Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Olaparib and Temozolomide
Olaparib · 4 trials · 4 indications
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS using RECIST 1.1 as assessed by BICR is presented.
OS will be measured from the date of first dose until death or end of follow-up. All subjects who receive at least one dose of the 3-drug combination will be included. Subjects who discontinue treatment prior to Cycle 2 will not be included in the analysis. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which that patient was known to be alive. Estimation based on the Kaplan-Meier curve.
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The ORR for all participants will be presented by biomarker subgroup.
ORR was defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response was assessed based on PCWG-modified RECIST 1.1 criteria (CR: soft tissue CR with no evidence of disease \[NED\] on bone scan; PR: soft tissue PR with non-progressive disease, non-evaluable \[NE\], or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan). Per protocol, RECIST 1.1 was modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR as assessed by BICR is presented.
| Arm | Type | Description |
|---|---|---|
| Olaparib + bevacizumab | EXPERIMENTAL | Participants will receive olaparib (300 mg twice daily \[BID\] oral) + Bevacizumab (5 mg/kg intravenous \[IV\] once every 2 weeks \[Q2W\]) until progressive disease or end of study. |
| Olaparib | EXPERIMENTAL | Participants will receive olaparib (300 mg BID) oral, until progressive disease or end of study. |
| Bevacizumab + chemotherapy | ACTIVE_COMPARATOR | Participants will receive investigator's choice of either bevacizumab (7.5 mg/kg IV once every three weeks (Q3W)) + capecitabine (1000 mg/m\^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5-FU (400 mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study. |
| Cohort 1 - Measurable Disease | EXPERIMENTAL | All Participants will receive Paclitaxel, Olaparib and Pembrolizumab. |
| Arm 2: Cohort 2-Unmeasurable Disease | EXPERIMENTAL | All Participants will receive Paclitaxel, Olaparib and Pembrolizumab. |
| Olaparib+Pembrolizumab | EXPERIMENTAL | Participants receive olaparib 300 mg via oral tablet 2 times each day PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 21-day cycle. Participants may receive olaparib+pembrolizumab for up to approximately 2 years. |
| Cohort 1: BRCA1/2 Mutated | EXPERIMENTAL | Per protocol, participants with tumors that harbor known or suspected deleterious mutations in breast cancer susceptibility gene 1 or gene 2 (BRCA1/2) based on the Lynparza homologous recombination repair-homologous recombination deficiency (HRR-HRD) Assay, excluding breast and ovarian cancers, were considered BRCA1/2 mutated and enrolled into Cohort 1: BRCA1/2. Participants with known or suspected deleterious mutations in BRCA1/BRCA2 were enrolled into Cohort 1 whether or not they were homologous recombination repair mutated (HRRm) positive for the other protocol specified genes in the Lynparza HRR-HRD Assay, or whether they had loss of heterozygosity (LOH) protocol specified score of ≥16. Participants in Cohort 1: BRCA1/2 received oral olaparib, 300 mg twice daily (BID) continuously until documented disease progression or discontinuation criteria were met. |
| Cohort 2: HRD+, HRR Non-mutated | EXPERIMENTAL | Per protocol, participants with tumors that do NOT have any known or suspected deleterious mutations in BRCA1/2, or any of the other protocol specified genes in the Lynparza HRR-HRD Assay (BRCA1/2 Non-mutated/HRR Non-mutated) but had a loss of heterozygosity (LOH) score greater than or equal to the protocol specified cutoff of 16, were considered homologous recombination deficiency positive (HRD+) and enrolled into Cohort 2: HRD+(BRCA1/2 non-mutated/HRR Non-mutated). Participants in Cohort 2: HRD+ (BRCA1/2 Non-mutated/HRR Non-mutated) received oral olaparib, 300 mg BID continuously until documented disease progression or discontinuation criteria were met. |
| Cohort 2: HRRm, BRCA1/2 Non-mutated | EXPERIMENTAL | Per protocol, participants with tumors that do NOT have any known or suspected deleterious mutations in BRCA1/2 but have known or suspected deleterious mutations in any of the other protocol specified genes in the Lynparza HRR-HRD Assay were considered homologous recombination repair mutated \[HRRm\] and were enrolled into Cohort 2: HRRm (BRCA1/2 Non-mutated). Participants in Cohort 2: HRRm (BRCA1/2 Non-mutated) received oral olaparib, 300 mg BID continuously until documented disease progression or discontinuation criteria were met. |
| Cohort 3: sBRCAm Breast Cancer | EXPERIMENTAL | Per protocol, participants with breast cancer tumors that harbor known or suspected deleterious somatic mutations in BRCA1/2 and do not harbor a germline BRCA1/2 mutation were enrolled into Cohort 3: somatic BRCA1/2 mutations (sBRCAm). Participants in Cohort3: sBRCAm Breast Cancer received oral olaparib, 300 mg BID continuously until documented disease progression or discontinuation criteria were met. |
| Name | Type | Description |
|---|---|---|
| Olaparib | DRUG | 300 mg BID, oral until progressive disease or end of study |
| 5-FU | DRUG | 2400 mg/m\^2 over 46 to 48 hours Q2W IV infusion until disease progression or end of study; bolus 5-FU (400mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion |
| Bevacizumab | DRUG | 5 mg/kg or 7.5 mg/kg Q2W or Q3W IV infusion until progressive disease or end of study |
| Capecitabine | DRUG | 1000 mg/m\^2 oral capsule BID for 14 days, then 7 days off, Q3W) until progressive disease or end of study |
| Leucovorin/ levoleucovorin | DRUG | 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) may be added to Bevacizumab + 5-FU per investigator's discretion Q2W IV infusion until progressive disease or end of study |
| Paclitaxel | DRUG | 1. Patients will receive treatment on Day 1 and 8 starting with cycle 2. 2. Paclitaxel (80 mg) will be administered IV on days 1 and 8 starting with cycle 2 (every 21 days). 3. Drug - Paclitaxel - 80mg IV |
| Pembrolizumab | DRUG | 1. Patients will receive treatment every 21 days. 2. Pembrolizumab (200 mg) will be administered IV on day 1 (every 21 days). 3. Drug - 200mg IV |
Inclusion Criteria: 1. Has a histologically-confirmed metastatic or unresectable (Stage IV as defined by American Joint Committee on Cancer (AJCC eighth edition) colorectal adenocarcinoma (National Comprehensive Cancer Network \[NCCN\] 2018). 2. Has not progressed (ie, achieved a stable disease \[S...
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Olaparib is an investigational small molecule being studied in oncology for advanced solid neoplasms, solid tumors, advanced gastric adenocarcinoma, and metastatic colorectal cancer. It is a PARP inhibitor targeting PARP1, PARP2, and PARP3. Olaparib is in Phase 2 clinical development for these indications.
Olaparib targets PARP1, PARP2, and PARP3, which are poly (ADP-ribose) polymerase enzymes involved in DNA repair. As an inhibitor of these targets, Olaparib is being studied in biomarker-selected cancers with homologous recombination repair mutations or homologous recombination deficiency.
Olaparib is being developed by Merck & Company, Inc., which trades under the ticker MRK. The company is conducting clinical trials of Olaparib in advanced solid tumors and other oncology indications.
Olaparib is in Phase 2 clinical development for advanced solid neoplasms, solid tumors, and advanced gastric adenocarcinoma. It is also being studied in a Phase 3 trial for metastatic colorectal cancer. Olaparib remains investigational and is not yet approved for these uses.
Olaparib is being studied in several clinical trials, including NCT03742895 for advanced solid neoplasms, NCT04123366 for solid tumors, NCT04209686 for advanced gastric adenocarcinoma, and NCT04456699 for metastatic colorectal cancer. These trials are Phase 2 or Phase 3 and are active or completed.
Olaparib is also known as Olaparib 400 mg, Olaparib 300 mg BID, and Olaparib and Temozolomide. These names refer to the same drug, Olaparib, which is being developed by Merck & Company, Inc. for various advanced cancer indications.