| analysis_cohort | phase | dose_level | n |
|---|---|---|---|
| Phase I non-RP2D | Phase I | Phase I dose level 1: 400 mg BID | 3 |
| Phase I non-RP2D | Phase I | Phase I dose level 2: 600 mg BID | 3 |
| RP2D / Phase II efficacy population | Phase I | Phase I dose level 3/RP2D: 800 mg BID | 6 |
| RP2D / Phase II efficacy population | Phase II | Phase II/RP2D: 800 mg BID | 24 |
BTCRC-LYM20-463: A basic final study report
A Single Arm Phase I/II Study of Tazemetostat with Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma
Analysis population
For this draft table, We summarize all registered subjects with available demographic data. The table is stratified by a working analysis cohort:
- Phase I non-RP2D: Phase I subjects treated below the RP2D dose level
- RP2D / Phase II efficacy population: Phase II subjects plus Phase I subjects treated at the RP2D dose level
Demographics and baseline characteristics
| Characteristic |
Analysis cohort
|
||
|---|---|---|---|
| Phase I non-RP2D N = 61 |
RP2D / Phase II efficacy population N = 301 |
Overall N = 361 |
|
| Age at registration, years | |||
| Median (Q1, Q3) | 66.5 (64.0, 70.0) | 57.5 (50.0, 67.0) | 58.5 (50.5, 68.0) |
| Min, Max | 44.0, 70.0 | 35.0, 76.0 | 35.0, 76.0 |
| Sex | |||
| Female | 1 (16.7%) | 17 (56.7%) | 18 (50.0%) |
| Male | 5 (83.3%) | 13 (43.3%) | 18 (50.0%) |
| Race | |||
| Asian | 0 (0.0%) | 2 (6.7%) | 2 (5.6%) |
| Unknown | 0 (0.0%) | 2 (6.7%) | 2 (5.6%) |
| White | 6 (100.0%) | 26 (86.7%) | 32 (88.9%) |
| Ethnicity | |||
| Hispanic or Latino | 0 (0.0%) | 3 (10.0%) | 3 (8.3%) |
| Non-Hispanic | 6 (100.0%) | 26 (86.7%) | 32 (88.9%) |
| Unknown | 0 (0.0%) | 1 (3.3%) | 1 (2.8%) |
| Study site | |||
| 1 S Park St Medical Center | 1 (16.7%) | 2 (6.7%) | 3 (8.3%) |
| Northwestern Memorial Hospital | 0 (0.0%) | 5 (16.7%) | 5 (13.9%) |
| OSU James Outpatient Care - West Campus | 1 (16.7%) | 9 (30.0%) | 10 (27.8%) |
| Rutgers Cancer Institute of New Jersey | 4 (66.7%) | 4 (13.3%) | 8 (22.2%) |
| RWJ Barnabas Health Cooperman Barnabas Medical Center | 0 (0.0%) | 1 (3.3%) | 1 (2.8%) |
| University of Illinois Hospital and Health Systems (Outpatient Cancer Center) | 0 (0.0%) | 1 (3.3%) | 1 (2.8%) |
| University of Wisconsin Carbone Cancer Center - University Hospital | 0 (0.0%) | 5 (16.7%) | 5 (13.9%) |
| UW Health Eastpark Medical Center | 0 (0.0%) | 3 (10.0%) | 3 (8.3%) |
| Study phase | |||
| Phase I | 6 (100.0%) | 6 (20.0%) | 12 (33.3%) |
| Phase II | 0 (0.0%) | 24 (80.0%) | 24 (66.7%) |
| Tazemetostat dose cohort | |||
| Phase I dose level 1: 400 mg BID | 3 (50.0%) | 0 (0.0%) | 3 (8.3%) |
| Phase I dose level 2: 600 mg BID | 3 (50.0%) | 0 (0.0%) | 3 (8.3%) |
