Trial record 1 of 1 for:
PRT3789-01
PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation
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| ClinicalTrials.gov Identifier: NCT05639751 |
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Recruitment Status :
Recruiting
First Posted : December 6, 2022
Last Update Posted : April 29, 2024
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Sponsor:
Prelude Therapeutics
Information provided by (Responsible Party):
Prelude Therapeutics
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Brief Summary:
This is a Phase 1 dose-escalation study of PRT3789, a SMARCA2 degrader, in participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of PRT3789 monotherapy and in combination with docetaxel, describe any dose limiting toxicities (DLTs), define the dosing schedule, and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) to be used in subsequent development of PRT3789.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Solid Tumor Metastatic Solid Tumor Non-small Cell Lung Cancers SMARCA4 Gene Mutation | Drug: PRT3789 Drug: Docetaxel | Phase 1 |
This is an open-label, multi-center, dose-escalation, first in human, Phase 1 study of PRT3789 as monotherapy and in combination with docetaxel, a SMARCA2 degrader, evaluating participants with advanced or metastatic solid tumors with loss of SMARCA4 due to truncating mutation and/or deletion. The study will evaluate escalating doses of PRT3789 until the MTD or RP2D is determined. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Approximately 118 participants will be enrolled in monotherapy, dose escalation, backfill, and combination cohorts.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 118 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 as Monotherapy and in Combination With Docetaxel in Participants With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation |
| Actual Study Start Date : | May 2, 2023 |
| Estimated Primary Completion Date : | March 2026 |
| Estimated Study Completion Date : | March 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
Drug Information
available for:
Docetaxel
| Arm | Intervention/treatment |
|---|---|
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Experimental: PRT3789 Monotherapy
PRT3789 will be administered by intravenous infusion
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Drug: PRT3789
PRT3789 will be administered by intravenous infusion |
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Experimental: PRT3789/Docetaxel Combination
PRT3789 and Docetaxel will be administered by intravenous infusions
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Drug: PRT3789
PRT3789 will be administered by intravenous infusion Drug: Docetaxel Docetaxel will be administered by intravenous infusion |
Primary Outcome Measures :
- Dose limiting toxicity (DLT) of PRT3789 monotherapy and in combination with docetaxel [ Time Frame: Baseline through Day 21 ]Dose limiting toxicities will be evaluated over the 21-day observation period
- Safety and tolerability of PRT3789 monotherapy and in combination with docetaxel: AEs, CTCAE Assessments [ Time Frame: Baseline through approximately 3 years ]Safety and tolerability will be evaluated by incidence of DLTs, laboratory measurements, dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
- Maximum tolerated dose (MTD)/ Recommended phase 2 dose (RP2D) of PRT3789 monotherapy and in combination with docetaxel [ Time Frame: Baseline through approximately 3 years ]The MTD/RP2D will be established for further investigation in participants with advanced solid tumors
Secondary Outcome Measures :
- Efficacy of PRT3789 monotherapy and in combination with docetaxel: Objective response rate (ORR) [ Time Frame: Baseline through approximately 3 years ]Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator per RECIST v1.1
- Efficacy of PRT3789 monotherapy and in combination with docetaxel: Progression-free survival (PFS) [ Time Frame: Baseline through approximately 3 years ]Duration from Day 1 to the earliest date of first disease progression, as assessed by the investigator per RECIST v1.1, discontinuation because of disease progression, or death due to any cause
- Efficacy of PRT3789 monotherapy and in combination with docetaxel: Clinical benefit rate (CBR) [ Time Frame: Baseline through approximately 3 years ]Best overall response of CR, PR, or durable stable disease (24 weeks or longer duration), as assessed by the investigator per RECIST v1.1
- Efficacy of PRT3789 monotherapy and in combination with docetaxel: Duration of response (DOR) [ Time Frame: Baseline through approximately 3 years ]Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator per RECIST v1.1, or death due to any cause
- Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Maximum observed plasma concentration [ Time Frame: Baseline through approximately 3 years ]Pharmacokinetics will be calculated including the maximum observed plasma concentration
- Pharmacokinetic profile of PRT3789 monotherapy and in combination with docetaxel: Area under the curve [ Time Frame: Baseline through approximately 3 years ]Pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
- Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel: Target engagement [ Time Frame: Baseline through approximately 3 years ]Pharmacodynamic effect of PRT3789 monotherapy and in combination with docetaxel demonstrating target engagement by assessment of SMARCA2 protein in peripheral blood mononuclear cells (PBMCs) and tumor tissue
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures
- Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy with any mutation of SMARCA4 (dose escalation and combination cohorts) and loss of function mutation of SMARCA4 (backfill cohorts) by local testing that have either progress on or ineligible for standard of care therapy
- Must have measurable or non-measureable (but evaluable) disease per RECIST v1.1 for dose escalation and combination cohorts
- Must have measureable diseases per RECIST v1.1 for backfill cohort
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Willing to provide either archival or fresh tumor tissue sample
- Adequate organ function (hematology, renal, and hepatic)
Exclusion Criteria:
- Participants with solid tumors with known concomitant SMARCA2 mutation or loss of protein expression
- Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease
- History of another malignancy within 3 years except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancies, or malignancies previously treated with curative intent and not on active therapy or expected to require treatment or recurrence during the study
- Concurrent treatment with strong or moderate CYP3A4 inhibitor or inducer
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05639751
Contacts
| Contact: Study Contact (Please Do Not Disclose Personal Information) | See Email | clinicaltrials@preludetx.com |
Locations
Show 25 study locations
Sponsors and Collaborators
Prelude Therapeutics
| Responsible Party: | Prelude Therapeutics |
| ClinicalTrials.gov Identifier: | NCT05639751 |
| Other Study ID Numbers: |
PRT3789-01 |
| First Posted: | December 6, 2022 Key Record Dates |
| Last Update Posted: | April 29, 2024 |
| Last Verified: | April 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Prelude Therapeutics:
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Advanced Solid Tumors BRG1 BRM Metastatic Solid Tumors Non-Small Cell Lung Cancers |
NSCLC PRT3789 SMARCA2 Degrader SMARCA4 Docetaxel |
Additional relevant MeSH terms:
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Neoplasms Carcinoma, Non-Small-Cell Lung Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Docetaxel Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |