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The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns
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An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 in advanced or metastatic solid tumors with IDH mutation.
HMPL-306 is a dual IDH1/2 inhibitor
This is a phase 1, open-label, multicenter study to evaluate the safety and tolerability of HMPL-306 administered orally in the treatment of subjects with advanced or metastatic solid tumors with IDH mutation. The study consists of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). The dose escalation part will determine the MTD/RP2D. The dose expansion part will administer the MTD/RP2D to mIDH-positive solid tumor malignancies including, but not limited to, cholangiocarcinoma, skeletal chondrosarcoma, low-grade glioma, perioperative low-grade glioma
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 Dose Escalation Cohorts | Experimental | Patients from each cohort will be administered HMPL-306 orally QD |
|
| Part 2 Dose Expansion Cohorts | Experimental | Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HMPL-306 | Drug | Administered orally QD in a 28-day continuous dosing treatment cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Recommended Phase 2 Dose (RP2D) of HMPL-306 | RP2D determination took the following criteria under consideration: determination of maximum tolerated dose (MTD) achieved during the dose escalation part and assessment of safety, pharmacokinetics (PK) and pharmacodynamics (PD). The modified toxicity probability interval-2 design was used to perform dose escalation and planned to determine MTD/RP2D. | From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 |
| Part 1: Number of Patients With Dose-limiting Toxicities (DLTs) | DLT:occurrence of any of following treatment-emergent adverse events (TEAEs) during DLT assessment window unless clearly unrelated to study drug/judged by investigator as not clinically significant:
| From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 |
| Parts 1 and 2: Number of Patients With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs) | AE:unfavorable,unintended sign,symptom or disease temporally associated with use of study drug or other protocol-imposed drug, whether or not considered drug related. SAE:AE that resulted in death, was life threatening, inpatient hospitalization/prolongation of existing hospitalization, persistent/significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, important medical event that jeopardized patient and required medical/surgical intervention to prevent above outcome or signs, symptoms or clinical sequelae of suspected overdose of either study drug or a concomitant medication. TEAE:AE with onset on/after start of study drug until 30 days after last dose or prior to start of subsequent anti-tumor therapy, or AE with onset before start of study drug but worsened in severity after study drug administration or beyond 30 days after last dose or after start of subsequent anti-tumor therapy and treatment-related SAEs. |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 and 2: Objective Response Rate (ORR) | ORR by response evaluation criteria in solid tumors (RECIST) v1.1 was defined as the percentage of patients with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. ORR by response assessment in neuro-oncology criteria (RANO) was defined as the percentage of patients with a BOR of CR or PR or minor response (MR) as determined by the investigator using RANO criteria mentioned in protocol for glioma patients. |
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Key Inclusion Criteria:
Subjects are eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
Key Exclusion Criteria:
Subjects are not eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
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| Name | Affiliation | Role |
|---|---|---|
| Bo Zhang | Hutchison Medipharma Limited | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarcoma Oncology Research Center | Santa Monica | California | 90403 | United States | ||
| Emory University |
The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns. At the time of study termination, patients had not entered the dose expansion part (Part 2) of the study (it was never initiated). 42 patients were enrolled in the dose escalation part.
This Phase 1, open-label study was conducted in patients with locally advanced or metastatic solid tumors with isocitrate dehydrogenase (IDH) mutations and consisted of dose escalation part (Part 1) and dose expansion part (Part 2).
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Cohort-1: HMPL-306 50 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 50 milligrams (mg) tablet orally once daily (QD) in a 28-day continuous dosing treatment cycle until disease progression (Pd), initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| FG001 | Part 1: Cohort-2: HMPL-306 100 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 100 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| FG002 | Part 1: Cohort-3: HMPL-306 150 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 150 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| FG003 | Part 1: Cohort-4: HMPL-306 200 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 200 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| FG004 | Part 1: Cohort-5: HMPL-306 250 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 250 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| FG005 | Part 1: Cohort-6: HMPL-306 300 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 300 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| FG006 | Part 1: Cohort-7: HMPL-306 350 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 350 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| FG007 | Part 1: Cohort-8: HMPL-306 400 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 400 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety analysis set included all enrolled patients who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Cohort-1: HMPL-306 50 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 50 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| 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 | Part 1: Recommended Phase 2 Dose (RP2D) of HMPL-306 | RP2D determination took the following criteria under consideration: determination of maximum tolerated dose (MTD) achieved during the dose escalation part and assessment of safety, pharmacokinetics (PK) and pharmacodynamics (PD). The modified toxicity probability interval-2 design was used to perform dose escalation and planned to determine MTD/RP2D. | The safety analysis set included all enrolled patients who received at least 1 dose of study drug. | Posted | Number | milligrams | From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 |
|
Adverse events were collected from the from the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 43 months for Part 1. All-cause mortality (deaths) was collected from the first dose of study drug (Day 1) up to end of follow-up, approximately 47 months.
