Advanced Solid Tumors
Conditions
Keywords
gynecologic tract cancer, ovarian cancer, primary peritoneum cancer, fallopian tube cancer, uterine cancer, cervical cancer, vulvar cancer, vaginal cancer, clear cell histology, mucinous adenocarcinoma, carcinosarcoma, serous adenocarcinoma, neuroendocrine histology, small cell histology, small-molecule pdl1 inhibitor, tyrosine kinase inhibitor, combination therapy
Brief summary
This study is being conducted to evaluate the safety and tolerability of INCB099280 in combination with axitinib and to assess the antitumor activity of INCB099280 in combination with axitinib. This study will only be open in the UK and EU.
Interventions
DRUGINCB099280
Administered as specified in the treatment arm description
DRUGaxitinib
Administered as specified in the treatment arm description
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of 2 parts. In the Part 1 dose-escalation, participants will be enrolled in up to 6 dose levels of INCB099280 administered in combination with axitinib. In the Part 2 dose expansion, participants will be enrolled into 1 of 2 disease-specific cohorts at the dose(s) identified in Part 1.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed advanced solid tumors (protocol-defined select solid tumors) with measurable lesions per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) that are considered non-amenable to surgery or other curative treatments or procedures. * Must have disease progression on or after treatment with at least one prior systemic chemotherapy. * Eastern Cooperative Oncology Group performance status score of 0 or 1. * Life expectancy \> 12 weeks. * Willingness to avoid pregnancy.
Exclusion criteria
* Known additional malignancy that is progressing or requires active treatment. * Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease. * Toxicity from prior therapy that has not recovered to protocol-defined limits. * Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL-2, 4-1BB, CAR-T cell). * Prior therapy with antiangiogenic small-molecule TKIs targeting the VEGF pathway * Participation in another interventional clinical study while receiving INCB099280. * Impaired cardiac function or clinically significant cardiac disease. * History or evidence of interstitial lung disease including noninfectious pneumonitis. * Presence of gastrointestinal conditions that may affect drug absorption. * Any autoimmune disease requiring systemic treatment in the past 5 years. * Diagnosis of primary immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent. * Active infection requiring systemic therapy. * History of organ transplantation, including stem cell transplantation. * Receipt of systemic antibiotics within 28 days of first dose of study treatment. * Probiotic usage is prohibited during screening and throughout the study treatment period. * Received a live vaccine within 28 days of the planned start of study drug. * Laboratory values outside the Protocol-defined ranges. * Inadequate organ function. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) | up to 3 weeks | Any adverse event that ws at least possibly related to study treatment and met protocol-specified criteria was classified as a DLT. For the purpose of dose finding, decisions on dose were based on DLTs observed during the first 21 days of treatment. |
| Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to approximately 1 year | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE therefore could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or the start of new anticancer therapy. |
| Part 1: Number of Participants With TEAEs Leading to a Dosing Modification (Treatment Interruption, Dose Reduction, and Permanent Discontinuation of Either Study Drug) | up to approximately 1 year | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE therefore could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or the start of new anticancer therapy. |
| Part 2: Objective Response | up to 2 years | Objective response was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With Any TEAE | up to 2 years | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE therefore could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or the start of new anticancer therapy. |
| Part 2: Number of Participants With TEAEs Leading to a Dosing Modification (Treatment Interruption, Dose Reduction, and Permanent Discontinuation of Either Study Drug) | up to 2 years | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE therefore could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was either reported for the first time or the worsening of a pre-existing event after the first dose of either study drug until 104 days after the last dose of study treatment or the start of new anticancer therapy. |
| Part 1: Objective Response | up to 335 days | Objective response was defined as the percentage of participants with a BOR of CR or PR by investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. |
| Part 1: Disease Control | up to 335 days | Disease control was defined as the percentage of participants with a BOR of CR, PR, or stable disease (SD) by investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD. |
| Part 1: Duration of Response (DOR) | up to 335 days | DOR was defined as the time from the first CR or PR until disease progression by investigator assessment per RECIST v1.1 or death from any cause, whichever occurred earlier. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. |
| Part 1: INCB099280 and Axitinib Plasma Concentrations | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | Blood samples were collected for the analysis of INCB099280 and axitinib concentrations. Per Protocol, PK samples for axitinib were only to be analyzed in case of a concern that axitinib was not as active as expected. Due to the early termination of the study before readout, these samples were not analyzed. |
| Part 1: Cmax of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | Cmax was defined as the maximum observed concentration of INCB099280. |
| Part 1: Tmax of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | tmax was defined as the time to the maximum concentration of INCB099280. |
| Part 1: AUC0-4h of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | AUC0-4h was defined as area under the steady-state plasma or serum concentration-time curve from 0 to 4 hours. |
| Part 1: Cmax,ss of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | Cmax,ss was defined as the maximum observed concentration at steady state. |
| Part 1: Tmax,ss of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | tmax,ss was defined as the time to the maximum concentration of INCB099280 at steady state. |
| Part 1: AUC0-12h of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | AUC0-12h was defined as the area under the steady-state plasma or serum concentration-time curve from 0 to 12 hours. |
| Part 1: Cavg of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | Cavg was defined as the average concentration of INCB099280. |
| Part 1: Ctau of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | Ctau was defined as the concentration of INCB099280 at the end of a dose interval. |
| Part 1: t1/2 of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | t1/2 was defined as the apparent terminal-phase disposition half life of INCB099280. |
| Part 1: CLss/F of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | CLss/F was defined as the apparent oral dose clearance of INCB099280 at steady state. |
| Part 1: Vz/F of INCB099280 When Administered With Axitinib | Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, and Cycle 8 Day 1: before INCB099280 and axitinib dose. Cycle 1 Day 1 and Cycle 2 Day 1: 1, 2, and 4 hours after INCB099280 dose. End-of-trial visit: axitinib sample | Vz/F was defined as the apparent oral dose volume of distribution of INCB099280. |
Countries
United Kingdom
Contacts
STUDY_DIRECTORPhilomena Colucci
Incyte Corporation
Participant flow
Pre-assignment details
This study was conducted at 3 study centers in the United Kingdom.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 10.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
None listed