| Phase I dose level 3/RP2D: 800 mg BID | 0 (0.0%) | 6 (20.0%) | 6 (16.7%) |
| Phase II/RP2D: 800 mg BID | 0 (0.0%) | 24 (80.0%) | 24 (66.7%) |
| ECOG performance status | |||
| 0 | 5 (83.3%) | 19 (63.3%) | 24 (66.7%) |
| 1 | 1 (16.7%) | 11 (36.7%) | 12 (33.3%) |
| 2 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Height, cm | |||
| Median (Q1, Q3) | 173.4 (171.5, 179.7) | 165.1 (157.5, 172.7) | 166.5 (157.5, 175.3) |
| Min, Max | 154.9, 185.4 | 151.0, 184.0 | 151.0, 185.4 |
| Missing | 0 | 1 | 1 |
| Weight, kg | |||
| Median (Q1, Q3) | 101.7 (90.9, 103.0) | 83.1 (71.9, 97.5) | 84.4 (71.9, 102.3) |
| Min, Max | 67.2, 104.0 | 44.5, 130.2 | 44.5, 130.2 |
| Missing | 0 | 1 | 1 |
| BMI, kg/m^2 | |||
| Median (Q1, Q3) | 31.3 (29.8, 34.0) | 31.0 (25.4, 34.9) | 31.3 (26.1, 34.3) |
| Min, Max | 28.0, 34.3 | 19.5, 45.1 | 19.5, 45.1 |
| Missing | 0 | 2 | 2 |
| WHO-HAEM4R grade | |||
| Grade 1 | 0 (0.0%) | 3 (10.0%) | 3 (8.3%) |
| Grade 2 | 5 (83.3%) | 10 (33.3%) | 15 (41.7%) |
| Grade 3A | 1 (16.7%) | 5 (16.7%) | 6 (16.7%) |
| Criteria not applicable | 0 (0.0%) | 12 (40.0%) | 12 (33.3%) |
| WHO-HAEM5 classification | |||
| Classic follicular lymphoma | 6 (100.0%) | 23 (76.7%) | 29 (80.6%) |
| Criteria not applicable | 0 (0.0%) | 7 (23.3%) | 7 (19.4%) |
| Ann Arbor stage | |||
| II | 0 (0.0%) | 4 (13.3%) | 4 (11.1%) |
| III | 2 (33.3%) | 15 (50.0%) | 17 (47.2%) |
| IV | 4 (66.7%) | 11 (36.7%) | 15 (41.7%) |
| Number of GELF criteria | |||
| 1 | 5 (83.3%) | 16 (53.3%) | 21 (58.3%) |
| 2 | 1 (16.7%) | 11 (36.7%) | 12 (33.3%) |
| 3 | 0 (0.0%) | 3 (10.0%) | 3 (8.3%) |
| Number of FLIPI 1 risk factors | |||
| 1 | 0 (0.0%) | 6 (23.1%) | 6 (18.8%) |
| 2 | 4 (66.7%) | 15 (57.7%) | 19 (59.4%) |
| 3 | 1 (16.7%) | 3 (11.5%) | 4 (12.5%) |
| 4 | 1 (16.7%) | 2 (7.7%) | 3 (9.4%) |
| Missing | 0 | 4 | 4 |
| Number of FLIPI 2 risk factors | |||
| 1 | 5 (83.3%) | 14 (87.5%) | 19 (86.4%) |
| 2 | 1 (16.7%) | 2 (12.5%) | 3 (13.6%) |
| Missing | 0 | 14 | 14 |
| 1 n (%) | |||
| RP2D / Phase II efficacy population is defined here as all Phase II subjects plus Phase I subjects treated at dose level 3 (800 mg twice daily). Confirm this definition before final report lock. | |||
| Continuous variables are summarized as median (Q1, Q3) and range. Categorical variables are summarized as n (%). | |||
Safety analysis
For this draft safety analysis, the safety population includes all subjects with a non-missing treatment start date. Treatment-emergent adverse events (TEAEs) are defined as adverse events with start date on or after the first protocol treatment date. Records coded as pre-existing conditions are excluded.
Because adverse event records can be repeated across visits or updated under different FORM_STATUS values, AE records are collapsed to an event-level dataset defined by subject, AE term, other-specify text, and AE start date. For repeated/updated records for the same event, the maximum toxicity grade and any positive serious/DLT/relatedness/action flags are retained.
| Safety overview | |||
|---|---|---|---|
| Safety summary | Phase I non-RP2D | RP2D / Phase II efficacy population | Overall |
| Safety population | 6 | 30 | 36 |
| Any TEAE | 6/6 (100.0%) | 30/30 (100.0%) | 36/36 (100.0%) |
| Any Grade ≥3 TEAE | 2/6 (33.3%) | 25/30 (83.3%) | 27/36 (75.0%) |
| Any Grade ≥4 TEAE | 0/6 (0.0%) | 12/30 (40.0%) | 12/36 (33.3%) |
| Any Grade 5 TEAE | 0/6 (0.0%) | 0/30 (0.0%) | 0/36 (0.0%) |
| Any serious TEAE | 1/6 (16.7%) | 9/30 (30.0%) | 10/36 (27.8%) |
| Any study-drug-related TEAE | 4/6 (66.7%) | 30/30 (100.0%) | 34/36 (94.4%) |
| Any study-drug-related Grade ≥3 TEAE | 2/6 (33.3%) | 25/30 (83.3%) | 27/36 (75.0%) |
| Any TEAE leading to study treatment action | 3/6 (50.0%) | 15/30 (50.0%) | 18/36 (50.0%) |
| Any TEAE leading to treatment discontinuation | 0/6 (0.0%) | 0/30 (0.0%) | 0/36 (0.0%) |
| Any dose-limiting toxicity | 0/6 (0.0%) | 1/30 (3.3%) | 1/36 (2.8%) |
RP2D efficacy analysis
The RP2D efficacy population is defined as Phase II subjects plus Phase I subjects treated at dose level 3 / RP2D. Binary response endpoints are summarized as n/N (%) with exact 95% binomial confidence intervals. Subjects with missing endpoint status are excluded from the corresponding evaluable analysis and listed separately.
| RP2D efficacy population data checks | |
|---|---|
| Check | N |
| RP2D subjects | 30 |
| CMR evaluable | 29 |
| ORR evaluable | 29 |
| DOR evaluable | 29 |
| Pre-Cycle 4 response evaluable | 29 |
| PFS status available | 30 |
| OS status available | 30 |
| RP2D efficacy response endpoints | ||
|---|---|---|
| Endpoint | Responders / evaluable (%) | Denominator definition |
| Primary endpoint: End-of-treatment CMR | 28/29 (96.6%; 95% CI 82.2%, 99.9%) | Subjects with non-missing CMRSTAT |
| Supportive endpoint: End-of-treatment ORR | 29/29 (100.0%; 95% CI 88.1%, 100.0%) | Subjects with non-missing ORRSTAT |
| Secondary endpoint: CMR after 3 cycles | 23/29 (79.3%; 95% CI 60.3%, 92.0%) | Subjects with evaluable pre-Cycle 4 response |
| Secondary endpoint: ORR after 3 cycles | 29/29 (100.0%; 95% CI 88.1%, 100.0%) | Subjects with evaluable pre-Cycle 4 response |
| Exact 95% confidence intervals are based on the binomial distribution. | ||
| ORR is defined as CMR + PMR. Subjects with missing or non-evaluable response are excluded from the corresponding evaluable endpoint denominator. | ||
| Duration of response in the RP2D efficacy population | |
|---|---|
| Measure | Value |
| DOR-evaluable responders | 29 |
| DOR events | 0 |
| Censored | 29 |
| Mean DOR time, months | 3.64 (95% CI 3.34, 3.93) |
| Median DOR time, months | 3.84 |
| Min, max DOR time, months | 0.00, 4.24 |
| DOR is summarized among subjects with non-missing DOR status and DOR time in the endpoint file. | |
| Exploratory PFS and OS summaries from endpoint file | |||||
|---|---|---|---|---|---|
| Endpoint | N | Events | Censored | Median follow-up/time, months | Min, max time, months |
| PFS | 30 | 0 | 30 | 6.64 | 1.68, 7.36 |
| OS | 30 | 0 | 30 | 12.23 | 6.47, 24.41 |
| These summaries use the current endpoint file as provided. PFS and OS should be reconciled with long-term follow-up forms before final report lock. | |||||
Appendix
Detailed safety data
| Treatment-emergent adverse events | |||||
|---|---|---|---|---|---|
| AE term | SOC | All grades | Grade ≥3 | Max grade | Events |
| ANEMIA | BLOOD AND LYMPHATIC SYSTEM DISORDERS | 24 (66.7%) | 3 (8.3%) | 3 | 48 |
| LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 22 (61.1%) | 20 (55.6%) | 4 | 92 |
| WHITE BLOOD CELL DECREASED | INVESTIGATIONS | 20 (55.6%) | 6 (16.7%) | 4 | 64 |
| NAUSEA | GASTROINTESTINAL DISORDERS | 20 (55.6%) | 1 (2.8%) | 3 | 31 |
| PLATELET COUNT DECREASED | INVESTIGATIONS | 20 (55.6%) | 0 (0.0%) | 2 | 30 |
| NEUTROPHIL COUNT DECREASED | INVESTIGATIONS | 15 (41.7%) | 8 (22.2%) | 4 | 32 |
| FATIGUE | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 14 (38.9%) | 0 (0.0%) | 2 | 17 |
| CREATININE INCREASED | INVESTIGATIONS | 13 (36.1%) | 0 (0.0%) | 2 | 20 |
| DYSGEUSIA | NERVOUS SYSTEM DISORDERS | 13 (36.1%) | 0 (0.0%) | 2 | 18 |
| BLOOD LACTATE DEHYDROGENASE INCREASED | INVESTIGATIONS | 12 (33.3%) | 0 (0.0%) | 1 | 13 |
| CONSTIPATION | GASTROINTESTINAL DISORDERS | 12 (33.3%) | 0 (0.0%) | 2 | 15 |
| HYPERURICEMIA | METABOLISM AND NUTRITION DISORDERS | 10 (27.8%) | 0 (0.0%) | 1 | 12 |
| HYPONATREMIA | METABOLISM AND NUTRITION DISORDERS | 10 (27.8%) | 0 (0.0%) | 1 | 14 |
| VOMITING | GASTROINTESTINAL DISORDERS | 10 (27.8%) | 0 (0.0%) | 1 | 15 |
| INFUSION RELATED REACTION | INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 9 (25.0%) | 2 (5.6%) | 3 | 9 |
| HEADACHE | NERVOUS SYSTEM DISORDERS | 9 (25.0%) | 1 (2.8%) | 3 | 14 |
| ALANINE AMINOTRANSFERASE INCREASED | INVESTIGATIONS | 9 (25.0%) | 0 (0.0%) | 2 | 12 |
| ASPARTATE AMINOTRANSFERASE INCREASED | INVESTIGATIONS | 9 (25.0%) | 0 (0.0%) | 2 | 10 |
| HYPOKALEMIA | METABOLISM AND NUTRITION DISORDERS | 9 (25.0%) | 0 (0.0%) | 2 | 19 |
| ANOREXIA | METABOLISM AND NUTRITION DISORDERS | 8 (22.2%) | 1 (2.8%) | 3 | 11 |
| DIARRHEA | GASTROINTESTINAL DISORDERS | 8 (22.2%) | 0 (0.0%) | 2 | 11 |
| HYPERGLYCEMIA | METABOLISM AND NUTRITION DISORDERS | 8 (22.2%) | 0 (0.0%) | 2 | 11 |
| ALOPECIA | SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 7 (19.4%) | 0 (0.0%) | 2 | 8 |
| EDEMA LIMBS | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 7 (19.4%) | 0 (0.0%) | 2 | 7 |
| FEVER | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 7 (19.4%) | 0 (0.0%) | 2 | 10 |
| HYPOALBUMINEMIA | METABOLISM AND NUTRITION DISORDERS | 7 (19.4%) | 0 (0.0%) | 2 | 11 |
| WEIGHT LOSS | INVESTIGATIONS | 7 (19.4%) | 0 (0.0%) | 2 | 10 |
| HYPERHIDROSIS | SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 6 (16.7%) | 0 (0.0%) | 2 | 6 |
| INSOMNIA | PSYCHIATRIC DISORDERS | 5 (13.9%) | 1 (2.8%) | 3 | 7 |
| DIZZINESS | NERVOUS SYSTEM DISORDERS | 5 (13.9%) | 0 (0.0%) | 1 | 6 |
| DYSPEPSIA | GASTROINTESTINAL DISORDERS | 5 (13.9%) | 0 (0.0%) | 2 | 5 |
| MUCOSITIS ORAL | GASTROINTESTINAL DISORDERS | 5 (13.9%) | 0 (0.0%) | 2 | 6 |
| ALKALINE PHOSPHATASE INCREASED | INVESTIGATIONS | 4 (11.1%) | 0 (0.0%) | 1 | 4 |
| HYPERPHOSPHATEMIA | METABOLISM AND NUTRITION DISORDERS | 4 (11.1%) | 0 (0.0%) | 1 | 5 |
| HYPOCALCEMIA | METABOLISM AND NUTRITION DISORDERS | 4 (11.1%) | 0 (0.0%) | 2 | 8 |
| FEBRILE NEUTROPENIA | BLOOD AND LYMPHATIC SYSTEM DISORDERS | 3 (8.3%) | 3 (8.3%) | 3 | 3 |
| BONE PAIN | MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | 3 (8.3%) | 1 (2.8%) | 3 | 6 |
| URINARY TRACT INFECTION | INFECTIONS AND INFESTATIONS | 3 (8.3%) | 1 (2.8%) | 3 | 3 |
| ARTHRALGIA | MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | 3 (8.3%) | 0 (0.0%) | 2 | 6 |
| BLOATING | GASTROINTESTINAL DISORDERS | 3 (8.3%) | 0 (0.0%) | 2 | 3 |
| BLOOD BICARBONATE DECREASED | INVESTIGATIONS | 3 (8.3%) | 0 (0.0%) | 1 | 5 |
| BLOOD BILIRUBIN INCREASED | INVESTIGATIONS | 3 (8.3%) | 0 (0.0%) | 1 | 3 |
| COUGH | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | 3 (8.3%) | 0 (0.0%) | 2 | 3 |
| DYSPNEA | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | 3 (8.3%) | 0 (0.0%) | 1 | 4 |
| FLU LIKE SYMPTOMS | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 3 (8.3%) | 0 (0.0%) | 2 | 3 |
| PAIN | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 3 (8.3%) | 0 (0.0%) | 1 | 3 |
| PALPITATIONS | CARDIAC DISORDERS | 3 (8.3%) | 0 (0.0%) | 2 | 4 |
| PRODUCTIVE COUGH | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | 3 (8.3%) | 0 (0.0%) | 1 | 3 |
| PRURITUS | SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 3 (8.3%) | 0 (0.0%) | 1 | 3 |
| RASH MACULO-PAPULAR | SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 3 (8.3%) | 0 (0.0%) | 1 | 4 |
| UPPER RESPIRATORY INFECTION | INFECTIONS AND INFESTATIONS | 3 (8.3%) | 0 (0.0%) | 2 | 3 |
| HYPERTENSION | VASCULAR DISORDERS | 2 (5.6%) | 1 (2.8%) | 3 | 4 |
| INFECTIONS AND INFESTATIONS - OTHER, SPECIFY | INFECTIONS AND INFESTATIONS | 2 (5.6%) | 1 (2.8%) | 3 | 4 |
| SINUS TACHYCARDIA | CARDIAC DISORDERS | 2 (5.6%) | 1 (2.8%) | 3 | 3 |
| ACUTE KIDNEY INJURY | RENAL AND URINARY DISORDERS | 1 (2.8%) | 1 (2.8%) | 3 | 1 |
| ATRIAL FIBRILLATION | CARDIAC DISORDERS | 1 (2.8%) | 1 (2.8%) | 3 | 2 |
| FALL | INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 1 (2.8%) | 1 (2.8%) | 3 | 1 |
| GENERALIZED MUSCLE WEAKNESS | MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | 1 (2.8%) | 1 (2.8%) | 3 | 3 |
| GLUCOSE INTOLERANCE | METABOLISM AND NUTRITION DISORDERS | 1 (2.8%) | 1 (2.8%) | 4 | 2 |
| IMMUNE SYSTEM DISORDERS - OTHER, SPECIFY | IMMUNE SYSTEM DISORDERS | 1 (2.8%) | 1 (2.8%) | 3 | 2 |
| LUNG INFECTION | INFECTIONS AND INFESTATIONS | 1 (2.8%) | 1 (2.8%) | 3 | 1 |
| SKIN INFECTION | INFECTIONS AND INFESTATIONS | 1 (2.8%) | 1 (2.8%) | 3 | 1 |
| THROMBOEMBOLIC EVENT | VASCULAR DISORDERS | 1 (2.8%) | 1 (2.8%) | 3 | 2 |
| TUMOR LYSIS SYNDROME | METABOLISM AND NUTRITION DISORDERS | 1 (2.8%) | 1 (2.8%) | 3 | 1 |
| Serious TEAEs, DLTs, and Grade ≥4 TEAEs | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Subject | Cohort | Start date | End date | Preferred term | System organ class | Maximum grade | Serious | DLT | Related to | Treatment action taken |
| B463-1005 | Phase I non-RP2D | 2023-12-24 | 2023-12-28 | LUNG INFECTION | INFECTIONS AND INFESTATIONS | 3 | Yes | No | bendamustine, rituximab, tazemetostat | Yes |
| B463-1007 | RP2D / Phase II efficacy population | 2023-12-21 | 2024-01-09 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1007 | RP2D / Phase II efficacy population | 2023-12-21 | 2023-12-23 | FEVER | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 1 | Yes | No | bendamustine, rituximab | Yes |
| B463-1007 | RP2D / Phase II efficacy population | 2024-03-05 | 2024-04-02 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1008 | RP2D / Phase II efficacy population | 2023-12-15 | 2024-01-02 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | rituximab | No |
| B463-1008 | RP2D / Phase II efficacy population | 2023-12-22 | 2024-01-03 | INFECTIONS AND INFESTATIONS - OTHER, SPECIFY | INFECTIONS AND INFESTATIONS | 2 | Yes | No | None recorded | Yes |
| B463-1008 | RP2D / Phase II efficacy population | 2024-01-31 | 2024-02-13 | NEUTROPHIL COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab | Yes |
| B463-1008 | RP2D / Phase II efficacy population | 2024-02-21 | 2024-02-25 | ATRIAL FIBRILLATION | CARDIAC DISORDERS | 3 | Yes | No | bendamustine, rituximab | Yes |
| B463-1009 | RP2D / Phase II efficacy population | 2024-01-31 | 2024-02-14 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, tazemetostat | No |
| B463-1009 | RP2D / Phase II efficacy population | 2024-02-05 | 2024-02-05 | SUPERFICIAL THROMBOPHLEBITIS | VASCULAR DISORDERS | 2 | Yes | No | None recorded | No |
| B463-1012 | RP2D / Phase II efficacy population | 2024-02-20 | 2024-02-21 | INFUSION RELATED REACTION | INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 3 | Yes | No | rituximab | No |
| B463-1012 | RP2D / Phase II efficacy population | 2024-03-19 | 2024-03-21 | ACUTE KIDNEY INJURY | RENAL AND URINARY DISORDERS | 3 | Yes | No | None recorded | No |
| B463-1012 | RP2D / Phase II efficacy population | 2024-03-21 | 2024-03-26 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1012 | RP2D / Phase II efficacy population | 2024-04-08 | 2024-04-22 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1012 | RP2D / Phase II efficacy population | 2024-04-29 | 2024-06-18 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1013 | RP2D / Phase II efficacy population | 2024-07-01 | 2024-07-15 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab | No |
| B463-1015 | RP2D / Phase II efficacy population | 2024-06-19 | 2024-06-22 | THROMBOEMBOLIC EVENT | VASCULAR DISORDERS | 3 | Yes | No | None recorded | Yes |
| B463-1015 | RP2D / Phase II efficacy population | 2024-08-07 | 2024-08-26 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1016 | RP2D / Phase II efficacy population | 2024-09-06 | 2024-09-12 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1016 | RP2D / Phase II efficacy population | 2024-12-02 | 2024-12-11 | NEUTROPHIL COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, tazemetostat | Yes |
| B463-1016 | RP2D / Phase II efficacy population | 2024-12-11 | 2024-12-16 | WHITE BLOOD CELL DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, tazemetostat | Yes |
| B463-1018 | RP2D / Phase II efficacy population | 2024-12-03 | NA | HYPOGLYCEMIA | METABOLISM AND NUTRITION DISORDERS | 2 | Yes | No | None recorded | No |
| B463-1020 | RP2D / Phase II efficacy population | 2024-12-17 | 2024-12-29 | GLUCOSE INTOLERANCE | METABOLISM AND NUTRITION DISORDERS | 4 | No | No | None recorded | No |
| B463-1022 | RP2D / Phase II efficacy population | 2024-12-23 | NA | HYPERTENSION | VASCULAR DISORDERS | 3 | Yes | No | None recorded | No |
| B463-1022 | RP2D / Phase II efficacy population | 2025-02-22 | 2025-02-28 | URINARY TRACT INFECTION | INFECTIONS AND INFESTATIONS | 3 | Yes | No | None recorded | Yes |
