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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001202-42 | EudraCT Number |
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Study design This is a Phase II, open-label, multi-drug, multi-center, multi-arm, signal-searching study in patients with extensive-stage small-cell lung cancer (SCLC) who have refractory or resistant disease from prior platinum-based chemotherapy.
This study is modular in design, allowing evaluation of the preliminary efficacy, safety, tolerability, and immunogenicity of novel combinations of immunotherapies and/or deoxyribonucleic acid (DNA) damage repair inhibitors in patients with platinum refractory or resistant extensive-stage-disease SCLC. Patients who have progressive disease (PD) during first-line platinum-based chemotherapy (platinum refractory) or PD within 90 days after completing first-line platinum-based chemotherapy (platinum resistant) will be enrolled to the study. The primary objective of the study is to assess the preliminary efficacy of each treatment arm based on objective response rate (ORR).
This study consists of a number of arms (sub-studies), each evaluating the efficacy, safety, and tolerability of a specific agent or combination. This study was initially open with 2 arms (Arms A and B), and additional arms may open, provided there is compelling rationale for the combination and safe and tolerable doses and schedules have been determined from ongoing Phase I studies. There are 2 pre-defined arms:
A. Durvalumab + tremelimumab followed by durvalumab monotherapy B. AZD1775 + carboplatin (CBDP)
Further arm was added in amendment 3:
C. AZD6738 + olaparib Amendment #4 was updated with possibility to allow expansion of any arm, to a total of 40 eligible subjects, based on Review Committee assessment of data from the first 20 subjects (from Stage 1 and Stage 2). Currently Arm A will enroll 20 additional patients into expansion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARM A | Experimental |
| |
| ARM B | Experimental |
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| ARM C | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Durvalumab and Tremelimumab | Drug | Durvalumab + tremelimumab via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy via IV infusion q4w, starting on Week 16 until PD, or for other discontinuation criteria. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Overall Response | Overall Response Rate (ORR) using Investigator assessments according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. ORR was defined as the number (percentage) of participants with a confirmed Complete Response (CR) or confirmed Partial Response (PR) and was estimated for each treatment arm with corresponding 2-sided 95% exact confidence intervals (CIs). A confirmed response of CR/PR meant that a response of CR/PR was recorded at one visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit, and not less than 4 weeks after the visit when the response was first observed, with no evidence of progression between the initial and CR/PR confirmation visit. | Until disease progression [PD] (Up to 3.5 Years) |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Response (DoR) | The DoR was defined as the time from the date of first documented response (which was subsequently confirmed) CR/PR until the date of documented progression, or death in the absence of disease progression. The DoR in participants with confirmed objective response are reported. | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
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Inclusion criteria (applicable to all arms)
Inclusion criteria (Arm A specific)
Inclusion criteria (Arm B specific) • Able and willing to swallow oral medication.
Inclusion criteria (Arm C specific)
• Able and willing to swallow oral medication.
Exclusion criteria (applicable to all arms):
Exclusion criteria (Arm A specific)
Exclusion criteria (Arm B specific)
Exclusion criteria (Arm C specific)
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| Name | Affiliation | Role |
|---|---|---|
| Haiyi Jiang, M.D. | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Gauting | 82131 | Germany | |||
| Research Site |
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| Label | URL |
|---|---|
| Related Info | View source |
| Related Info | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Participants who met the inclusion exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
The study was conducted between 28-Nov-2016 and 22-Jun-2020, at 11 study centers in 5 countries (Germany, Hungary, Poland, Spain, and Ukraine).
