A Phase 1/1b Study of PRT13722 in Participants With Advanced HR+/HER2- Breast Cancer
A Phase 1/1b, First-in-Human, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of PRT13722, a KAT6A Protein Degrader, as Monotherapy and in Combination With Endocrine and Targeted Therapy in Adults With Locally Advanced or Metastatic HR-Positive, HER2-Negative Breast Cancer
This first-in-human, open-label, multicenter study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PRT13722, an oral KAT6A protein degrader, in adults with locally advanced or metastatic Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. PRT13722 will be evaluated as monotherapy and in combination with fulvestrant, abemaciclib plus fulvestrant, or imlunestrant to determine recommended dose(s) for expansion (RDE) and evaluate preliminary clinical activity.
調査の概要
状態
詳細な説明
This is a first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of PRT13722, a selective oral KAT6A protein degrader, in adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer. The study will evaluate the safety, tolerability, dose-limiting toxicities, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PRT13722 administered as monotherapy and in combination with fulvestrant, abemaciclib plus fulvestrant, or imlunestrant to determine recommended dose(s) for expansion and evaluate preliminary clinical activity.
The study is conducted in three parts:
Part 1: Monotherapy dose escalation and backfill cohorts. Part 2: Combination dose-escalation cohorts with fulvestrant, abemaciclib plus fulvestrant, and imlunestrant.
Part 3: Combination dose-expansion cohorts to further evaluate safety and preliminary efficacy at the selected dose levels.
Up to approximately 240 participants are planned for enrollment across the three parts of the study.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Study Contact (Please Do Not Disclose Personal Information)
- 電話番号：See Email
- メール：clinicaltrials@preludetx.com
研究場所
-
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Ohio
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Maumee、Ohio、アメリカ、43537
- 募集
- Taylor Cancer Research Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures.
- histological or cytological diagnosis of locally advanced or metastatic HR-positive/HER2-negative breast cancer
- Disease progression following prior standard therapy and eligible for the assigned study cohort
- Measurable or evaluable disease per RECIST v1.1
- Willingness to provide tumor tissue for biomarker analyses
- Eastern Cooperative Oncology Group performance status of 0-1
- Negative serum or urine pregnancy test and agree to use highly effective contraception or maintain true abstinence.
- Adequate organ function and bone marrow reserves (hematology, renal, and hepatic)
Exclusion Criteria:
- Untreated, symptomatic, or unstable brain metastases
- Symptomatic visceral disease at risk of imminent life-threatening complications
- Uncontrolled infection or significant concurrent medical conditions
- Clinically significant cardiovascular disease or prolonged QT syndrome
- Pregnancy or breastfeeding
- Prior treatment with a KAT6-targeting agent
- Recent anticancer therapy, radiotherapy, or major surgery
- Use of prohibited concomitant medications, including strong CYP3A4 inhibitors or inducers, proton pump inhibitors, P-gp inhibitors or inducers, and breast cancer resistance protein inhibitors
- Participation in another interventional clinical study
- Any condition that would interfere with study participation or evaluation of study results
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：PRT13722 Monotherapy
Participants receive PRT13722 once daily as monotherapy. This arm includes dose-escalation (Part 1A) and backfill cohorts (Part 1B) evaluating PRT13722 in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer to support the selection of RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. |
|
実験的：PRT13722 + Fulvestrant
Participants receive PRT13722 once daily in combination with fulvestrant. This study includes a dose-escalation (Part 2A) in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer followed by dose-expansion (Part 3A) at the RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. Fulvestrant is an approved selective estrogen receptor degrader (SERD) administered on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, then once monthly as an intramuscular injection into the buttocks (gluteal muscle). |
|
実験的：PRT13722 + Abemaciclib + Fulvestrant
Participants receive PRT13722 once daily in combination with abemaciclib and fulvestrant. This study includes a dose-escalation (Part 2B) in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer followed by dose-expansion (Part 3B) at the RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. Fulvestrant is an approved selective estrogen receptor degrader (SERD) administered on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, then once monthly as an intramuscular injection into the buttocks (gluteal muscle). Abemaciclib is an approved oral cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor administered twice daily and used in combination with endocrine therapy for HR-positive, HER2-negative breast cancer. |
|
実験的：PRT13722 + Imlunestrant
Participants receive PRT13722 once daily in combination with imlunestrant. This study includes a dose-escalation (Part 2C) in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer followed by dose-expansion (Part 3C) at the RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. Imlunestrant is an approved oral SERD administered once daily. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Dose limiting toxicity of PRT13722 (Parts 1A and 2)
時間枠：Through cycle 1 (28 days)
|
Incidence of dose limiting toxicities, defined according to protocol-specified criteria |
Through cycle 1 (28 days)
|
|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of PRT13722 as monotherapy and in combination (Parts 1A and 2)
時間枠：Through study completion, an average of 2 years
|
Safety and tolerability assessed by the number of participants with treatment-emergent adverse events, serious adverse events, adverse events leading to dose modification, treatment interruption, or treatment discontinuation, and clinically significant laboratory abnormalities. Adverse events and selected laboratory abnormalities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 6.0 |
Through study completion, an average of 2 years
|
|
Preliminary Antitumor Activity: Objective Response Rate (Parts 1B and 3)
時間枠：Through study completion, an average of 2 years
|
Proportion of patients with best overall response of either complete response or partial response, as assessed by the investigator per RECIST v1.1 |
Through study completion, an average of 2 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Preliminary Antitumor Activity: Objective Response Rate (Parts 1A and 2)
時間枠：Through study completion, an average of 2 years
|
Proportion of patients with best overall response of either complete response or partial response, as assessed by the investigator per RECIST v1.1 |
Through study completion, an average of 2 years
|
|
Duration of Response
時間枠：Through study completion, an average of 2 years
|
Time from first documented response to disease progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first. |
Through study completion, an average of 2 years
|
|
Clinical Benefit Response
時間枠：Through study completion, an average of 2 years
|
Proportion of patients with a best overall response of complete response, partial response, or durable stable disease (24 weeks or longer), as assessed by the investigator per RECIST v1.1 |
Through study completion, an average of 2 years
|
|
Progression-Free Survival
時間枠：Through study completion, an average of 2 years
|
Time from the date of first dose of investigational product to the date of first documented disease progression, as assessed by the investigator per RECIST v1.1, or death due to any cause |
Through study completion, an average of 2 years
|
|
Overall Survival
時間枠：Through study completion, an average of 2 years
|
Time from the date of first dose of investigational product to death due to any cause |
Through study completion, an average of 2 years
|
|
Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] of PRT13722 as Monotherapy and in Combination (Parts 1B and 3)
時間枠：Through study completion, an average of 2 years
|
Safety and tolerability will be evaluated by incidence of adverse events leading to dose modifications, treatment interruptions, treatment discontinuations, and clinically significant laboratory abnormalities graded according to NCI CTCAE, Version 6.0 |
Through study completion, an average of 2 years
|
|
Maximum Observed Plasma Concentration (Cmax)
時間枠：Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
Maximum observed plasma concentration will be calculated using non-compartmental analysis |
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
|
Time To Maximum Concentration (Tmax)
時間枠：Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
Time to maximum concentration will be calculated using non-compartmental analysis |
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
|
Terminal Elimination Half-life (T1/2)
時間枠：Cycle 1 Day 1 (each cycle is 28 days)
|
Terminal elimination half-life will be calculated using non-compartmental analysis |
Cycle 1 Day 1 (each cycle is 28 days)
|
|
Area under the plasma concentration versus time curve (AUC)
時間枠：Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
Area under the plasma concentration-time curve will be calculated using non-compartmental analysis |
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
|
Steady State Trough Concentrations
時間枠：Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
Steady state trough concentrations will be calculated using non-compartmental analysis |
Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- PRT13722-01
- 2026-527825-37-00 (Ctis)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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