| B463-1025 | RP2D / Phase II efficacy population | 2025-05-13 | 2025-05-20 | NEUTROPHIL COUNT DECREASED | INVESTIGATIONS | 4 | No | Yes | bendamustine, tazemetostat | Yes |
| B463-1028 | RP2D / Phase II efficacy population | 2025-04-07 | 2025-04-11 | SKIN INFECTION | INFECTIONS AND INFESTATIONS | 3 | Yes | No | None recorded | Yes |
| B463-1028 | RP2D / Phase II efficacy population | 2025-06-05 | 2025-06-19 | NEUTROPHIL COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, tazemetostat | No |
| B463-1031 | RP2D / Phase II efficacy population | 2025-06-17 | 2025-06-20 | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1031 | RP2D / Phase II efficacy population | 2025-06-17 | 2025-06-26 | NEUTROPHIL COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1031 | RP2D / Phase II efficacy population | 2025-06-17 | 2025-06-20 | WHITE BLOOD CELL DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine, rituximab, tazemetostat | No |
| B463-1031 | RP2D / Phase II efficacy population | 2025-06-22 | 2025-06-28 | FEBRILE NEUTROPENIA | BLOOD AND LYMPHATIC SYSTEM DISORDERS | 3 | Yes | No | bendamustine, rituximab, tazemetostat | Yes |
| B463-1031 | RP2D / Phase II efficacy population | 2025-06-23 | 2025-07-01 | IMMUNE SYSTEM DISORDERS - OTHER, SPECIFY | IMMUNE SYSTEM DISORDERS | 3 | Yes | No | None recorded | Yes |
| B463-1031 | RP2D / Phase II efficacy population | 2025-07-01 | 2025-08-09 | IMMUNE SYSTEM DISORDERS - OTHER, SPECIFY | IMMUNE SYSTEM DISORDERS | 2 | Yes | No | None recorded | Yes |
| B463-1035 | RP2D / Phase II efficacy population | 2025-07-31 | NA | LYMPHOCYTE COUNT DECREASED | INVESTIGATIONS | 4 | No | No | bendamustine | No |
| Listing includes all event-level TEAEs that were serious, dose-limiting, or Grade ≥4. | ||||||||||
Additional efficacy data
| RP2D efficacy records with missing endpoint data | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subject | Phase | Dose cohort | Cycles received | Cycle 4 response | Final Lugano response | CMRSTAT | ORRSTAT | DORSTAT | Comments |
| B463-1020 | Phase II | Phase II/RP2D: 800 mg BID | 2 | NA | PMR | NA | NA | NA | The subject discontinued treatment after Cycle 2 due to Grade 3 nausea. PMR was recorded at the safety visit (D30). Is this subject evaluable for efficacy endpoints?CMR, ORR and DOR status have been left blank. |
| Subjects listed here are excluded from the corresponding evaluable endpoint denominator unless otherwise specified. | |||||||||
| Protocol decision-rule summary for primary CMR endpoint | |||
|---|---|---|---|
| Observed primary CMR count | CMR-evaluable denominator | Protocol final success boundary | Draft interpretation |
| 28 | 29 | Reject H0 if >11 CMR among 27 evaluable subjects on the Ha1 path; or >10 CMR among 26 evaluable subjects on the Ha2 path | Observed CMR count exceeds the protocol final success boundary; confirm final evaluable denominator with study team. |
| The current endpoint file contains 30 RP2D subjects and 29 subjects with non-missing CMRSTAT. The protocol specifies up to 27 evaluable subjects, with non-evaluable subjects replaced. Confirm final analysis denominator before report lock. | |||
One important point: the current endpoint file appears to have 30 RP2D subjects, but 29 CMR/ORR/DOR evaluable records because subject B463-1020 has missing CMR/ORR/DOR status after discontinuing after Cycle 2. The code flags this automatically in the missing endpoint listing.