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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-001749-29 | EudraCT Number |
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This study will be conducted to assess the safety and tolerability of BOS172722 when administered as monotherapy and in combination with paclitaxel in participants with advanced nonhaematologic malignancies and also to establish the maximum tolerated dose and recommended Phase 2 dose of BOS172722 in combination with paclitaxel in those participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Monotherapy (BOS172722) | Experimental | BOS172722 will be administered on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycles in participants with histopathologically confirmed advanced nonhaematologic malignancies. |
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| Part A: Combination therapy (BOS172722 + Paclitaxel) | Experimental | BOS172722 will be administered on Cycle 0 Day 1 and on Days 1, 2, 8, 9, 15, and 16 in Cycle 1 and subsequent 28-day cycles in participants with histopathologically confirmed advanced nonhaematologic malignancies. The participants will also receive 80 milligrams per meters squared (mg/m^2) paclitaxel as an intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle. During dose escalation, further exploration of the treatment schedule for the BOS172722-paclitaxel combination will be initiated. In such combination cohorts, BOS172722 will be administered with paclitaxel on Days 1, 8, and 15 only of each treatment cycle (except for Cycle 2 Day1), and will not be administered on Day 2, 9, and 16. These alternative schedules will be explored to further characterize the pharmacokinetics and tolerability of such a dosing regimen. |
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| Part B: Combination therapy (BOS172722 + Paclitaxel) | Experimental | Participants with triple-negative breast cancer will be treated with oral BOS172722 at the recommended Phase 2 dose (RP2D) established in Part A on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle and IV paclitaxel at 80 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BOS172722 | Drug | Oral capsules |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events (AEs) | An AE is any untoward medical occurrence and does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product (IP), whether or not related to the IP. AEs include pre-existing conditions that worsen. | a minimum of approximately 3 months |
| Number of participants with a dose-limiting toxicity (DLT) | A DLT is defined as any toxicity attributable to BOS172722 that occurs before the end of Cycle 1. | Cycle 1 (28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Part A Monotherapy: Plasma concentration of BOS172722 measured over 24 hours when administered alone | The plasma concentration of BOS172722 when administered as monotherapy will be characterized | Cycle 1: Day 1 |
| Part A Combination: Plasma concentration of BOS172722 and paclitaxel measured over 24 hours when administered either individually or in combination |
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Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
For Part A only, histopathologically confirmed diagnosis of an advanced nonhaematologic malignancy
For Part B only, histopathologically confirmed diagnosis of triple-negative breast cancer
No standard curative treatment or has declined standard therapy
Eastern Cooperative Oncology Group performance status 0 or 1, measured within 72 hours before the first BOS172722 or paclitaxel dose
Predicted life expectancy of ≥ 3 months
Adequate renal function (creatinine ≤ 1.5 × upper limit of normal [ULN] or glomerular filtration rate ≥ 50 milliliters per minute [mL/min])
Adequate hepatic function:
Adequate bone marrow function:
Mean corrected QT interval as calculated by the Fridericia correction formula < 470 milliseconds
Willingness to use adequate contraceptive methods
Capable of giving signed informed consent
Willingness to avoid direct sunlight and the use of tanning equipment during the study and for at least 30 days after the last BOS172722 dose
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Addenbrooks Hospital | Cambridge | United Kingdom | ||||
| Edinburgh Cancer Centre - Western General Hospital |
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| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
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| ID | Term |
|---|---|
| C000654191 | BOS172722 |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| Paclitaxel | Drug | IV infusion |
|
The plasma concentration of BOS172722 and paclitaxel will be characterized. |
| Cycle 0: Day 1; Cycle 1: Day 1; Cycle 2: Day 1 |
| Part B Expansion: Plasma concentration of BOS172722 and paclitaxel measured over 24 hours when administered in combination | The plasma concentration of BOS172722 and paclitaxel will be characterized. | Cycle 1: Days 1 and 8 or 15 |
| Objective response rate (ORR) | ORR is defined as the percentage of participants achieving the best overall response of confirmed partial response (PR) or complete response (CR), as determined by investigator review. Responses are assessed by the Investigators using Response Evaluation Criteria in Solid Tumours (RECIST) guideline version 1.1. | a minimum of approximately 3 months |
| Duration of response (DOR) | DOR is defined as the time from documentation of tumor response to disease progression. Responses are assessed by the Investigators using RECIST guideline version 1.1. | a minimum of approximately 3 months |
| Time to response (TTR) | TTR is defined as the time from the start of treatment to the first objective tumor response observed for participants who achieved a CR or PR. Responses are assessed by the Investigators using RECIST guideline version 1.1. | a minimum of approximately 3 months |
| Time to progression on study | Time to progression is defined as the time from treatment until objective tumor progression. This does not include deaths. Responses are assessed by the Investigators using RECIST guideline version 1.1. | a minimum of approximately 3 months |
| Edinburgh |
| United Kingdom |
| Royal Marsden | London | SM2 5NG | United Kingdom |
| D012871 |
| Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |