Phase 1 Study of RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors
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ClinicalTrials.gov Identifier: NCT04053673 |
Recruitment Status :
Recruiting
First Posted : August 12, 2019
Last Update Posted : March 28, 2023
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Tracking Information | |||||
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First Submitted Date ICMJE | August 5, 2019 | ||||
First Posted Date ICMJE | August 12, 2019 | ||||
Last Update Posted Date | March 28, 2023 | ||||
Actual Study Start Date ICMJE | August 1, 2019 | ||||
Estimated Primary Completion Date | June 30, 2023 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [ Time Frame: through first treatment cycle (an average of 21 days) ] Incidence of Dose limiting Toxicities (DLTs)
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Original Primary Outcome Measures ICMJE |
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Phase 1 Study of RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors | ||||
Official Title ICMJE | A Phase 1, First-in-human Study of the Safety, Single- and Multiple-Dose Pharmacokinetics, and Preliminary Activity of Escalating Doses of RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors | ||||
Brief Summary | RBN-2397 inhibits PARP7, an enzyme that is switched on by cancer stresses, such as the toxins in cigarette smoke. Cancer cells use PARP7 to hide from the immune system by stopping the cell from sending a signal (Type 1 interferon) that tells the immune system that something is wrong and to kill the cell. RBN-2397 has been shown in animal studies to inhibit tumor growth and also shuts down the "don't kill me" signal the tumor is sending to evade the immune system. As a PARP7 inhibitor RBN-2397 is different from drugs inhibiting PARP1, PARP2 and PARP3 enzymes which are approved for the treatment of certain ovarian and breast cancers. The primary purpose of this study is to determine the maximum tolerated dose (MTD) of orally administered RBN-2397 in patients with advanced or metastatic solid tumors. This study will also evaluate the safety and tolerability of RBN-2397, examine the pharmacokinetics (PK) (measure how the body absorbs, breaks down and eliminates RBN-2397) and investigate whether it has antitumor activity in solid tumor cancers. |
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Detailed Description | This is a first-in-human, Phase 1, multi-center, open-label, dose-escalation study to:
Cohorts will follow a traditional 3 + 3 design. After enrollment of the first participant within a cohort, there must be a wait period of at least 1 week before enrollment of additional participants in that cohort. This dose escalation phase of the study is complete. The study is currently in the Relative Bioavailability and Expansion Cohort(s) phase where approximately 20 participants each will be enrolled to further examine the safety, PK, pharmacodynamics, and antitumor activity of RBN-2397 at the recommended phase 2 dose. Relative Bioavailability Assessment: An evaluation of relative bioavailability of a micronized RBN-2397 tablet versus the standard RBN-2397 tablet (manufactured with unmicronized RBN-2397 and used in the dose escalation phase of the study) will be performed as part of the dose escalation phase. Micronized tablets will be used in the Dose Expansion Phase of the study after the relative bioavailability assessment has been completed. Dose Expansion Phase The recommended phase 2 dose will be investigated in the following cancer types: squamous cell carcinoma of the lung (SCCL), head and neck squamous cell carcinoma (HNSCC), hormone receptor positive (HR+) breast cancer, and PARP7 amplified cancer. Duration of treatment: It is anticipated that the minimum study involvement will be one cycle. Participants are eligible to have an indefinite number of additional cycles of treatment if their disease does not progress and they do not have unacceptable side effects. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Sequential Assignment Intervention Model Description: Dose Expansion Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE | Solid Tumor, Adult | ||||
Intervention ICMJE | Drug: RBN-2397
an oral PARP7 Inhibitor
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Study Arms ICMJE | Experimental: RBN-2397
Dose Escalation: Multiple doses of RBN-2397 for oral administration Dose Expansion: Oral dose of RBN-2397 as determined during Dose Escalation
Intervention: Drug: RBN-2397
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
130 | ||||
Original Estimated Enrollment ICMJE |
120 | ||||
Estimated Study Completion Date ICMJE | July 31, 2023 | ||||
Estimated Primary Completion Date | June 30, 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria: Dose Escalation Phase only: Metastatic or advanced-stage solid malignant tumor (which may include "solid" lymphoma [e.g., mantle cell]) for whom no therapy exists that would be curative or might provide clinical benefit. Dose Expansion Phase Only: Patients with locally advanced or metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have received standard therapy or are intolerant of standard therapy, have progressed following their last prior therapy, and have one of the following tumor types:
Must agree to undergo tumor biopsy Normal organ and bone marrow function Patient and his/her partner agree to use adequate contraception during and for 3 months after the last study drug dose Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Spain, United States | ||||
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Administrative Information | |||||
NCT Number ICMJE | NCT04053673 | ||||
Other Study ID Numbers ICMJE | RBN-2397-19-001 | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Ribon Therapeutics, Inc. | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Ribon Therapeutics, Inc. | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Ribon Therapeutics, Inc. | ||||
Verification Date | July 2022 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |