Advanced Solid Tumor, Homologous Recombination Deficiency, HRR Deficiency
Conditions
Brief summary
This trial investigates a new drug, EIS-12656, in participants with specified advanced solid tumors carrying pre-specified mutations. The trial consists of a dose escalation part (Phase 1) and a dose expansion part (Phase 2).
Detailed description
The trial is a Phase 1/2, open label, uncontrolled trial to investigate the safety and preliminary efficacy of EIS-12656 alone or in combination with a PARPi or T-DXd in patients with specified advanced or metastatic solid tumors with homologous recombination deficient (HRD) mutations. In the Phase 1 dose escalation phase participants will receive ascending doses of EIS-12656 to evaluate the safety and tolerability and to determine an effective and safe dose for the Phase 2 part. In the Phase 2 dose expansion phase participants will either receive EIS-12656 monotherapy at the recommended Phase 2 dose (RP2D) (Module 1) or EIS-12656 in combination with a PARPi or T-DXd (Modules 2 and 3). The objective is to evaluate the safety and tolerability and anti-tumor activity of EIS-12656 alone or in combination.
Interventions
DRUGEIS-12656
EIS-12656 tablets given daily
DRUGOlaparib
as per USPI/SmPC
DRUGTrastuzumab deruxtecan
as per USPI/SmPC
Sponsors
Eisbach Bio GmbH
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
* Recurrent locally advanced or metastatic solid tumors * Homologous recombination deficient mutations * Progressed on at least on prior line of treatment or intolerant to additional effective standard therapy * Measurable disease (RECIST 1.1 Criteria) * Adequate organ and bone marrow function * ECOG Performance Status 0 or 1 * Life expectancy \> 3 months
Exclusion criteria
* History or evidence of any clinically relevant gastrointestinal disease * Radiation therapy within ≤2 weeks * Significant cardiovascular disease * Uncontrolled, active, symptomatic brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and percentage of participants experiencing a dose limiting toxicity (DLT) (dose escalation part only) | Within 21 days of first dose | A DLT is defined as an EIS-12656 related adverse event during the first treatment cycle that meets the criteria outlined in the study protocol |
| Number and percentage of participants experiencing treatment-emergent adverse events (TEAEs) | From screening until end of treatment follow-up (45 days after last dose) (up to 7 months) | Number and percentage of participants with adverse events, serious adverse events, adverse events of special interest including changes in safety lab parameters, physical examinations, vital signs, and electrocardiogram (ECG) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration of EIS-12656 (Cmax) | At pre-defined intervals from pre-dose Day 1 to Day 29 | The concentration of EIS-12656 in plasma will be determined (Cmax will be derived) |
| Area under the curve (AUC0-24) | At pre-defined intervals from pre-dose Day 1 to Day 29 | The AUC0-24 reflects the actual body exposure to drug over the last 24h dosing interval |
| Time to maximum concentration (Tmax) | At pre-defined intervals from pre-dose Day 1 to Day 29 | The concentration of EIS-12656 in plasma will be determined (Tmax will be derived) |
| Overall Response Rate | From screening to disease progression (approximately 1 year) | Overall response rate defined as percentage of participants with the best overall response of confirmed CR or confirmed PR according to RECIST v1.1 |
| Duration of Response | From screening to disease progression or death (approximately 1 year) | Time from first response to progression or death, as defined by RECIST 1.1 |
| Progression Free Survival | From screening to disease progression or death (approximately 1 year) | Time from first dose of EIS-12656 to progression or death, as defined by RECIST 1.1 |
Countries
United States
Contacts
Primary ContactAdrian Schomburg
Outcome results
None listed