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Durvalumab + Tremelimumab (Original Cohort) | Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed progressive disease (PD), or other discontinuation criteria. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 16, 2020 | Jun 10, 2021 |
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| AZD1775 and carboplatin (CBPT) | Drug | AZD1775 twice daily (oral) for 2.5 days from Day 1 + CBDP area under the curve 5 (Day1) (IV); every 3 weeks. |
|
| AZD6738 and olaparib | Drug | AZD6738 once a day (oral) for 7 days from Day 1 + olaparib twice a day(oral) for 28 days from Day 1, every 4 weeks |
|
| Percentage of Participants With Disease Control at 12 Weeks | The disease control rate (DCR) at 12 weeks was defined as the percentage of participants who had a best objective response of CR or PR in the first 13 weeks or who had demonstrated stable disease (SD) for a minimum interval of 11 weeks following the start of study treatment. The DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. | At 12 Weeks |
| Time to Response (TTR) | The TTR (per RECIST 1.1 as assessed by the Investigator) was defined as the time from the date of first dose until the first date of documented response. | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
| Progression Free Survival (PFS) | The PFS (per RECIST 1.1 according to the Investigator's assessment) was defined as the time from the date of the first dose of study treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from allocated therapy or received another anti-cancer therapy prior to progression. | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
| Overall Survival (OS) | The OS was defined as the time from the date of the first dose of study treatment until death due to any cause. | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
| Time to Maximum Concentration (Tmax) | Time to maximum concentration for ceralasertib and olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) |
| Maximum Concentration (Cmax) | Maximum concentration for ceralasertib and olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) |
| Partial Area Under the Concentration-time Curve (AUC0-6) | Partial area under the concentration-time curve for ceralasertib and olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose) |
| Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) | Area under the concentration-time curve from time zero to the last measurable concentration for Ceralasertib and Olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose) |
| Time to Maximum Concentration at Steady State (Tmax,ss) | Time to maximum concentration at steady state for Ceralasertib and Olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
| Maximum Concentration at Steady State (Cmax,ss) | Maximum concentration at steady state for Ceralasertib and Olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
| Minimum Concentration at Steady State (Cmin,ss) | Minimum concentration at steady state for Ceralasertib and Olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
| Area Under the Concentration-time Curve at Steady State (AUCss) | Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
| Apparent Clearance of Drug at Steady State at Steady State (CLss/F) | Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported. | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
| Serum Concentrations of Durvalumab and Tremelimumab | Serum concentrations of Durvalumab and Tremelimumab are reported. | Durvalumab: Cycle 1 (each cycle was 4 weeks) Day 1(post-dose); Cycle 2 Day 1(pre-dose); Cycle 5 Day 1 (pre-dose); Tremelimumab: Cycle 1 (each cycle was 4 weeks) Day 1 (post-dose); Cycle 2 Day 1 (pre-dose); Cycle 5 Day 1 (No dose); Cycle 7 Day 1 (No dose) |
| Plasma Concentrations of Adavosertib and Carboplatin | Plasma concentrations of Adavosertib and Carboplatin are reported. | Adavosertib: Cycle 1 (each cycle was 21 days) Day 3 (pre-dose and post-dose); Cycle 3 Day 3 (pre-dose and post-dose); Carboplatin: Cycle 1 (each cycle was 21 days) Day 1 (post-dose) |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event. | Day 1 until disease progression, and follow-up visit (Up to 3.5 Years) |
| Kecskemét |
| 6000 |
| Hungary |
| Research Site | Miskolc | 3529 | Hungary |
| Research Site | Székesfehérvár | 8000 | Hungary |
| Research Site | Törökbálint | 2045 | Hungary |
| Research Site | Poznan | 60-569 | Poland |
| Research Site | Warsaw | 02-781 | Poland |
| Research Site | Seville | 41009 | Spain |
| Research Site | Valencia | 46009 | Spain |
| Research Site | Dnipro | 49102 | Ukraine |
| Research Site | Ivano-Frankivsk | 76018 | Ukraine |
| Research Site | Sumy | 40022 | Ukraine |
| CSR Synopsis | View source |
| FG001 | Arm A: Durvalumab + Tremelimumab (Expansion Cohort) | Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed PD, or other discontinuation criteria. |
| FG002 | Arm B: Adavosertib + Carboplatin | Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w). |
| FG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
| COMPLETED |
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| NOT COMPLETED |
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|
The Full Analysis Set (FAS) included all treated participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Durvalumab + Tremelimumab (Original Cohort) | Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed progressive disease (PD), or other discontinuation criteria. |
| BG001 | Arm A: Durvalumab + Tremelimumab (Expansion Cohort) | Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed PD, or other discontinuation criteria. |
