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Study was terminated by sponsor after Phase 1b as pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort.
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This study will evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of revumenib in participants with colorectal cancer (CRC) or other solid tumors who have failed at least 1 prior line of therapy.
The study will be conducted in two parts. The Phase 1 portion of the study consists of a dose escalation cohort, and a signal-seeking expansion where anti-tumor activity signals will be evaluated. The Phase 2 portion of the study will further confirm the anti-tumor activity signals of revumenib.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1a: Dose Escalation | Experimental | Participants will receive revumenib tablets or capsules three times a day (TID) or two times a day (BID) from Day 1 of each 28-day cycle. |
|
| Phase 1b: Signal-Seeking | Experimental | Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle. |
|
| Phase 2: Revumenib | Experimental | Participants will receive revumenib tablets TID or BID from Day 1 of each 28-day cycle. |
|
| Phase 2: Chemotherapy | Active Comparator | Participants will receive chemotherapy from Day 1 of each 28-day cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Revumenib | Drug | Revumenib administered orally with or without food. Participants may continue to receive treatment until disease progression or until they experience unacceptable toxicity. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | DLT was defined as any of the following occurring in Cycle 1: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) unresolved to Grade 2 (ANC >1500 cells/mm^3) or baseline for more than 7 consecutive days in the absence of growth factor support, ≥Grade 3 neutropenia (ANC <1000 cells/mm^3) with a single temperature of >38.3°Celsius (101°Fahrenheit) or a sustained temperature of ≥38°Celsius (100.4°Fahrenheit) for more than 1 hour, Grade 4 thrombocytopenia (<25,000/mm^3) of any duration, ≥Grade 3 thrombocytopenia (<50,000/mm^3) with clinically significant bleeding, Grade 4 anemia (i.e, life-threatening consequences; urgent intervention indicated) or ≥Grade 3 nonhematologic toxicity as defined in Common Terminology Criteria for Adverse Events version 5.0 scale where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=Life-threatening and 5=Death. | Day 1 up to Day 28 |
| Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention, whether or not considered related to the study intervention. TEAEs were defined as those having an onset on or after the first dose of revumenib or a sign, symptom, or a diagnosis that worsened on or after first dose of revumenib but no later than 30 days after the date of the last dose of revumenib. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Up to 2.2 years |
| Phase 1: Disease Control Rate (DCR) | DCR was defined as the percentage of participants with objective evidence of confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) according to Response Evaluation in Solid Tumors (RECIST) version 1.1 criteria as assessed by the investigator. CR=disappearance of all target lesions; disappearance of non-target lesions. PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1a: Maximum Plasma Concentration (Cmax) of Revumenib | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days) | |
| Phase 1b: Maximum Plasma Concentration (Cmax) of Revumenib | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Honor Health Research Institute | Scottsdale | Arizona | 85258 | United States | ||
| Massachusetts General Hospital |
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The study consisted of Phase 1 and Phase 2. Phase 1 portion of study consisted of a Phase 1a, dose escalation, and a Phase 1b, signal-seeking expansion in colorectal carcinoma. No participants were enrolled in Phase 2 because pre-defined signals of efficacy were not met in Phase 1b dose expansion cohort. So, study was terminated by sponsor after Phase 1b. Data were collected and reported by treatment arm instead of dose received in Phase 1. No participants rolled over from Phase 1a to Phase 1b.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1a: Revumenib 160 mg Tablet or 163 mg Capsule | Participants received revumenib 160 milligrams (mg) tablets or 163 mg capsules orally three times a day (TID) or two times a day (BID) from Day 1 of each 28-day cycle. |
| FG001 | Phase 1a: Revumenib 220 mg Tablet or 226 mg Capsule | Participants received revumenib 220 mg tablets or 226 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
| FG002 | Phase 1a: Revumenib 270 mg Tablet or 276 mg Capsule | Participants received revumenib 270 mg tablets or 276 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
| FG003 | Phase 1b: Revumenib 270 mg Tablet | Participants received revumenib 270 mg tablets orally TID or BID from Day 1 of each 28-day cycle. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population consisted of all enrolled participants who received at least 1 dose of study treatment during the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1a: Revumenib 160 mg Tablet or 163 mg Capsule | Participants received Revumenib 160 mg tablets or 163 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
| BG001 | Phase 1a: Revumenib 220 mg Tablet or 226 mg Capsule |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Phase 1a: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | DLT was defined as any of the following occurring in Cycle 1: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) unresolved to Grade 2 (ANC >1500 cells/mm^3) or baseline for more than 7 consecutive days in the absence of growth factor support, ≥Grade 3 neutropenia (ANC <1000 cells/mm^3) with a single temperature of >38.3°Celsius (101°Fahrenheit) or a sustained temperature of ≥38°Celsius (100.4°Fahrenheit) for more than 1 hour, Grade 4 thrombocytopenia (<25,000/mm^3) of any duration, ≥Grade 3 thrombocytopenia (<50,000/mm^3) with clinically significant bleeding, Grade 4 anemia (i.e, life-threatening consequences; urgent intervention indicated) or ≥Grade 3 nonhematologic toxicity as defined in Common Terminology Criteria for Adverse Events version 5.0 scale where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=Life-threatening and 5=Death. | DLT-evaluable population included all participants with data used for implementing the dose escalation schedule (Phase 1a). | Posted | Count of Participants | Participants | Day 1 up to Day 28 |
