Drug Class: Cell Cycle Inhibitors

Cell Cycle Inhibitors: AURKA/B

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

2 Prior Therapies

Cell Cycle Inhibitors: CDK4/6 Inhibitors

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

1 Prior Therapy 3 Prior Therapies

Cell Cycle Inhibitors: CHK1/2 Inhibitors

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

3 Prior Therapies

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

5 Prior Therapies

Cell Cycle Inhibitors: p53 Activators

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

Prior Therapies Not Reported

Cell Cycle Inhibitors: Wee1 Inhibitors

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

1 Prior Therapy 2 Prior Therapies 3 Prior Therapies

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

4 Prior Therapies 5 Prior Therapies 6 Prior Therapies 7 Prior Therapies Prior Therapies Not Reported

Cell Cycle Inhibitors: AURKA/B

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
NCT01091428 I/II Alisertib, Paclitaxel Randomized Phase 2 Study of MLN8237, an Aurora A Kinase Inhibitor, Plus Weekly Paclitaxel or Weekly Paclitaxel Alone in Patients With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, Preceded by a Phase 1 Portion in Patients With Ovarian or Breast Cancer

Alisertib+paclitaxel shows promising increase in PFS compared to paclitaxel alone, with a manageable safety profile

Ali+Pac vs Pac:

ORR: 48 vs 37%
PFS: 7.6 vs 5.1 months

pub 2019

Cell Cycle Inhibitors: CDK4/6 Inhibitors

Neo adjuvant (before surgery) and 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
NCT03531645 II Abemaciclib, Fulvestrant A Pilot Phase II Study of Neoadjuvant Fulvestrant Plus Abemaciclib in Women With Advanced Low Grade Serous Carcinoma

Neoadjuvant treatment with fulvestrant and abemaciclib is tolerable and demonstrates unprecedented response and complete gross resection rates in Low Grade Serous OC

ORR: 60% (n=15)
DCR: 100%

7 patients w/ IDS:
100% achieved optimal cytoreduction at IDS
(71% R0, 29% R1)

abs Jun 2022 and poster

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
NCT01536743 II Palbociclib A Open Label Phase II Study of the Efficacy and Safety of PD0332991 a Selective Inhibitor of the Cyclin Dependent Kinases 4 and 6 in Patients With Recurrent Ovarian Cancer Demonstrating Rb-proficiency and Low p16 Expression

Palbociclib has modest single agent activity in unselected patients, but shows encouraging activity in patients with CDKN2A loss or CDK6 AMP

ORR: 6%
PFS: 3.1 months

6 patients w/ response by CA125 or RECIST:
1 w/ CDKN2A loss, 1 w/CDKN2A loss and CCNE AMP, 1 w/ CDK6 AMP and NRAS AMP and BRAF AMP

abs Jun 2016 and poster

NCT02657928 II Letrozole, Ribociclib A Phase 2 Trial of Ribociclib (LEE011) and Letrozole in ER Positive Relapsed Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinomas, and Endometrial Cancers.

Ribociclib+letrozole is active in ER+ OC with 25% achieving PFS for 23 weeks or longer, but greatest benefit is seen in LGSOC

ORR (HGSOC): 0%
ORR (LGSOC): 100% (n=3)
PFS ≥ 23 weeks: 25%

abs May 2019 and presentation

NCT03673124 II Letrozole, Ribociclib A Phase II Trial of Ribociclib (LEE011) Plus Letrozole in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube or Peritoneum

The combination of letrozole plus ribociclib demonstrates promising activity in women with recurrent LGSOC

ORR: 23%
DCR: 79%
DoR: 19.1 months
PFS: 19.1 months

abs Mar 2023 and presentation

Cell Cycle Inhibitors: CHK1/2 Inhibitors

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
NCT03414047 II ACR-368 A Phase 2 Study of Prexasertib in Platinum-Resistant or Refractory Recurrent Ovarian Cancer

ACR-368 (prexasertib) demonstrates durable single agent activity in a subset of patients with platinum resistant HGSOC regardless of clinical characteristics or prior therapy

ORR: 12.1%
DCR: 37.1%

pub 2022

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
NCT02203513 II ACR-368 A Phase II Single Arm Pilot Study of the Chk1/2 Inhibitor (LY2606368) In BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Triple Negative Breast Cancer, and High Grade Serous Ovarian Cancer

Promising activity in heavily pretreated BRCA WT patients, including those with CCNE1 alterations, but modest activity in BRCA MUT patients

BRCA WT:
ORR: 32%
PFS: 7.5 months

BRCA MUT
ORR: 11.1%

pub 2018, abs May 2020 and poster

Cell Cycle Inhibitors: p53 Activators

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
Drugs in Clinical Development
NCT02098343 II Carboplatin, Liposomal doxorubicin, Eprenetapopt PiSARRO: p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

Encouraging activity of APR-246+carboplatin+liposomal doxorubicin in TP53-mutated Pt-S and partially Pt-S patients

ORR: 62%
PFS: 10.5 months

abs Jun 2016

Cell Cycle Inhibitors: Wee1 Inhibitors

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
Drugs in Clinical Development
NCT01357161 II Adavosertib, Carboplatin, Paclitaxel A Randomized, Phase II Study Evaluating MK-1775 in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Adult Patients With Platinum Sensitive p53 Mutant Ovarian Cancer

Improved PFS with addition of AZD1775

Ada+CarboPt+Pac vs CarboPt+Pac:

ORR: 81.4 vs 75.8%
PFS: 7.9 vs 7.3 months

pub 2020

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
NCT01164995 II Adavosertib, Carboplatin Phase II Pharmacological Study With Wee-1 Inhibitor MK-1775 Combined With Carboplatin in Patients With p53 Mutated Epithelial Ovarian Cancer and Early Relapse (< 3 Months) or Progression During Standard First Line Treatment

Promising activity of adavosertib+carboplatin combination in TP53-mutated primary platinum resistant and platinum refractory ovarian cancer; a large proportion of responding patient had CCNE1 AMP

ORR: 41%
PFS: 5.6 months

pub 2016, pub 2023

NCT02101775 II Adavosertib, Gemcitabine A Randomized Placebo-Controlled Phase II Trial Comparing Gemcitabine Monotherapy to Gemcitabine in Combination With AZD 1775 (MK 1775) in Women With Recurrent, Platinum Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers

Addition of adavosertib to gemzar improves ORR, PFS and OS

Gem+Ada vs Gem:

ORR: 25 vs 7%
PFS: 4.6 vs 3.0 months*
OS: 11.4 vs 7.2 months*

pub 2021

NCT02272790 II Adavosertib, Carboplatin A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Adavosertib+carboplatin shows efficacy in primary platinum resistant ovarian cancer with greatest benefit in patients receiving adavosertib weeks 1–3+carboplatin, but with increased hematologic toxicity

Ada week 1+CarboPt:
ORR: 30.4%
PFS: 4.2 months

Ada week 1-3+CarboPt
ORR: 66.7% (n=12)
PFS: 12.0 months (n=12)

pub 2022

NCT04516447 I Azenosertib, Carboplatin, Gemcitabine, Liposomal doxorubicin, Paclitaxel A Phase 1b Study of ZN-c3 in Combination With Chemotherapy in Patients With Platinum-Resistant Ovarian, Peritoneal or Fallopian Tube Cancer

Azenosertib (ZN-c3), combined with chemotherapy, is well-tolerated and demonstrates clinical activity in patients with Pt-R or Pt-Rf OC

Aze+CarboPt:
ORR: 35.7%; DoR: 11.4 months; PFS: 10.4 months

Aze+Pac:
ORR: 50%; DoR: 5.6 months; PFS: 7.4 months

Aze+Gem: (n=13)
ORR: 38.5%; DoR: 6.2 months; PFS: 8.3 months

Aze+PLD:
ORR: 19.4%; DoR: 7.3 months; PFS: 6.3 months

abs Jun 2023 and poster

*Statistically significant result

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
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 OC 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:
Ada+Ola vs Ada (n=15): ORR: 19 vs 20%; DoR: 6.4 vs 5.6 months; DCR (4 months): 81 vs 67%; PFS: 5.6 vs 5.6 months

BRCA WT:
Ada+Ola vs Ada: ORR: 39 vs 31%; DoR: 8.7 vs 4.1 months; DCR (4 months): 94 vs 69%; PFS: 8.4 vs 4.1 months

abs Jun 2021 and presentation

NCT02482311 Ib Adavosertib A Phase Ib, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumour Activity of AZD1775 Monotherapy in Patients With Advanced Solid Tumours

Adavosertib is well tolerated and shows preliminary antitumor activity. No clear correlation between genomic profile and clinical response

30 OC BRCA MUT after PARPi failure:
ORR: 3.3%
DCR: 77%
PFS: 3.9 month

16 OC BRCA WT:
ORR: 6.3%
DCR: 69%
PFS: 4.5 months

pub 2023

NCT02511795 Ib Adavosertib, Olaparib A Phase Ib Study of AZD1775 and Olaparib in Patients With Refractory Solid Tumours

Adavosertib+olaparib shows anti-tumor activity in ovarian cancer, particularly at the twice daily (BID) schedule

ORR: 15%
DCR: 85%
SD responses seen in 2 patients with CCNE1 AMP

abs Apr 2019 and poster

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