| BG002 | Arm B: Adavosertib + Carboplatin | Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w). |
| BG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Overall Response | Overall Response Rate (ORR) using Investigator assessments according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. ORR was defined as the number (percentage) of participants with a confirmed Complete Response (CR) or confirmed Partial Response (PR) and was estimated for each treatment arm with corresponding 2-sided 95% exact confidence intervals (CIs). A confirmed response of CR/PR meant that a response of CR/PR was recorded at one visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit, and not less than 4 weeks after the visit when the response was first observed, with no evidence of progression between the initial and CR/PR confirmation visit. | The FAS included all treated participants. | Posted | Count of Participants | Participants | Until disease progression [PD] (Up to 3.5 Years) |
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| Secondary | Duration of Response (DoR) | The DoR was defined as the time from the date of first documented response (which was subsequently confirmed) CR/PR until the date of documented progression, or death in the absence of disease progression. The DoR in participants with confirmed objective response are reported. | The FAS included all treated participants. | Posted | Median | Full Range | Months | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
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| Secondary | Percentage of Participants With Disease Control at 12 Weeks | The disease control rate (DCR) at 12 weeks was defined as the percentage of participants who had a best objective response of CR or PR in the first 13 weeks or who had demonstrated stable disease (SD) for a minimum interval of 11 weeks following the start of study treatment. The DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. | The FAS included all treated participants. | Posted | Number | Percentage of Participants | At 12 Weeks |
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| Secondary | Time to Response (TTR) | The TTR (per RECIST 1.1 as assessed by the Investigator) was defined as the time from the date of first dose until the first date of documented response. | The FAS included all treated participants. | Posted | Median | Full Range | Months | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
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| Secondary | Progression Free Survival (PFS) | The PFS (per RECIST 1.1 according to the Investigator's assessment) was defined as the time from the date of the first dose of study treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from allocated therapy or received another anti-cancer therapy prior to progression. | The FAS included all treated participants. | Posted | Median | 95% Confidence Interval | Months | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
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| Secondary | Overall Survival (OS) | The OS was defined as the time from the date of the first dose of study treatment until death due to any cause. | The FAS included all treated participants. | Posted | Median | 95% Confidence Interval | Months | Until disease progression or data cut-off or Death (Up to 3.5 Years) |
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| Secondary | Time to Maximum Concentration (Tmax) | Time to maximum concentration for ceralasertib and olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. | Posted | Median | Full Range | Hour | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) |
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| Secondary | Maximum Concentration (Cmax) | Maximum concentration for ceralasertib and olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) |
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| Secondary | Partial Area Under the Concentration-time Curve (AUC0-6) | Partial area under the concentration-time curve for ceralasertib and olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. Here, number analyzed in each row signifies only participants with available data that were analyzed for that specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose) |
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| Secondary | Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) | Area under the concentration-time curve from time zero to the last measurable concentration for Ceralasertib and Olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. Here, number analyzed in each row signifies only participants with available data that were analyzed for that specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose) |
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| Secondary | Time to Maximum Concentration at Steady State (Tmax,ss) | Time to maximum concentration at steady state for Ceralasertib and Olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. | Posted | Median | Full Range | Hour | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
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| Secondary | Maximum Concentration at Steady State (Cmax,ss) | Maximum concentration at steady state for Ceralasertib and Olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
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| Secondary | Minimum Concentration at Steady State (Cmin,ss) | Minimum concentration at steady state for Ceralasertib and Olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
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| Secondary | Area Under the Concentration-time Curve at Steady State (AUCss) | Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