Up to 2.2 years
Safety population consisted of all enrolled participants who received at least 1 dose of study treatment during the study. Safety data were collected and reported by treatment arm instead of dose received in Phase 1.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1a: Revumenib 160 mg Tablet or 163 mg Capsule | Participants received Revumenib 160 mg tablets or 163 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Syndax Pharmaceuticals | 781-419-1400 | clinicaltrials@syndax.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 18, 2024 | Jun 5, 2026 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 21, 2025 | Jun 5, 2026 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C000728983 | revumenib |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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Phase 1a dose escalation portion of the study will employ a Rolling 6 trial design, followed by a Phase 1b signal-seeking portion, and a Phase 2 randomized (2:1) signal confirmation portion.
Phase 1: Non-randomized; Phase 2: Randomized
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|
| Chemotherapy | Drug | Either Lonsurf® or Stivarga® administered per the investigator's choice at the respective drug label's dose and schedule. Participants may continue to receive treatment until disease progression or until they experience unacceptable toxicity. |
|
| Up to 2.2 years |
| Phase 1: Overall Response Rate (ORR) | ORR was defined as the percentage of participants who achieved a best overall response of PR or CR according to RECIST v1.1 criteria as assessed by the investigator. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. | Up to 2.2 years |
| Phase 2: Progression Free Survival (PFS) | PFS was defined as the time from the first dosing date to the first documented progression or death due to any cause, whichever occurred first. | Up to 2.2 years |
| Phase 1a: Area Under the Plasma Concentration Versus Time Curve (AUC0-t) of Revumenib | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days) |
| Phase 1a: Time to Maximum Plasma Concentration (Tmax) of Revumenib | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days) |
| Phase 1b: Time to Maximum Plasma Concentration (Tmax) of Revumenib | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days) |
| Phase 1b: Area Under the Plasma Concentration Versus Time Curve (AUC0-t) of Revumenib | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days) |
| Phase 2: Area Under The Concentration Time Curve of Revumenib | Up to 2.2 years |
| Phase 2: Maximum Plasma Concentration (Cmax) of Revumenib | Up to 2.2 years |
| Phase 2: Time to Maximum Plasma Concentration (Tmax) of Revumenib | Up to 2.2 years |
| Phase 2: Number of Participants With TEAEs | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention, whether or not considered related to the study intervention. TEAEs were defined as those having an onset on or after the first dose of revumenib or a sign, symptom, or a diagnosis that worsened on or after first dose of revumenib but no later than 30 days after the date of the last dose of revumenib. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Up to 2.2 years |
| Phase 2: Overall Survival (OS) | OS was defined as the time from the date of first dosing of revumenib to death due to any cause. | Up to 2.2 years |
| Phase 2: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review | DCR was defined as the percentage of participants with objective evidence of confirmed CR, confirmed PR, or SD according to RECIST version 1.1 criteria as assessed by blinded radiographic review. CR=disappearance of all target lesions; disappearance of non-target lesions. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | Up to 2.2 years |
| Phase 2: ORR as Assessed by Blinded Radiographic Review | ORR was defined as the percentage of participants who achieved a best overall response of PR or CR according to RECIST v1.1 criteria as assessed by blinded radiographic review. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. | Up to 2.2 years |
| Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review | DOR was defined as the time from the first documented response (CR or PR) to the first documented objective PD or death due to any case according to RECIST v1.1 criteria as assessed by blinded radiographic review. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | Up to 2.2 years |
| Phase 2: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles) as Assessed by the Investigator | DCR was defined as the percentage of participants with objective evidence of confirmed CR, confirmed PR, or SD according to RECIST version 1.1 criteria as assessed by investigator. CR=disappearance of all target lesions; disappearance of non-target lesions. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | Up to 2.2 years |
| Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator | ORR was defined as the percentage of participants who achieved a best overall response of PR or CR according to RECIST v1.1 criteria as assessed by investigator. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. | Up to 2.2 years |
| Phase 2: DOR as Assessed by the Investigator | DOR was defined as the time from the first documented response (CR or PR) to the first documented objective PD or death due to any case according to RECIST v1.1 criteria as assessed by investigator. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | Up to 2.2 years |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Memorial Sloan Kettering Cancer Center | Manhattan | New York | 10065 | United States |
| Gabrail Cancer Center | Canton | Ohio | 44718 | United States |
| Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| Inova Schar Cancer Institute | Fairfax | Virginia | 22031 | United States |
| Withdrawal by Subject |
|
| Study terminated by sponsor |
|
Participants received Revumenib 220 mg tablets or 226 mg capsules orally TID or BID from Day 1 of each 28-day cycle.
