ER+, HER 2- Breast Cancer, Non-small Cell Lung Cancer (NSCLC), Castration-resistant Prostate Cancer (CRPC), Microsatellite Stable (MSS) Colorectal Carcinoma
Conditions
Keywords
ER+, HER 2- Breast Cancer, Non-small Cell Lung Cancer (NSCLC), Castration-resistant Prostate Cancer (CRPC), Microsatellite Stable (MSS) Colorectal Carcinoma, KAT6A/B, KAT7
Brief summary
IDE574 is a synthetically manufactured small molecule inhibitor that co-targets the lysine acetyltransferase enzymes KAT6 and KAT7. The purpose of this study is to evaluate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of IDE574 as monotherapy in participants with locally advanced or metastatic solid tumors and as combination therapy with fulvestrant in participants with advanced or metastatic ER+, HER2- breast cancer.
Detailed description
Part 1 - Monotherapy Dose Escalation and Expansion: Part 1A - Monotherapy Dose Escalation Part 1A will evaluate increasing doses of IDE574 to assess safety, tolerability and to determine dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) or the recommended dose for expansion (RDE) in subjects with advanced or metastatic ER+, HER2- breast cancer, non-small cell lung cancer, castration-resistant prostate cancer and microsatellite-stable colorectal cancer. Part 1B - Monotherapy Dose Expansion Part 1B will evaluate in ER+ HER2- advanced or metastatic breast cancer at the potential dose level(s) determined to be safe and tolerable during monotherapy dose escalation Part 1A. In parallel, a basket cohort may be enrolled at or below the highest safe dose level(s) determined to be safe and tolerable in Part 1A. Part 2 - Combination Dose Escalation and Expansion Part 2A - IDE574 Combination Therapy with Fulvestrant Dose Escalation Part 2A will evaluate participants with ER+ HER2- advanced or metastatic breast cancer with escalating doses of IDE574 in combination with fulvestrant to assess safety, tolerability and to determine DLTs, MTD or RDE. Part 2B - IDE574 Combination Therapy with Fulvestrant Dose Expansion Part 2B will be evaluated in ER+ HER2- advanced or metastatic breast cancer at the potential dose level(s) determined to be safe and tolerable during combination dose escalation Part 2A.
Interventions
DRUGIDE574
IDE574
Fulvestrant Injection
Sponsors
IDEAYA Biosciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Archival Tissue sample for testing * Part 1A - Participants with advanced or metastatic ER+, HER2- breast cancer, NSCLC, CRPC, and MSS colorectal adenocarcinoma who have progressed on/after at least one line of standard of care therapy or are intolerant to additional effective therapies. * Parts 1B, 2A and 2B: Participants with ER+, HER2- breast cancer who have progressed after at least 1 prior line of treatment with an endocrine therapy and a CDK4/6 inhibitor * Female participants with ER+, HER2- breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause (Parts 2A and B only) * Female participants of nonchildbearing potential with ER+, HER2- breast cancer must meet at least 1 of the following criteria: Age ≥ 60 years or age \<60 years with absence of menstruation for at least 12 months, or had prior removal of both ovaries * Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1. * Have adequate bone marrow, renal and liver function. * Life expectancy of \>3 months * Able to safely administer and retain orally administered study treatment * Able to comply with contraceptive/barrier requirements Key
Exclusion criteria
* Known symptomatic brain metastases or leptomeningeal metastasis * Known primary CNS malignancy and any other malignancies within 2 years prior to the first dose with the exception of adequately treated localized tumor. * Have impairment of GI function or GI disease that may significantly alter the absorption of IDE574. * Have active liver or biliary disease. * Have active, uncontrolled bacterial, fungal, or viral infection * Have clinically significant cardiac abnormalities and/or blood clotting events within 6 months before the first dose * If participants had adverse reactions to previous experimental antitumor treatment that have not recovered to Grade ≤ 1 * Prior irradiation to \>25% of the bone marrow. * Known or suspected hypersensitivity to IDE574/excipients or components (Parts 1 \& 2) or fulvestrant/excipients or components (Part 2 only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of IDE574 in Part 1 A Monotherapy Dose escalation | 21 days following the first dose of IDE574 | incidence of DLT; incidence and severity of AEs/serious adverse events (SAEs) graded based on CTCAE V6.0 |
| Safety and Tolerability of IDE574 in Part 1B Monotherapy Dose expansion based on incidence and severity of AEs/SAEs | Approximately 24 months total study duration | Incidence and severity of AEs/SAEs graded based on CTCAE V6.0 |
| To evaluate anti-tumor activity of IDE574 of IDE574 in Part 1B Monotherapy Dose expansion based on the ORR per RECIST version 1.1 | Approximately 24 months total study duration | Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
| To evaluate anti-tumor activity of IDE574 of IDE574 in Part 1B Monotherapy Dose expansion based on DOR per RECIST version 1.1. | Approximately 24 months total study duration | Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
| Safety and tolerability of IDE574 in combination with Fulvestrant in Part 2A Combination Dose Escalation based on incidence of DLT | Approximately 24 months total study duration | Incidence of DLT; incidence and severity of AEs/SAEs graded based on CTCAE V6.0 |
| Safety and tolerability of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on the incidence and severity of AEs/SAEs | Approximately 24 months total study duration | Incidence and severity of AEs/SAEs graded based on CTCAE V6.0 |
| Anti-tumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on the ORR per RECIST version 1.1 | Time Frame: Approximately 24 months total study duration | Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
| Anti-tumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on DOR per RECIST version 1.1. | Time Frame: Approximately 24 months total study duration | Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on the ORR per RECIST version 1.1 | Approximately 24 months total study duration | Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
| Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on DOR per RECIST version 1.1. | Approximately 24 months total study duration | Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
| Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on Clinical Benefit Rate (CBR) | Approximately 24 months total study duration | CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose. |
| Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on Disease control rate | Approximately 24 months total study duration | Disease Control Rate (DCR) is the proportion of participants with a BOR of CR, PR, and SD lasting for at least 6 weeks (± 7 days) from the first dose per RECIST version 1.1 |
| Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation | Approximately 24 months total study duration | Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast) |
| Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion | Approximately 24 months total study duration | Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast) |
| Evaluate antitumor activity of IDE574 in Part 1B Monotherapy Dose Expansion based on CBR for ER+, HER2- breast cancer | Approximately 24 months total study duration | CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose |
| Evaluate antitumor activity of IDE574 in Part 1B Monotherapy Dose Expansion based on DCR for other solid tumor types | Approximately 24 months total study duration | Disease Control Rate (DCR) is the proportion of participants with a BOR of CR, PR, and SD lasting for at least 6 weeks (± 7 days) from the first dose per RECIST version 1.1 |
| Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on ORR per RECIST version 1.1 | Approximately 24 months total study duration | Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
| Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on DOR per RECIST version 1.1 | Approximately 24 months total study duration | uration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response |
| Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on CBR per RECIST version 1.1 | Approximately 24 months total study duration | CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose. |
| Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation | Approximately 24 months total study duration | Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast) |
| Evaluate antitumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on CBR per RECIST version 1.1 | Approximately 24 months total study duration | CBR will be assessed based on the proportion of participants with a Best Overall Response (BOR) of CR, PR or SD lasting for 24 weeks per RECIST version 1.1 from the first dose. |
| Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion | Approximately 24 months total study duration | Area under concentration time curve from time 0 to the last quantifiable concentration (AUClast) |
Countries
United States
Outcome results
None listed