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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-000124-34 | EudraCT Number |
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Available clinical data has shown limited anti-tumor activity and reaching target study drug dose levels may not be feasible.
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This Phase 1b/2 study will examine the effects of the study drugs, avelumab, binimetinib and talazoparib when given in a 2 (doublet) or 3 (triplet) drug combination, in patients with locally advanced or metastatic RAS-mutant solid tumors. The Phase 1b part of the study will assess if the different study drugs can be given together safely and which doses to use for further research. Phase 2 will test if the study treatments have an effect on tumor size and growth, and gather more information about potential side effects.
This is a Phase 1b/2, open label, multi-center, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of combinations of avelumab, binimetinib and talazoparib in adult patients with metastatic pancreatic ductal adenocarcinoma and other locally advanced or metastatic KRAS- or NRAS-mutant solid tumors.
The Phase 1b part of this study will initially assess doublet drug combinations to determine a recommended dose for further investigation. Following this, the recommended dose for the combination of avelumab, binimetinib and talazoparib (triplet) will be determined. The recommended doses for the doublet and triplet combinations will be used in the Phase 2 part of the study, which will assess the safety and preliminary anti-tumor activity of the study treatments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Avelumab and binimetinib | Experimental | Open label |
|
| Avelumab, binimetinib and talazoparib | Experimental | Open label |
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| Binimetinib and talazoparib. | Experimental | Open label. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Avelumab | Drug | IV treatment |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) During the Primary DLT Evaluation Period (Cycle 1) in Phase 1b | Any adverse events (AEs) occurring in the first cycle of treatment (28 days) which were attributable to study drugs and met DLT criteria. DLT was defined as hematologic: Grade 4 neutropenia lasting>5 days; febrile neutropenia; neutropenic infection; Grade >=3 thrombocytopenia with bleed; Grade 4 thrombocytopenia; Grade 4 anemia; non-hematologic: Grade ≥3 toxicities (with some exceptions) ; Grade≥3 creatinine phosphokinase (CPK) with creatinine >= 1.5xbaseline; Grade 3 troponin increase with cardiac toxicity; potential Hy's Law cases; eye disorders: retinopathy or retinal detachment Grade≥3; retinal vascular disorder; Grade≥3 uveitis, blurred vision, flashing lights, floaters or others for >21 consecutive days; other Grade 4; cardiac disorders: absolute LVEF decrease >10% and the LVEF was below LLN; other Grade≥3; respiratory disorders: interstitial lung disease Grade≥2; bronchospasm Grade 3; skin and subcutaneous tissue disorders; non-adherence to treatment schedule; dose reductions. | From date of first study treatment to day 28 of study treatment (Up to 28 days) |
| Phase 2: Confirmed Objective Response (OR) Based on Investigator Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Confirmed OR, defined as a complete response (CR) or partial response (PR) per RECIST v1.1. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Both CR and PR must be confirmed by repeated assessments performed no less than 4 weeks after the criteria for response were first met. | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events During the On-Treatment Period | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. |
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Inclusion Criteria:
Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent as follows:
Have had disease progression during or following at least 1 and not more than 2 prior lines of treatment for advanced or metastatic disease.
Patients with NSCLC must have previously received treatment with an anti-PD-1 or anti-PD-L1 agent for advanced disease.
Measurable disease as per RECIST v1.1 criteria.
Provision of a baseline tumor sample.
Age ≥18 years (Japanese patients must be ≥20 years old)
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
Adequate bone marrow, renal and liver functions.
Adequate cardiac function.
Informed consent provided.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Highlands Oncology Group | Fayetteville | Arkansas | 72703 | United States | ||
| Highlands Oncology Group |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37379764 | Derived | Rodon Ahnert J, Tan DS, Garrido-Laguna I, Harb W, Bessudo A, Beck JT, Rottey S, Bahary N, Kotecki N, Zhu Z, Deng S, Kowalski K, Wei C, Pathan N, Laliberte RJ, Messersmith WA. Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial. ESMO Open. 2023 Aug;8(4):101584. doi: 10.1016/j.esmoop.2023.101584. Epub 2023 Jun 26. | |
| 32379297 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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Forty six participants were screened and 36 were enrolled, one was not treated. This study was planned to included 2 periods: phase 1b and phase 2. Due to the early termination of this study, only the doublet combinations (avelumab + binimetinib and binimetinib + talazoparib) in Phase 1b to find a safe dose were conducted, and neither the triplet combination of Phase 1b nor Phase 2 was initiated.