| BG002 | Phase 1a: Revumenib 270 mg Tablet or 276 mg Capsule | Participants received Revumenib 270 mg tablets or 276 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
| BG003 | Phase 1b: Revumenib 270 mg Tablet | Participants received Revumenib 270 mg tablets orally TID or BID from Day 1 of each 28-day cycle. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Phase 1a: Revumenib 160 mg Tablet or 163 mg Capsule | Participants received Revumenib 160 mg tablets or 163 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
| OG001 | Phase 1a: Revumenib 220 mg Tablet or 226 mg Capsule | Participants received Revumenib 220 mg tablets or 226 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
| OG002 | Phase 1a: Revumenib 270 mg Tablet or 276 mg Capsule | Participants received Revumenib 270 mg tablets or 276 mg capsules orally TID or BID from Day 1 of each 28-day cycle. |
|
|
| Primary | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention, whether or not considered related to the study intervention. TEAEs were defined as those having an onset on or after the first dose of revumenib or a sign, symptom, or a diagnosis that worsened on or after first dose of revumenib but no later than 30 days after the date of the last dose of revumenib. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Safety population consisted of all enrolled participants who received at least 1 dose of study treatment during the study. | Posted | Count of Participants | Participants | Up to 2.2 years |
|
|
|
| Primary | Phase 1: Disease Control Rate (DCR) | DCR was defined as the percentage of participants with objective evidence of confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) according to Response Evaluation in Solid Tumors (RECIST) version 1.1 criteria as assessed by the investigator. CR=disappearance of all target lesions; disappearance of non-target lesions. PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | Response evaluable population included all treated participants who had at least 1 post-baseline disease assessment or discontinued treatment due to clinical disease progression. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 2.2 years |
|
|
|
| Primary | Phase 1: Overall Response Rate (ORR) | ORR was defined as the percentage of participants who achieved a best overall response of PR or CR according to RECIST v1.1 criteria as assessed by the investigator. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. | Response evaluable population included all treated participants who had at least 1 post-baseline disease assessment or discontinued treatment due to clinical disease progression. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 2.2 years |
|
|
|
| Primary | Phase 2: Progression Free Survival (PFS) | PFS was defined as the time from the first dosing date to the first documented progression or death due to any cause, whichever occurred first. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 1a: Maximum Plasma Concentration (Cmax) of Revumenib | Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of revumenib and for whom at least 1 valid plasma concentration of revumenib was determined. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days) |
|
|
|
| Secondary | Phase 1b: Maximum Plasma Concentration (Cmax) of Revumenib | PK analysis set included all participants who received at least 1 dose of revumenib and for whom at least 1 valid plasma concentration of revumenib was determined. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days) |
|
|
|
| Secondary | Phase 1a: Area Under the Plasma Concentration Versus Time Curve (AUC0-t) of Revumenib | PK analysis set included all participants who received at least 1 dose of revumenib and for whom at least 1 valid plasma concentration of revumenib was determined. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*nanograms/milliliter | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days) |
|
|
|
| Secondary | Phase 1a: Time to Maximum Plasma Concentration (Tmax) of Revumenib | PK analysis set included all participants who received at least 1 dose of revumenib and for whom at least 1 valid plasma concentration of revumenib was determined. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points. | Posted | Median | Full Range | hours | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15, Cycle 5 Day 1 (Cycle length=28 days) |
|
|
|
| Secondary | Phase 1b: Time to Maximum Plasma Concentration (Tmax) of Revumenib | PK analysis set included all participants who received at least 1 dose of revumenib and for whom at least 1 valid plasma concentration of revumenib was determined. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points. | Posted | Median | Full Range | hours | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days) |
|
|
|
| Secondary | Phase 1b: Area Under the Plasma Concentration Versus Time Curve (AUC0-t) of Revumenib | PK analysis set included all participants who received at least 1 dose of revumenib and for whom at least 1 valid plasma concentration of revumenib was determined. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 1 Day 7, Cycle 1 Day 14, Cycle 2 Day 8, Cycle 2 Day 15 (Cycle length=28 days) |
|
|
|
