Advanced Solid Tumors
Conditions
Keywords
locally advanced or metastatic solid tumors, (HR) positive (HR+) breast cancer, HER2 negative (HER2-) breast cancer
Brief summary
Study ATX-898-101 is a phase 1/2 open-label study evaluating the safety, tolerability, pharmacokinetic, and preliminary efficacy of ATX-898 as monotherapy and in combination with anti-neoplastic agents in selected solid tumors. This study consists of 2 parts. Part 1 evaluates ATX-898 as monotherapy and Part 2 evaluates ATX-898 in combination with anti-neoplastic agents of interest. Both parts will consists of a dose escalation portion and a dose expansion portion.
Interventions
DRUGATX-898
Doses defined per protocol
DRUGATX-898, fulvestrant, ribociclib
ATX-898 at RDE, Fulvestrant and abemaciclib: doses defined per protocol
Sponsors
Antares Therapeutics, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically or cytologically confirmed advanced solid tumor malignancy that is metastatic or locally advanced and unresectable * Is ≥18 years of age at the time of signing the informed consent form * ECOG performance status score of 0 or 1 * Adequate organ function * Must consent to a pre-treatment tumor biopsy (collected during screening or have available archival tumor tissue in the past 5 years. For Part 1a (monotherapy dose escalation) * Has received one or more standard systemic therapies and additional standard therapies are either not available, or participant ineligible for available standard therapies For Part 1b (monotherapy dose expansion) * b1: Has platinum-resistant or refractory metastatic ovarian cancer * b2: Has recurrent or metastatic gynecologic cancer excluding the cancers eligible for b1 * b3: Has recurrent advanced or metastatic solid tumor excluding the cancers eligible for b1 or b2 * Has at least 1 measurable lesion per RECIST 1.1 For Part 2a (combination dose escalation) * Has confirmed HR+ HER2 - (including HER2 low and ultra low) status * Has received prior therapy in the metastatic For Part 2b (combination dose expansion) * Has confirmed HR+ HER2 - (including HER2 low and ultra low) status * Treatment-naïve or has received prior therapy in the metastatic setting
Exclusion criteria
* Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancer being studied * Has symptomatic CNS metastases at screening or asymptomatic CNS metastases requiring corticosteroids to control symptoms within 28 days prior to the first dose of ATX-898. * Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, with the exception of alopecia any grade and Grade ≤2 peripheral neuropathy * Has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant or would prevent, limit, or confound the protocol-specified assessments Cohort Specific: * For abemaciclib cohorts only: has a history of any events of cardiac etiology that would contraindicate dosing with abemaciclib * For ribocicilib only: has history of pneumonitis or interstitial lung disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1a monotherapy dose escalation - Maximally tolerated/tested dose (MTD) | 12 months | Maximum dose deemed safe and well tolerated during dose escalation |
| Part 1a monotherapy dose escalation - Recommended dose for expansion (RDE) | 12 months | Monotherapy dose recommended to test during dose expansion |
| Part 1a monotherapy dose escalation - Treatment emergent adverse events (TEAEs) | 12 months | Any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug. |
| Part 1b monotherapy dose expansion - Objective Response Rate (ORR) | 24 months | Percentage of participants with confirmed CR or PR per RECIST 1.1 |
| Part 2a combination dose escalation - Occurrence of Dose limiting toxicities (DLTs) | 18 months | Toxicities occurring within the first treatment cycle of combination therapy (28 days). DLTs will be assessed in severity by the investigators per CTCAE v 6.0 |
| Part 2a combination dose escalation - Maximally tolerated/tested dose (MTD) | 18 months | Maximum dose deemed safe and well tolerated during dose escalation of with combination treatment |
| Part 2a combination dose escalation - Recommended dose for expansion (RDE) | 18 months | Recommended dose for expansion (RDE) Monotherapy dose recommended to test during dose expansion of combination treatment 18 months |
| Part 2a combination dose escalation - Treatment emergent adverse events (TEAEs) | 18 months | Any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug. 18 months |
| Part 2b combination dose expansion - Objective Response Rate (ORR) | 36 months | Percentage of participants with confirmed CR or PR per RECIST 1.1 |