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| ID | Title | Description |
|---|---|---|
| FG000 | Avelumab+Binimetinib 30mg (Phase 1b) | Avelumab was administered at a fixed dose of 800 mg every 2 weeks (Q2W) in combination with binimetinib at 30 mg twice daily (BID) orally on a continuous daily dosing schedule. |
| FG001 | Avelumab+Binimetinib 45mg (Phase 1b) |
| 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 | Sep 24, 2019 | Nov 10, 2021 |
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| Binimetinib | Drug | Oral treatment |
|
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| Talazoparib | Drug | Oral treatment |
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| From the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day) assessed for a maximum duration of up to 31 months |
| Number of Participants With Hematology Laboratory Abnormalities During the On-Treatment Period Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Laboratory abnormalities were graded by NCI CTCAE version 4.03. Anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased were evaluated. This outcome measure calculated the number of participants with laboratory abnormalities whose maximum on-treatment CTCAE Grade were 1-4. | Prior to study drug administration on Days 1 and 15 of each treatment cycle, until 30 days after last dose (assessed for a maximum duration of up to 31 months) |
| Number of Participants With Chemistry Laboratory Abnormalities During the On-Treatment Period Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Laboratory abnormalities were graded by NCI CTCAE version 4.03. Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase (cpk) increased, creatinine increased, gamma-glutamyl transferase (ggt) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, serum amylase increased were evaluated. This outcome measure calculated the number of participants with laboratory abnormalities whose maximum on-treatment CTCAE Grade were 1-4. | Prior to study drug administration on Days 1 and 15 of each treatment cycle, until 30 days after last dose (assessed for a maximum duration of up to 31 months) |
| Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | Ctrough was the pre-dose concentration during multiple dosing and was directly observed from data. The lower limit of quantification (LLQ) was 0.20 microgram per milliliter. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Pre-dose on Day 1, and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12. |
| Predose Concentration During Multiple Dosing (Ctrough) for Binimetinib | Ctrough was directly observed from data. Ctrough = concentration prior to study drug administration. The LLQ was 1.00 ng/mL. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Predose on Day 15 of Cycle 1 (each cycle is 28 days), Day 1 and Day 15 of Cycle 2, Day 1 of Cycle 3 for avelumab+binimetinib groups, and on Day 8 and Day 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3 for binimetinib+talazoparib groups |
| Predose Concentration During Multiple Dosing (Ctrough) for Talazoparib | Ctrough was directly observed from data. Ctrough = concentration prior to study drug administration. The LLQ was 25 pg/mL. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Pre-dose on Days 1, 8 and Day 15 of Cycle 1 (each cycle is 28 days), and on Day 1 of Cycle 2 and Cycle 3 |
| Maximum Observed Plasma Concentration (Cmax) for Avelumab | Cmax was the maximum observed plasma concentration and was directly observed from data. The LLQ was 0.20 microgram per milliliter. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Post dose on Day 1, and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12 |
| Maximum Observed Plasma Concentration (Cmax) for Binimetinib | Cmax was the maximum observed plasma concentration and was directly observed from data. The LLQ was 1.00 ng/mL. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Post dose on Day 1 and Day 8 of Cycle 1 |
| Number of Participants With Anti-drug Antibody (ADA) Categories | Samples positive for ADA were analyzed for titer. Blood samples were collected for avelumab immunogenicity testing. Treatment-boosted ADA was defined as a positive ADA result at baseline and the titer ≥ 8×baseline titer at least once after treatment with avelumab. Treatment-induced ADA was defined as participants with ADA-negative at baseline and had at least one positive post-baseline ADA result; or if participant did not have a baseline sample, the participant had at least one positive post-baseline ADA result. | from the first dose of study up to Day 1 of Cycle 12 for a maximum of 12 months |
| Neutralizing Antibodies (nAb) Against Avelumab | The category of nAb included nAb never-positive, nAb ever-positive, baseline nAb positive, treatment-induced nAb, transient nAb response, persistent nAb response. | from the first dose of study up to Day 1 of Cycle 12 for a maximum of 12 months |
| Percentage of Participants With Confirmed Objective Response (OR) in Phase 1b Based on Investigator Assessment (RECIST v1.1) | OR is defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the 'start date' (date of first study treatment) until the date of the first documentation of progressive disease (PD). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. Clopper-Pearson method was used. | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| Progression-Free Survival (PFS) Based on Investigator Assessment (RECIST v1.1) in Phase 1b | PFS is defined as the time from the 'start date' (date of first study treatment) to the date of the first documentation of PD or death due to any cause, whichever occurs first. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. CIs were calculated using Brookmeyer and Crowley method. | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| Overall Survival (OS) in Phase 1b | OS is defined as the time from the 'start date' (date of first study treatment) to the date of death due to any cause. CIs were calculated using Brookmeyer and Crowley method. | From date of first study treatment until the date of death due to any cause (assessed for a maximum duration of up to 31 months). |
| Time-to-Tumor Response (TTR) in Phase 1b | TTR is defined, for patients with an OR, as the time from the 'start date' (date of first study treatment) to the first documentation of objective response (CR or PR) which was subsequently confirmed. OR is defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the 'start date' until the date of the first documentation of progressive disease (PD). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| Duration of Response (DR) in Phase 1b | DR is defined, for patients with OR, as the time from the first documentation of objective response (CR or PR) to the date of first documentation of PD or death due to any cause. OR is defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the 'start date' until the date of the first documentation of progressive disease (PD). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| Phase 2: Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression, DNA Damage Repair (DDR) Gene Alterations, and Tumor Mutational Burden (TMB) in Baseline Tumor Tissue. | PD-L1 expression was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. DDR gene alterations was defined as the number of somatic and germline mutations present in a panel of genes associated with DDR in baseline tumor derived nucleic acid, in germline nucleic acid and in circulating tumor DNA. TMB was defined as determination/estimation of the frequency of mutations (total and non-synonymous) present in baseline tumor derived nucleic acid samples and in baseline circulating tumor DNA. | Baseline |
| Rogers |
| Arkansas |
| 72758 |
| United States |
| Highlands Oncology Group | Springdale | Arkansas | 72762 | United States |
| California Cancer Associates for Research and Excellence, Inc (cCARE) | Encinitas | California | 92024 | United States |
| University of Colorado Denver CTO (CTRC) | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital | Aurora | Colorado | 80045 | United States |
| Horizon Oncology Research, LLC | Lafayette | Indiana | 47905 | United States |
| UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | 15232 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Utah, Huntsman Cancer Hospital | Salt Lake City | Utah | 84112 | United States |
| University of Utah, Huntsman Cancer Institute | Salt Lake City | Utah | 84112 | United States |
| Institut Jules Bordet | Brussels | 1000 | Belgium |
| UZ Gent | Ghent | 9000 | Belgium |
| Singapore National Eye Centre | Singapore | 168751 | Singapore |
| Singapore General Hospital | Singapore | 169608 | Singapore |
| SingHealth Investigational Medicine Unit | Singapore | 169608 | Singapore |
| National Heart Centre Singapore | Singapore | 169609 | Singapore |
| National Cancer Centre Singapore | Singapore | 169610 | Singapore |
| Derived |
| Sun C, Fang Y, Labrie M, Li X, Mills GB. Systems approach to rational combination therapy: PARP inhibitors. Biochem Soc Trans. 2020 Jun 30;48(3):1101-1108. doi: 10.1042/BST20191092. |
Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule. |
| FG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| FG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| Received Treatment |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Avelumab+Binimetinib 30mg (Phase 1b) | Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 30 mg BID orally on a continuous daily dosing schedule. |
| BG001 | Avelumab+Binimetinib 45mg (Phase 1b) | Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule. |
| BG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| BG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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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/Ethnicity, Customized | 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 Dose Limiting Toxicities (DLTs) During the Primary DLT Evaluation Period (Cycle 1) in Phase 1b | Any adverse events (AEs) occurring in the first cycle of treatment (28 days) which were attributable to study drugs and met DLT criteria. DLT was defined as hematologic: Grade 4 neutropenia lasting>5 days; febrile neutropenia; neutropenic infection; Grade >=3 thrombocytopenia with bleed; Grade 4 thrombocytopenia; Grade 4 anemia; non-hematologic: Grade ≥3 toxicities (with some exceptions) ; Grade≥3 creatinine phosphokinase (CPK) with creatinine >= 1.5xbaseline; Grade 3 troponin increase with cardiac toxicity; potential Hy's Law cases; eye disorders: retinopathy or retinal detachment Grade≥3; retinal vascular disorder; Grade≥3 uveitis, blurred vision, flashing lights, floaters or others for >21 consecutive days; other Grade 4; cardiac disorders: absolute LVEF decrease >10% and the LVEF was below LLN; other Grade≥3; respiratory disorders: interstitial lung disease Grade≥2; bronchospasm Grade 3; skin and subcutaneous tissue disorders; non-adherence to treatment schedule; dose reductions. | The safety analysis set included all enrolled participants who receive at least 1 dose of study treatment. The DLT-evaluable analysis set was a subset of the safety analysis set and included all enrolled participants in Phase 1b who were eligible for the study, received at least one dose of the combination treatment, and either experienced DLT during the first cycle (28 days) of treatment, or completed the DLT observation period for the first cycle of treatment without DLT. | Posted | Count of Participants | Participants | No | From date of first study treatment to day 28 of study treatment (Up to 28 days) |
