster |
| NCT02484404 | I/II | Durvalumab, Cediranib, Olaparib | Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab (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 | Promising response rates for olaparib, cediranib and durvalumab combinations in ovarian cancer Ola+Dur: Ola+Ced+Dur: 7 evaluable pub 2017; abs Oct 2018, pub 2019 |
| NCT01286987 | I | Talazoparib | A Phase 1, First In Human, Single-arm, Open-label Study Of Once A Day, Orally Administered Talazoparib (Bmn 673) In Patients With Advanced Or Recurrent Solid Tumors | Talazoparib shows promising activity in gBRCA MUT ovarian cancer ORR: 41.7% pub 2017 |
| NCT02338622 | I | Capivasertib, Olaparib | A Phase I Multi-centre Trial of the Combination of Olaparib (PARP Inhibitor) and AZD5363 (AKT Inhibitor) in Patients With Advanced Solid Tumours | Capivasertib+olaparib is safe and tolerable and anti-tumor activity is observed in patients harboring tumors with BRCA MUT and BRCA WT cancers with or without somatic DDR and/or PI3K-AKT pathway alterations ORR: 24% pub 2020 |
| NCT01650376 | 1b | Carboplatin, Paclitaxel, Olaparib | Phase Ib With Expansion of Patients at the MTD Study of Olaparib Plus Weekly (Metronomic) Carboplatin and Paclitaxel in Relapsed Ovarian Cancer Patients | Olaparib can be safely administered with metronomic carboplatin and paclitaxel in recurrent ovarian cancer, but BRCA MUT patients experience most benefit ORR: 54% BRCA MUT vs BRCA WT: pub 2019 |
DNA Damage Repair Pathway Inhibitors: ATR
Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment
For more detailed information, please click on the clinical trial ID number.
| Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|
| Drugs in Clinical Development | ||||
| NCT02595892 | II | Berzosertib, Gemcitabine | Phase 2 Study of M6620 (VX-970) in Combination With Gemcitabine Versus Gemcitabine Alone in Subjects With Platinum-Resistant Recurrent Ovarian or Primary Peritoneal Fallopian Tube Cancer | Addition of berzosertib to gemcitabine increases PFS without additional toxicity, the benefit was observed mainly in patients with platinum-free interval less than 3 months Ber+Gem vs Gem: PFS: 5.7 vs 3.7 months* pub 2020, pub 2021 |