| Part 1a monotherapy dose escalation - Occurrence of Dose limiting toxicities (DLTs) | 12 months | Toxicities occurring within the first treatment cycle (28 days). DLTs will be assessed in severity by the investigators per CTCAE v 6.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2b combination dose expansion - Treatment emergent adverse events (TEAEs) | 36 months | Any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug when given in combination |
| Part 2b monotherapy dose expansion - Pharmacokinetic assessment Cmax | 12 months | Cmax of ATX-898 following treatment at RDE when given in combination |
| Part 2b monotherapy dose escalation - Pharmacokinetic assessment Tmax | 12 Months | Time it takes for the study drug to reach peak concentration (Cmax) in the blood following treatment at RDE when given in combination |
| Part 2b monotherapy dose escalation - Pharmacokinetic assessment AUC | 12 Months | Area under the conc-time curve exposure of the study drug following treatment at RDE when given in combination |
| Part 2b monotherapy dose escalation - Pharmacokinetic assessment T 1/2 | 12 Months | Time required for the concentration of study drug in the body to reduce by half following treatment at RDE when given in combination |
| Part 2b monotherapy dose escalation - Pharmacokinetic assessment Ctrough | 12 Months | Lowest measured concentration of study drug in the blood right before the next scheduled dose at RDE when given in combination |
| Part 1a monotherapy dose escalation - Pharmacokinetic assessment Tmax | 12 Months | Time it takes for the study drug to reach peak concentration (Cmax) in the blood following treatment |
| Part 1a monotherapy dose escalation - Pharmacokinetic assessment AUC | 12 Months | Area under the conc-time curve exposure of the study drug following treatment |
| Part 1a monotherapy dose escalation - Pharmacokinetic assessment T 1/2 | 12 Months | Time required for the concentration of study drug in the body to reduce by half following treatment |
| Part 1a monotherapy dose escalation - Pharmacokinetic assessment Ctrough | 12 Months | Lowest measured concentration of study drug in the blood right before the next scheduled dose |
| Part 1a monotherapy dose escalation - Objective Response Rate (ORR) | 12 months | Percentage of participants with confirmed CR or PR per RECIST 1.1 |
| Part 1b monotherapy dose expansion - Treatment emergent adverse events (TEAEs) | 24 Months | Any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug |
| Part 1b monotherapy dose expansion - Pharmacokinetic assessment Cmax | 12 months | Cmax of ATX-898 following treatment at RDE |
| Part 1b monotherapy dose escalation - Pharmacokinetic assessment Tmax | 12 Months | Time it takes for the study drug to reach peak concentration (Cmax) in the blood following treatment at RDE |
| Part 1a monotherapy dose escalation - Pharmacokinetic assessment Cmax | 12 months | Cmax of ATX-898 following treatment |
| Part 1b monotherapy dose escalation - Pharmacokinetic assessment AUC | 12 Months | Area under the conc-time curve exposure of the study drug following treatment at RDE |
| Part 1b monotherapy dose escalation - Pharmacokinetic assessment T 1/2 | 12 Months | Time required for the concentration of study drug in the body to reduce by half following treatment at RDE |
| Part 1b monotherapy dose escalation - Pharmacokinetic assessment Ctrough | 12 Months | Lowest measured concentration of study drug in the blood right before the next scheduled dose at RDE |
| Part 2a combination dose escalation - Objective Response Rate (ORR) | 18 months | Percentage of participants with confirmed CR or PR per RECIST 1.1 |
| Part 2a monotherapy dose expansion - Pharmacokinetic assessment Cmax | 12 months | Cmax of ATX-898 following treatment |
| Part 2a monotherapy dose escalation - Pharmacokinetic assessment Tmax | 12 Months | Time it takes for the study drug to reach peak concentration (Cmax) in the blood following treatment |
| Part 2a monotherapy dose escalation - Pharmacokinetic assessment AUC | 12 Months | Area under the conc-time curve exposure of the study drug following treatment |
| Part 2a monotherapy dose escalation - Pharmacokinetic assessment T 1/2 | 12 Months | Time required for the concentration of study drug in the body to reduce by half following treatment |
| Part 2a monotherapy dose escalation - Pharmacokinetic assessment Ctrough | 12 Months | Lowest measured concentration of study drug in the blood right before the next scheduled dose |
Contacts
CONTACTFor questions concerning enrollment
Outcome results
None listed