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| Primary | Phase 2: Confirmed Objective Response (OR) Based on Investigator Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Confirmed OR, defined as a complete response (CR) or partial response (PR) per RECIST v1.1. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Both CR and PR must be confirmed by repeated assessments performed no less than 4 weeks after the criteria for response were first met. | Due to the early termination of this study, Phase 2 was not initiated and therefore no Phase 2 efficacy results were collected and summarized. | Posted | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
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| Secondary | Number of Participants With Adverse Events During the On-Treatment Period | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. | The safety analysis set included all enrolled participants who received at least 1 dose of study treatment. | Posted | Count of Participants | Participants | From the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day) assessed for a maximum duration of up to 31 months |
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| Secondary | Number of Participants With Hematology Laboratory Abnormalities During the On-Treatment Period Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Laboratory abnormalities were graded by NCI CTCAE version 4.03. Anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased were evaluated. This outcome measure calculated the number of participants with laboratory abnormalities whose maximum on-treatment CTCAE Grade were 1-4. | The safety analysis set included all enrolled participants who received at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Prior to study drug administration on Days 1 and 15 of each treatment cycle, until 30 days after last dose (assessed for a maximum duration of up to 31 months) |
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| Secondary | Number of Participants With Chemistry Laboratory Abnormalities During the On-Treatment Period Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Laboratory abnormalities were graded by NCI CTCAE version 4.03. Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase (cpk) increased, creatinine increased, gamma-glutamyl transferase (ggt) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, serum amylase increased were evaluated. This outcome measure calculated the number of participants with laboratory abnormalities whose maximum on-treatment CTCAE Grade were 1-4. | The safety analysis set included all enrolled participants who received at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Prior to study drug administration on Days 1 and 15 of each treatment cycle, until 30 days after last dose (assessed for a maximum duration of up to 31 months) |
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| Secondary | Predose Concentration During Multiple Dosing (Ctrough) for Avelumab | Ctrough was the pre-dose concentration during multiple dosing and was directly observed from data. The lower limit of quantification (LLQ) was 0.20 microgram per milliliter. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Number of participants analyzed: participants who had at least 1 concentration measurement for avelumab. Therefore, only 2 treatment groups including avelumab were analyzed. Number analyzed: participants who had avelumab concentrations above the LLQ at specific time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram per milliliter (ug/mL) | Pre-dose on Day 1, and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12. |
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| Secondary | Predose Concentration During Multiple Dosing (Ctrough) for Binimetinib | Ctrough was directly observed from data. Ctrough = concentration prior to study drug administration. The LLQ was 1.00 ng/mL. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Number of participants analyzed: participants who had at least 1 concentration measurement for binimetinib. Number analyzed: participants who had binimetinib concentration values above the LLQ at specific time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose on Day 15 of Cycle 1 (each cycle is 28 days), Day 1 and Day 15 of Cycle 2, Day 1 of Cycle 3 for avelumab+binimetinib groups, and on Day 8 and Day 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3 for binimetinib+talazoparib groups |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Predose Concentration During Multiple Dosing (Ctrough) for Talazoparib | Ctrough was directly observed from data. Ctrough = concentration prior to study drug administration. The LLQ was 25 pg/mL. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Number of participants analyzed: participants who had at least 1 concentration measurement for talazoparib. Therefore, only 2 treatment groups including talazoparib were analyzed. Number analyzed: participants who had talazoparib concentrations above the LLQ at specific time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | picograms per millilitre (pg/mL) | Pre-dose on Days 1, 8 and Day 15 of Cycle 1 (each cycle is 28 days), and on Day 1 of Cycle 2 and Cycle 3 |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Observed Plasma Concentration (Cmax) for Avelumab | Cmax was the maximum observed plasma concentration and was directly observed from data. The LLQ was 0.20 microgram per milliliter. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Number of participants analyzed: participants who had at least 1 concentration measurement for avelumab. Therefore, only 2 treatment groups including avelumab were analyzed. Number analyzed: participants who had avelumab concentrations above the LLQ at specific time point. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram per milliliter (ug/mL) | Post dose on Day 1, and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12 |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Observed Plasma Concentration (Cmax) for Binimetinib | Cmax was the maximum observed plasma concentration and was directly observed from data. The LLQ was 1.00 ng/mL. Concentration values below the LLQ were set to zero. Geometric Mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation is expressed in percentage. | Number of participants analyzed: participants who had at least 1 concentration measurement for binimetinib. Number analyzed: participants who had binimetinib concentrations above the LLQ at specific time point. When Cmax for binimetinib was planned to be evaluated, data collecting for Avelumab+Binimetinib cohort had already been done. Therefore, data of Cmax for binimetinib in Avelumab+Binimetinib groups hadn't been collected. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Post dose on Day 1 and Day 8 of Cycle 1 |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Anti-drug Antibody (ADA) Categories | Samples positive for ADA were analyzed for titer. Blood samples were collected for avelumab immunogenicity testing. Treatment-boosted ADA was defined as a positive ADA result at baseline and the titer ≥ 8×baseline titer at least once after treatment with avelumab. Treatment-induced ADA was defined as participants with ADA-negative at baseline and had at least one positive post-baseline ADA result; or if participant did not have a baseline sample, the participant had at least one positive post-baseline ADA result. | Participants in the safety analysis set had at least one ADA/nAb sample collected for avelumab, so only two groups (Avelumab+Binimetinib 30mg [Phase 1b] and Avelumab+Binimetinib 45mg [Phase 1b]) were analyzed. | Posted | Count of Participants | Participants | from the first dose of study up to Day 1 of Cycle 12 for a maximum of 12 months |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Neutralizing Antibodies (nAb) Against Avelumab | The category of nAb included nAb never-positive, nAb ever-positive, baseline nAb positive, treatment-induced nAb, transient nAb response, persistent nAb response. | Participants in the safety analysis set had at least one ADA/nAb sample collected for avelumab. Due to the low observed immunogenicity rate, nAb analysis was not conducted. | Posted | from the first dose of study up to Day 1 of Cycle 12 for a maximum of 12 months |
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Confirmed Objective Response (OR) in Phase 1b Based on Investigator Assessment (RECIST v1.1) | OR is defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the 'start date' (date of first study treatment) until the date of the first documentation of progressive disease (PD). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. Clopper-Pearson method was used. | The full analysis set included all enrolled participants who received at least 1 dose of study treatment. | Posted | Number | 95% Confidence Interval | Percentage of participants | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival (PFS) Based on Investigator Assessment (RECIST v1.1) in Phase 1b | PFS is defined as the time from the 'start date' (date of first study treatment) to the date of the first documentation of PD or death due to any cause, whichever occurs first. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. CIs were calculated using Brookmeyer and Crowley method. | The full analysis set included all enrolled participants who received at least 1 dose of study treatment. | Posted | Median | 95% Confidence Interval | months | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) in Phase 1b | OS is defined as the time from the 'start date' (date of first study treatment) to the date of death due to any cause. CIs were calculated using Brookmeyer and Crowley method. | The full analysis set included all enrolled participants who received at least 1 dose of study treatment. | Posted | Median | 95% Confidence Interval | months | From date of first study treatment until the date of death due to any cause (assessed for a maximum duration of up to 31 months). |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Time-to-Tumor Response (TTR) in Phase 1b | TTR is defined, for patients with an OR, as the time from the 'start date' (date of first study treatment) to the first documentation of objective response (CR or PR) which was subsequently confirmed. OR is defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the 'start date' until the date of the first documentation of progressive disease (PD). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. | The full analysis set included all enrolled participants who received at least 1 dose of study treatment and achieved objective response: only 1 participant in the Avelumab+Binimetinib 45mg (Phase 1b) group achieved OR. The summary of this endpoint cannot be estimated due to small sample size (1 participant). | Posted | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response (DR) in Phase 1b | DR is defined, for patients with OR, as the time from the first documentation of objective response (CR or PR) to the date of first documentation of PD or death due to any cause. OR is defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the 'start date' until the date of the first documentation of progressive disease (PD). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. | The full analysis set included all enrolled participants who received at least 1 dose of study treatment and achieved objective response: only 1 participant in the Avelumab+Binimetinib 45mg (Phase 1b) group achieved OR. The summary of this endpoint cannot be estimated due to small sample size (1 participant). | Posted | From date of first study treatment until the date of first documentation of progressive disease or death due to any cause (assessed for a maximum duration of up to 31 months). |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Phase 2: Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression, DNA Damage Repair (DDR) Gene Alterations, and Tumor Mutational Burden (TMB) in Baseline Tumor Tissue. | PD-L1 expression was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. DDR gene alterations was defined as the number of somatic and germline mutations present in a panel of genes associated with DDR in baseline tumor derived nucleic acid, in germline nucleic acid and in circulating tumor DNA. TMB was defined as determination/estimation of the frequency of mutations (total and non-synonymous) present in baseline tumor derived nucleic acid samples and in baseline circulating tumor DNA. | The biomarkers were for the phase 2 part. since phase 2 was not initiated, the results was not provided. | Posted | Baseline |
|
|
From the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day) assessed for a maximum duration of up to 31 months
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 | Avelumab+Binimetinib 30mg (Phase 1b) | Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 30 mg BID orally on a continuous daily dosing schedule. | 9 | 10 | 6 | 10 | 10 | 10 |
| EG001 | Avelumab+Binimetinib 45mg (Phase 1b) | Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule. | 9 | 12 | 9 | 12 | 12 | 12 |
| EG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. | 5 | 7 | 3 | 7 | 7 | 7 |
| EG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. | 3 | 6 | 3 | 6 | 6 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Systemic inflammatory response syndrome | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.1 | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Detachment of retinal pigment epithelium | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Glaucoma | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Macular oedema | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Photopsia | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Retinopathy | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Subretinal fluid | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Cheilitis | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Lip blister | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Obstruction gastric | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Nail infection | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Animal bite | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
| |
| Eye contusion | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
| |
| Skin wound | Injury, poisoning and procedural complications | MedDRA v23.1 | Non-systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Ammonia increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Fibrin D dimer increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Troponin T increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Burning sensation | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Tension headache | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Diastolic hypertension | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v23.1 | Non-systematic Assessment |
|
Because there was a low probability of technical success for achieving target dose levels of the triplet combination while maintaining acceptable tolerability, and only limited anti-tumor activity was observed in this study of participants with mPDAC, a decision on the early termination was made on 14 December 2020. Phase 2 was not initiated, so PD-L1 Expression, DDR Gene Alterations, TMB and OR were not analyzed. Due to the low observed immunogenicity rate, nAb analysis was not conducted.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 13, 2019 | Nov 10, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000609138 | avelumab |
| C581313 | binimetinib |
| C586365 | talazoparib |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| White |
|
| Not Reported |
|
| OG001 |
| Avelumab+Binimetinib 45mg (Phase 1b) |
Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule. |
| OG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
| Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) |
Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule.
| OG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
|
|
| OG002 |
| Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) |
Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG002 |
| Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) |
Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule. |
| OG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
| OG003 |
| Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) |
Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
|
| Avelumab+Binimetinib 45mg (Phase 1b) |
Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule. |
| OG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
|
Avelumab was administered at a fixed dose of 800 mg Q2W in combination with binimetinib at 45 mg BID orally on a continuous daily dosing schedule. |
| OG002 | Binimetinib 30mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 30 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
| OG003 | Binimetinib 45mg+Talazoparib 0.75mg (Phase 1b) | Binimetinib 45 mg was administered orally BID (7 days on / 7 days off) with talazoparib at 0.75 mg once daily (QD) orally on a continuous dosing schedule. |
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