Drug Class: DNA Damage Repair Pathway Inhibitors

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

No Prior Therapies

Maintenance after first-line therapy: Treatment to prevent relapse after complete 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

1 Prior Therapy

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

2 Prior Therapies 3 Prior Therapies Prior Therapies Not Reported

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

1 Prior Therapy 2 Prior Therapies 4 Prior Therapies 5 Prior Therapies Prior Therapies Not Reported

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

2 Prior Therapies 3 Prior Therapies 4 Prior Therapies 5 Prior Therapies Prior Therapies Not Reported

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

Prior Therapies Not Reported

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 extended PFS in all newly diagnosed patients

CarboPt+Pac+Vel w/Vel maint vs CarboPt+Pac+Vel vs CarboPt+Pac:

BRCA MUT:
PFS: 34.7 vs 21.1 vs 22.0 months*
HRD-pos (incl. BRCA MUT):
PFS: 31.9 vs 18.1 vs 20.5 months*
All patients:
PFS: 23.5 vs 15.2 vs 17.3 months*

pub 2019

*Statistically significant result

Maintenance after first-line therapy: Treatment to prevent relapse after complete 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

Ola maint vs Placebo:

PFS: Not Reached vs 14.1 months*

pub 2018

Drugs in Clinical Development
NCT02477644: PAOLA III Bevacizumab, Carboplatin, Olaparib, Paclitaxel 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 compared with bevacizumab maintenance alone

Ola vs Placebo:

All patients:
PFS: 22.1 vs 16.6 months*
BRCA MUT:
PFS: 37.2 vs 21.7 months*
HRD-pos (incl BRCA MUT):
PFS: 37.2 vs 17.1 months*

abs Oct 2019

NCT02655016; PRIMA III Niraparib 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:
PFS: 13.8 vs 8.2 month*
HRD-positive:
PFS: 21.9 vs 10.4 months*

pub 2019

*Statistically significant result

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
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

Nir vs Placebo:

non-gBRCA MUT:
PFS: 9.3 vs 3.9 months*
gBRCA MUT:
PFS: 21.0 vs 5.5 months*
HRD-neg:
PFS: 6.9 vs 3.8 months*
HRD-pos (BRCA WT):
PFS: 9.3 vs 3.7 months*

pub 2016

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 with olaparib (tablets) maintenance treatment in gBRCA MUT patients

Ola vs Placebo:

PFS: 30.2 vs 5.5 months*

pub 2017

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, but most active in BRCA MUT

Ruc vs Placebo:

All:
PFS: 13.7 vs 5.4 months*
BRCA WT/LOH low:
PFS: 8.2 vs 5.3 months*
BRCA WT/LOH high:
PFS: 11.1 vs 5.6 months*
BRCA MUT:
PFS: 26.8 vs 5.4 months*

pub 2017

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:
PFS: 8.4 vs 4.8 months*
OS: 29.8 vs 27.8 months*
BRCA WT:
PFS: 7.4 vs 5.5 months*
OS: 24.5 vs 26.6 months
BRCA MUT:
PFS: 11.2 vs 4.3 months*
OS: 34.9 vs 30.2 months*

pub 2012; 2014; 2016

*Statistically significant result

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 gBRCA MUT patients

ORR: 46%
PFS: 9.4 months

pub 2016

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 Apr 2018

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 non-platinum chemotherapy

Ola vs TPC:

ORR: 72 vs 51%*
PFS: 13.4 vs 9.2 months*

abs Jun 2019

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:
ORR: 76 vs 32%*
PFS: 23.7 vs 5.7 months*
OS: 37.8 vs 23.0 months*

gBRCA MUT:
ORR: 83 vs 63%
PFS: 16.4 vs 16.5 months
OS: 44.2 vs 40.1 months

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 cancer

ORR: 35%
PFS: 11.0 months

pub 2015

NCT01891344; ARIEL2 Part1 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 Part1)

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%*
PFS: 12.8 vs 5.7 vs 5.2 months*

pub 2017

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

NCT02354131; AVANOVA II Bevacizumab, Niraparib 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 activity of niraparib+bevacizumab

Nir+Bev vs Nir:

ORR: 62 vs 30%
PFS: 11.9 vs 5.5 months

pub 2019

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 promising activity in late-line treatment setting

BRCA MUT:
ORR: 39%

HRD-positive (incl. BRCA MUT):
ORR: 26%

pub 2019

NCT02734004 I/II Durvalumab, Olaparib 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 patients

ORR: 71.9%
DCR (7 months): 65.6%
PFS: 11.1 months

abs Oct 2019

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 patients

ORR: 44%
DCR: 63%

pub 2019

*Statistically significant result

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 gBRCA MUT patients

ORR: 30%
PFS: 5.5 months

pub 2016

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 Apr 2018

Drugs in Clinical Development
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 cancer

ORR: 20%
PFS: 5.8 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:
ORR: 18%

gBRCA MUT:
ORR: 60% (n=5)

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 promising activity in late-line treatment setting

BRCA MUT:
ORR: 27%

HRD-positive (incl. BRCA MUT):
ORR: 10%

pub 2019

NCT03314740; BAROCCO II Cediranib, Olaparib, Paclitaxel 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.

Olaparib+cediranib (continuous dosing) shows a promising trend towards improved PFS in comparison with weekly paclitaxel, in particular in BRCA WT patients

Ola+Ced (continuous) vs Ola+Ced (intermittent) vs Pac:

gBRCA WT:
PFS: 5.8 vs 3.8 vs 2.1 months

abs Oct 2019

NCT02657889; TOPACIO I/II Niraparib, Pembrolizumab 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 independent of BRCA status, HRD status and PD-L1 expression

ORR: 18%

pub 2019

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 patients

ORR: 22%
DCR: 50%

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 olaparib+alpelisib combination in gBRCA WT patients

ORR: 36%
PFS: 7.2 months

gBRCA WT:
ORR: 35%

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
NCT02484404 I/II Cediranib, Durvalumab, Olaparib 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

Promising response rates for olaparib, cediranib and durvalumab combinations independent of PD-L1 levels

Ola+Dur:
ORR: 15%
DCR (4 months): 53%

Phase I:
Ola+Ced+Dur:
ORR: 29% (n=7)

pub 2017; abs Sep 2017; Oct 2018

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 cancer

ORR: 41.7% (n=12)
PFS: 9.1 months

pub 2017

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 increased PFS without additional toxicity

Ber+Gem vs Gem:

PFS: 5.7 vs 3.7 months*

abs Oct 2019

*Statistically significant result

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