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

3 Prior Therapies

Cell Cycle Inhibitors: CHK1/2 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

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

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

ORR: 6%
PFS: 3.1 months

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+ ovarian cancer with 25% achieving PFS for 23 weeks or longer, but greatest benefit is seen in low grade serous (LGS) ovarian cancer

ORR (HGS): 0%
ORR (LGS): 100% (n=3)
PFS ≥ 23 weeks: 25%

abs May 2019 and presentation

Cell Cycle Inhibitors: CHK1/2 Inhibitors

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 Prexasertib 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

ORR: 43%
PFS: 5.3 months

pub 2016

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 2021

*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 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:
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 ovarian BRCA MUT after PARPi failure:
ORR: 3.3%
DCR: 77%
PFS: 3.9 month

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

abs Mar 2019

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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