The safety analysis set included all enrolled patients who received at least 1 dose of study drug. Due to early study termination, Part 2 was never initiated.
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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 | Part 1: Cohort-1: HMPL-306 50 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 50 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bacteraemia | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wade Clutson | HUTCHMED Limited | 973-306-4490 | HMPL306@hutch-med.com |
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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 | May 17, 2022 | Dec 11, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 12, 2025 | Dec 3, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D018281 | Cholangiocarcinoma |
| D005910 | Glioma |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 43 months for Part 1 |
| Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
| Parts 1 and 2: Disease Control Rate (DCR) | DCR by RECIST v1.1 was defined as percentage of patients with BOR of CR, PR, or stable disease (SD) lasting at least 7 weeks as determined by investigator.CR: disappearance of all target lesions.PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameters.SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Pd, taking as reference the smallest sum on study. Pd: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (nadir), including baseline. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. DCR by RANO was defined as percentage of patients with BOR of CR, PR, MR, or SD lasting at least 7 weeks as determined by investigator using RANO criteria mentioned in protocol for glioma patients. | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
| Parts 1 and 2: Duration of Response (DoR) | DoR by RECIST v1.1 was defined as the time from the first occurrence of confirmed PR or confirmed CR until Pd or death, whichever came first. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Pd: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. DoR by RANO was defined as the time from the first occurrence of CR or PR or MR using RANO criteria mentioned in protocol for glioma patients, until disease progression or death, whichever comes first. Due to early study termination, Part 2 was never initiated. | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
| Parts 1 and 2: Time to Response (TTR) | TTR by RECIST v1.1 was defined as the time from start of study treatment until the date of first documented objective response, either confirmed CR or confirmed PR (whichever status was recorded first). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. TTR by RANO was defined as the time from start of study treatment until the date of first documented objective response, either CR or PR or MR (whichever status was recorded first) using RANO criteria mentioned in protocol for glioma patients. Due to early study termination, Part 2 was never initiated. | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
| Parts 1 and 2: Progression-free Survival (PFS) | PFS was defined as the time from the date of first administration of study drug until the first radiographic documentation of objective progression as assessed by investigator using RECIST v1.1 or RANO criteria for glioma patients, or death from any cause. As per RECIST v1.1: Pd: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression. Criteria for RANO as mentioned in protocol. | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
| Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of HMPL-306 | Blood samples were collected at the specified timepoints to determine Cmax of HMPL-306. | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1 |
| Parts 1 and 2: Time to Peak Plasma Concentration (Tmax) of HMPL-306 | Blood samples were collected at the specified timepoints to determine Tmax of HMPL-306. | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1 |
| Parts 1 and 2: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of HMPL-306 | Blood samples were collected at the specified timepoints to determine AUC0-24 of HMPL-306. | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1 |
| Parts 1 and 2: Maximum Inhibition Rate of Plasma 2-Hydroxyglutaric Acid (2-HG) | Blood samples were collected at the specified timepoints to determine plasma concentrations of 2-HG which was a PD marker. The maximum inhibition rate of 2-HG for patients in different dose groups is presented. | From screening (Day -28) until end of treatment, approximately 42 months for Part 1 |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| UPMC Hillman Cancer | Pittsburgh | Pennsylvania | 15232 | United States |
| Houston Methodist | Houston | Texas | 77030 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Hospital de la Santa creu i Sant Pau | Barcelona | 08025 | Spain |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| Withdrawal by Subject |
|
| Death |
|
| BG001 |
| Part 1: Cohort-2: HMPL-306 100 mg |
Patients with locally advanced or metastatic solid tumors received HMPL-306 100 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| BG002 | Part 1: Cohort-3: HMPL-306 150 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 150 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| BG003 | Part 1: Cohort-4: HMPL-306 200 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 200 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| BG004 | Part 1: Cohort-5: HMPL-306 250 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 250 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| BG005 | Part 1: Cohort-6: HMPL-306 300 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 300 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| BG006 | Part 1: Cohort-7: HMPL-306 350 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 350 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| BG007 | Part 1: Cohort-8: HMPL-306 400 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 400 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. |
| BG008 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Part 1: Number of Patients With Dose-limiting Toxicities (DLTs) | DLT:occurrence of any of following treatment-emergent adverse events (TEAEs) during DLT assessment window unless clearly unrelated to study drug/judged by investigator as not clinically significant:
| Analysis was performed on the DLT-evaluable analysis set for all patients enrolled in Part 1 of the study. A patient was DLT-evaluable if met the following criteria: had received at least 75% of the assigned dose of study drug during the DLT assessment window or had not completed DLT assessment period due to a DLT. | Posted | Count of Participants | Participants | No | From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 |