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| Secondary | Apparent Clearance of Drug at Steady State at Steady State (CLss/F) | Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | Litre/hour | Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose) |
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| Secondary | Serum Concentrations of Durvalumab and Tremelimumab | Serum concentrations of Durvalumab and Tremelimumab are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. Here, number analyzed in each row signifies only participants with available data that were analyzed for that specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Durvalumab: Cycle 1 (each cycle was 4 weeks) Day 1(post-dose); Cycle 2 Day 1(pre-dose); Cycle 5 Day 1 (pre-dose); Tremelimumab: Cycle 1 (each cycle was 4 weeks) Day 1 (post-dose); Cycle 2 Day 1 (pre-dose); Cycle 5 Day 1 (No dose); Cycle 7 Day 1 (No dose) |
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| Secondary | Plasma Concentrations of Adavosertib and Carboplatin | Plasma concentrations of Adavosertib and Carboplatin are reported. | Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study treatment and had post-dose data available, excluding those who had a deviation considered by the sponsor to have a potential impact on the interpretation of the pharmacokinetic analyses. Here, number analyzed in each row signifies only participants with available data that were analyzed for that specified time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | Adavosertib: Cycle 1 (each cycle was 21 days) Day 3 (pre-dose and post-dose); Cycle 3 Day 3 (pre-dose and post-dose); Carboplatin: Cycle 1 (each cycle was 21 days) Day 1 (post-dose) |
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| Secondary | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event. | The FAS included all treated participants. | Posted | Count of Participants | Participants | Day 1 until disease progression, and follow-up visit (Up to 3.5 Years) |
|
Day 1 until disease progression, and follow-up visit (Up to 3.5 Years)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Durvalumab + Tremelimumab (Original Cohort) | Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed progressive disease (PD), or other discontinuation criteria. | 19 | 21 | 6 | 21 | 14 | 21 |
| EG001 | Arm A: Durvalumab + Tremelimumab (Expansion Cohort) | Participants received durvalumab 1500 mg + tremelimumab 75 mg via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy 1500 mg via IV infusion q4w, starting on Week 16 until confirmed PD, or other discontinuation criteria. | 16 | 20 | 8 | 20 | 16 | 20 |
| EG002 | Arm B: Adavosertib + Carboplatin | Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w). | 10 | 10 | 4 | 10 | 8 | 10 |
| EG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. | 15 | 21 | 7 | 21 | 13 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Myasthenic syndrome | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Enterocolitis haemorrhagic | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Burns third degree | Injury, poisoning and procedural complications | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Haematotoxicity | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 23.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hyperchloraemia | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Lumbosacral radiculopathy | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Nephritis | Renal and urinary disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Influenza | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Skin induration | Skin and subcutaneous tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Peripheral sensorimotor neuropathy | Nervous system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Psoriatic arthropathy | Musculoskeletal and connective tissue disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 23.0 | Non-systematic Assessment |
| |
| Urinary hesitation | Renal and urinary disorders | MedDRA version 23.0 | Non-systematic Assessment |
|
Study results are Sponsor's intellectual property and PIs cannot present or publish results without prior Sponsor approval.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 12, 2019 | Jun 16, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000613593 | durvalumab |
| C520704 | tremelimumab |
| C549567 | adavosertib |
| D016190 | Carboplatin |
| C000611951 | ceralasertib |
| C531550 | olaparib |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
Not provided
Not provided
| ≥ 50 to < 65 |
|
| ≥ 65 to < 75 |
|
| ≥ 75 to < 80 |
|
| ≥ 80 |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w). |
| OG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
|
|
| OG002 |
| Arm B: Adavosertib + Carboplatin |
Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w). |
| OG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
|
|
| OG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
|
|
| OG002 |
| Arm B: Adavosertib + Carboplatin |
Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w). |
| OG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
|
|
| OG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
|
|
|
|
|
| Participants |
|
|
|
|
|
|
|
|
|
| OG002 | Arm B: Adavosertib + Carboplatin | Participants orally received adavosertib 225 mg twice daily (BID) for 2.5 days from Day 1 + carboplatin area under the curve (AUC) 5 Day 1 IV, every 3 weeks (q3w). |
| OG003 | Arm C: Ceralasertib (AZD6738) + Olaparib | Participants orally received ceralasertib 160 mg once daily (QD) Days 1 to 7 + olaparib 300 mg BID Days 1 to 28, q4w. |
|
|