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This is a Phase 1, first-in-human, dose escalation study in participants with advanced solid tumors to determine the pharmacokinetics, maximum tolerated dose and the recommended Phase 2 dose of ABBV-075 at different monotherapy dosing schedules. In addition the study will evaluate the safety. tolerability and the pharmacokinetics of ABBV-075 monotherapy or combination therapy in disease specific expansion cohorts.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABBV-075 | Experimental | Dose escalation cohorts of ABBV-075 monotherapy |
|
| ABBV-075 and venetoclax combination | Experimental | Expansion cohorts of ABBV-075 and venetoclax combination therapy |
|
| ABBV-075 expansion | Experimental | Expansion cohorts of ABBV-075 monotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABBV-075 | Drug | ABBV-075 Oral tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose of ABBV-075 | Maximum tolerated dose is defined as the highest dose level at which less than 2 of 6 participants experience the same dose limiting toxicity. If more than 2 participants experience a different dose limiting toxicity, the maximum tolerated dose may be further evaluated or determined to be exceeded based on discussions with the investigators and medical monitors. | Minimum first cycle of dosing (28 days) up to one year for dose escalation segment. |
| Time to Cmax (peak time, Tmax) for ABBV-075 | Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years. | |
| Number of participants with adverse events | Screening, Cycle 1 Day 1, 8 and 15, then Day 1 of each cycle up to approximately 2 years. | |
| Maximum observed plasma concentration (Cmax) of ABBV-075 | Approximately 24 hours following a single dose of ABBV-075 up to approximately 2 years. | |
| Area under the curve (AUC) | Area under the plasma concentration versus time curve from time 0 (pre-dose) to the time of the last measurable concentration (AUC 0-t). | Cycle 1 Day 1 Pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post ABBV-075 dosing, and on Cycle 1 Day 15 at 14, 17, 20 hours post dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of overall response (DOR) | DOR is defined as the time from the participant's initial CR or PR to the time of disease progression | At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years. |
| Objective Response Rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| AbbVie Inc. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scottsdale Healthcare /ID# 132963 | Scottsdale | Arizona | 85258-4566 | United States | ||
| City of Hope /ID# 154053 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31420359 | Result | Piha-Paul SA, Sachdev JC, Barve M, LoRusso P, Szmulewitz R, Patel SP, Lara PN Jr, Chen X, Hu B, Freise KJ, Modi D, Sood A, Hutti JE, Wolff J, O'Neil BH. First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors. Clin Cancer Res. 2019 Nov 1;25(21):6309-6319. doi: 10.1158/1078-0432.CCR-19-0578. Epub 2019 Aug 16. | |
| 33934351 |
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| Venetoclax | Drug | Venetoclax tablets, film-coated |
|
|
ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR). |
| At screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years. |
| Progression Free Survival (PFS) | PFS is defined as the time from the first dose of ABBV-075 to either disease progression or death, whichever occurs first. | Screening, every 8 weeks from Cycle 1 Day 1, and at the Final visit up to approximately 2 years. |
| Duarte |
| California |
| 91010 |
| United States |
| UC Davis Comp Cancer Ctr /ID# 154644 | Sacramento | California | 95817 | United States |
| Yale University /ID# 136982 | New Haven | Connecticut | 06510 | United States |
| University of Chicago /ID# 155453 | Chicago | Illinois | 60637-1443 | United States |
| Indiana Univ School Medicine /ID# 132946 | Indianapolis | Indiana | 46202 | United States |
| Duke Univ Med Ctr /ID# 154647 | Durham | North Carolina | 27705 | United States |
| Mary Crowley Cancer Research /ID# 154059 | Dallas | Texas | 75230 | United States |
| Univ TX, MD Anderson /ID# 132276 | Houston | Texas | 77030 | United States |
| UT MD Anderson Cancer Center /ID# 164122 | Houston | Texas | 77030 | United States |
| Derived |
| Borthakur G, Odenike O, Aldoss I, Rizzieri DA, Prebet T, Chen C, Popovic R, Modi DA, Joshi RH, Wolff JE, Jonas BA. A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed/refractory acute myeloid leukemia. Cancer. 2021 Aug 15;127(16):2943-2953. doi: 10.1002/cncr.33590. Epub 2021 May 2. |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D001943 | Breast Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D015470 | Leukemia, Myeloid, Acute |
| D009101 | Multiple Myeloma |
| D011471 | Prostatic Neoplasms |
| D055752 | Small Cell Lung Carcinoma |
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D008223 | Lymphoma |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000621792 | mivebresib |
| C579720 | venetoclax |
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