|
|
|
| Primary | Parts 1 and 2: Number of Patients With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs) | AE:unfavorable,unintended sign,symptom or disease temporally associated with use of study drug or other protocol-imposed drug, whether or not considered drug related. SAE:AE that resulted in death, was life threatening, inpatient hospitalization/prolongation of existing hospitalization, persistent/significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, important medical event that jeopardized patient and required medical/surgical intervention to prevent above outcome or signs, symptoms or clinical sequelae of suspected overdose of either study drug or a concomitant medication. TEAE:AE with onset on/after start of study drug until 30 days after last dose or prior to start of subsequent anti-tumor therapy, or AE with onset before start of study drug but worsened in severity after study drug administration or beyond 30 days after last dose or after start of subsequent anti-tumor therapy and treatment-related SAEs. | The safety analysis set included all enrolled patients who received at least 1 dose of study drug. Due to early study termination, Part 2 was never initiated. | Posted | Count of Participants | Participants | No | From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 43 months for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Objective Response Rate (ORR) | ORR by response evaluation criteria in solid tumors (RECIST) v1.1 was defined as the percentage of patients with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. ORR by response assessment in neuro-oncology criteria (RANO) was defined as the percentage of patients with a BOR of CR or PR or minor response (MR) as determined by the investigator using RANO criteria mentioned in protocol for glioma patients. | The response evaluable analysis set included all patients who were in the safety analysis set and had a measurable lesion at the baseline tumor assessment, and either (i) had at least 1 post-dose tumor assessment, or (ii) did not have post-dose tumor assessment but had clinical progression as noted by the investigator, or died before their first post-dose tumor scan. Due to early study termination, Part 2 was never initiated. | Posted | Number | 95% Confidence Interval | percentage of patients | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Disease Control Rate (DCR) | DCR by RECIST v1.1 was defined as percentage of patients with BOR of CR, PR, or stable disease (SD) lasting at least 7 weeks as determined by investigator.CR: disappearance of all target lesions.PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameters.SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Pd, taking as reference the smallest sum on study. Pd: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (nadir), including baseline. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. DCR by RANO was defined as percentage of patients with BOR of CR, PR, MR, or SD lasting at least 7 weeks as determined by investigator using RANO criteria mentioned in protocol for glioma patients. | The response evaluable analysis set included all patients who were in the safety analysis set and had a measurable lesion at the baseline tumor assessment, and either (i) had at least 1 post-dose tumor assessment, or (ii) did not have post-dose tumor assessment but had clinical progression as noted by the investigator, or died before their first post-dose tumor scan. Due to early study termination, Part 2 was never initiated. | Posted | Number | 95% Confidence Interval | percentage of patients | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Duration of Response (DoR) | DoR by RECIST v1.1 was defined as the time from the first occurrence of confirmed PR or confirmed CR until Pd or death, whichever came first. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Pd: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. DoR by RANO was defined as the time from the first occurrence of CR or PR or MR using RANO criteria mentioned in protocol for glioma patients, until disease progression or death, whichever comes first. Due to early study termination, Part 2 was never initiated. | The response evaluable analysis set included all patients who were in the safety analysis set and had a measurable lesion at the baseline tumor assessment, and either (i) had at least 1 post-dose tumor assessment, or (ii) did not have post-dose tumor assessment but had clinical progression as noted by the investigator, or died before their first post-dose tumor scan. Only those patients with objective responses of confirmed CR or confirmed PR were included in this analysis. | Posted | Median | 95% Confidence Interval | months | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Time to Response (TTR) | TTR by RECIST v1.1 was defined as the time from start of study treatment until the date of first documented objective response, either confirmed CR or confirmed PR (whichever status was recorded first). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. TTR by RANO was defined as the time from start of study treatment until the date of first documented objective response, either CR or PR or MR (whichever status was recorded first) using RANO criteria mentioned in protocol for glioma patients. Due to early study termination, Part 2 was never initiated. | The response evaluable analysis set included all patients who were in the safety analysis set and had a measurable lesion at the baseline tumor assessment, and either (i) had at least 1 post-dose tumor assessment, or (ii) did not have post-dose tumor assessment but had clinical progression as noted by the investigator, or died before their first post-dose tumor scan. Only those patients whose BOR was either confirmed CR or confirmed PR were included in this analysis. | Posted | Median | 95% Confidence Interval | months | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Progression-free Survival (PFS) | PFS was defined as the time from the date of first administration of study drug until the first radiographic documentation of objective progression as assessed by investigator using RECIST v1.1 or RANO criteria for glioma patients, or death from any cause. As per RECIST v1.1: Pd: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression. Criteria for RANO as mentioned in protocol. | The safety analysis set included all enrolled patients who received at least 1 dose of study drug. Due to early study termination, Part 2 was never initiated. | Posted | Median | 95% Confidence Interval | months | Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of HMPL-306 | Blood samples were collected at the specified timepoints to determine Cmax of HMPL-306. | The PK parameters analysis set included all patients who received at least 1 dose of the study drug and had a sufficient PK profile to derive at least 1 PK parameter. Only those patients with data collected at specified timepoints are reported. Due to early study termination, Part 2 was never initiated. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter (ng/mL) | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Time to Peak Plasma Concentration (Tmax) of HMPL-306 | Blood samples were collected at the specified timepoints to determine Tmax of HMPL-306. | The PK parameters analysis set included all patients who received at least 1 dose of the study drug and had a sufficient PK profile to derive at least 1 PK parameter. Only those patients with data collected at specified timepoints are reported. Due to early study termination, Part 2 was never initiated. | Posted | Median | Full Range | hour | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of HMPL-306 | Blood samples were collected at the specified timepoints to determine AUC0-24 of HMPL-306. | The PK parameters analysis set included all patients who received at least 1 dose of the study drug and had a sufficient PK profile to derive at least 1 PK parameter. Only those patients with data collected at specified timepoints are reported. Due to early study termination, Part 2 was never initiated. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*ng/mL | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1 |
|
|
|
| Secondary | Parts 1 and 2: Maximum Inhibition Rate of Plasma 2-Hydroxyglutaric Acid (2-HG) | Blood samples were collected at the specified timepoints to determine plasma concentrations of 2-HG which was a PD marker. The maximum inhibition rate of 2-HG for patients in different dose groups is presented. | The PD analysis set included all patients with at least 1 quantifiable level of 2-HG in plasma. Due to early study termination, Part 2 was never initiated. | Posted | Mean | Standard Deviation | percentage of inhibition | From screening (Day -28) until end of treatment, approximately 42 months for Part 1 |
|
|
|
| 0 |
| 3 |
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Part 1: Cohort-2: HMPL-306 100 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 100 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG002 | Part 1: Cohort-3: HMPL-306 150 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 150 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. | 1 | 5 | 2 | 5 | 4 | 5 |
| EG003 | Part 1: Cohort-4: HMPL-306 200 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 200 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. | 1 | 12 | 1 | 12 | 11 | 12 |
| EG004 | Part 1: Cohort-5: HMPL-306 250 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 250 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. | 2 | 6 | 0 | 6 | 5 | 6 |
| EG005 | Part 1: Cohort-6: HMPL-306 300 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 300 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. | 0 | 4 | 2 | 4 | 4 | 4 |
| EG006 | Part 1: Cohort-7: HMPL-306 350 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 350 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. | 0 | 4 | 1 | 4 | 4 | 4 |
| EG007 | Part 1: Cohort-8: HMPL-306 400 mg | Patients with locally advanced or metastatic solid tumors received HMPL-306 400 mg tablet orally QD in a 28-day continuous dosing treatment cycle until Pd, initiation of new anticancer therapy, withdrawal of consent, lost to follow-up, death, or the end of the study, whichever came first. Each cycle duration was 28 days. | 0 | 5 | 1 | 5 | 5 | 5 |
| Device related infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Neoplasm swelling | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 27.1 | Systematic Assessment |
|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 27.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Biliary obstruction | Hepatobiliary disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 27.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Rectal tenesmus | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Chronic gastritis | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Ejection fraction decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Blood calcium increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Blood creatine phosphokinase decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Prothrombin time prolonged | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA 27.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 27.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hemiplegia | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hypersomnia | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Physical deconditioning | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 27.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Locomotive syndrome | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Neutrophilia | Blood and lymphatic system disorders | MedDRA 27.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Skin plaque | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Obstructive sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
|
| Axillary vein thrombosis | Vascular disorders | MedDRA 27.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 27.1 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 27.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 27.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 27.1 | Systematic Assessment |
|
| Affect lability | Psychiatric disorders | MedDRA 27.1 | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA 27.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 27.1 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 27.1 | Systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA 27.1 | Systematic Assessment |
|
| Subretinal fluid | Eye disorders | MedDRA 27.1 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 27.1 | Systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA 27.1 | Systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009380 | Neoplasms, Nerve Tissue |
| TESAEs |
|
|
| Cycle 2 Day 1 |
|
|
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| Cycle 2 Day 1 |
|
|
|
| Cycle 2 Day 1 |
|
|