| Secondary | Phase 2: Area Under The Concentration Time Curve of Revumenib | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Maximum Plasma Concentration (Cmax) of Revumenib | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Time to Maximum Plasma Concentration (Tmax) of Revumenib | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Number of Participants With TEAEs | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention, whether or not considered related to the study intervention. TEAEs were defined as those having an onset on or after the first dose of revumenib or a sign, symptom, or a diagnosis that worsened on or after first dose of revumenib but no later than 30 days after the date of the last dose of revumenib. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Overall Survival (OS) | OS was defined as the time from the date of first dosing of revumenib to death due to any cause. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles) as Assessed by Blinded Radiographic Review | DCR was defined as the percentage of participants with objective evidence of confirmed CR, confirmed PR, or SD according to RECIST version 1.1 criteria as assessed by blinded radiographic review. CR=disappearance of all target lesions; disappearance of non-target lesions. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: ORR as Assessed by Blinded Radiographic Review | ORR was defined as the percentage of participants who achieved a best overall response of PR or CR according to RECIST v1.1 criteria as assessed by blinded radiographic review. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Duration of Response (DOR) as Assessed by Blinded Radiographic Review | DOR was defined as the time from the first documented response (CR or PR) to the first documented objective PD or death due to any case according to RECIST v1.1 criteria as assessed by blinded radiographic review. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Disease Control Rate (DCR) at 6 Cycles (28-Day Cycles) as Assessed by the Investigator | DCR was defined as the percentage of participants with objective evidence of confirmed CR, confirmed PR, or SD according to RECIST version 1.1 criteria as assessed by investigator. CR=disappearance of all target lesions; disappearance of non-target lesions. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator | ORR was defined as the percentage of participants who achieved a best overall response of PR or CR according to RECIST v1.1 criteria as assessed by investigator. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| Secondary | Phase 2: DOR as Assessed by the Investigator | DOR was defined as the time from the first documented response (CR or PR) to the first documented objective PD or death due to any case according to RECIST v1.1 criteria as assessed by investigator. PR=At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. CR=Disappearance of all target lesions; disappearance of all nontarget lesions. PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. | No participants were enrolled in Phase 2 because the pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. So, the study was terminated by the sponsor after Phase 1b. | Posted | Up to 2.2 years |
|
|
| 3 |
| 3 |
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Phase 1a: Revumenib 220 mg Tablet or 226 mg Capsule | Participants received Revumenib 220 mg tablets or 226 mg capsules orally TID or BID from Day 1 of each 28-day cycle. | 8 | 10 | 2 | 10 | 8 | 10 |
| EG002 | Phase 1a: Revumenib 270 mg Tablet or 276 mg Capsule | Participants received Revumenib 270 mg tablets or 276 mg capsules orally TID or BID from Day 1 of each 28-day cycle. | 5 | 6 | 2 | 6 | 6 | 6 |
| EG003 | Phase 1b: Revumenib 270 mg Tablet | Participants received Revumenib 270 mg tablets orally TID or BID from Day 1 of each 28-day cycle. | 15 | 22 | 6 | 22 | 22 | 22 |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Abdominal infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Biliary sepsis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Biliary tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Anal incontinence | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Retching | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Mallory-Weiss syndrome | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Oral dysaesthesia | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Electrocardiogram abnormal | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Enterobacter infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pulmonary pain | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Renal vein thrombosis | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
|
| Stoma site haemorrhage | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
|
| Flat affect | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 26.0 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 26.0 | Systematic Assessment |
|
Publication of the results of the multi-center Study shall not be made before the first multi-site publication by Sponsor or Publications Committee. No Public Presentation by Institution or Investigator will be made until Study Documentation/Results from all sites are received and analyzed by Sponsor. Separate publication by Investigator will be delayed for a specified period time until the initial publication by Committee or Sponsor, or a determination is made not to make such publication.
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| Cycle 1 Day 14 |
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| Cycle 2 Day 8 |
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| Cycle 2 Day 15 |
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| Cycle 5 Day 1 |
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| Cycle 2 Day 8 |
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| Cycle 2 Day 15 |
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| Cycle 1 Day 14 |
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| Cycle 2 Day 8 |
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| Cycle 2 Day 15 |
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| Cycle 5 Day 1 |
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| Cycle 1 Day 14 |
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| Cycle 2 Day 8 |
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| Cycle 2 Day 15 |
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| Cycle 5 Day 1 |
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| Cycle 2 Day 8 |
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| Cycle 2 Day 15 |
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| Cycle 2 Day 8 |
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| Cycle 2 Day 15 |
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