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History of Changes for Study: NCT04053673
RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors , FIH, MAD Study
Latest version (submitted March 27, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 9, 2019 None (earliest Version on record)
2 January 16, 2020 Contacts/Locations and Study Status
3 March 23, 2020 Study Status and Contacts/Locations
4 January 27, 2021 Study Status and Study Design
5 May 5, 2021 Contacts/Locations and Study Status
6 July 19, 2021 Study Status and Contacts/Locations
7 August 25, 2021 Contacts/Locations and Study Status
8 October 20, 2021 Contacts/Locations, Study Design and Study Status
9 November 18, 2021 Outcome Measures, Study Status, References, Eligibility, Study Design, Study Description and Study Identification
10 December 16, 2021 Study Status and Contacts/Locations
11 July 5, 2022 Contacts/Locations and Study Status
12 March 27, 2023 Study Status
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Study NCT04053673
Submitted Date:  August 9, 2019 (v1)
Open or close this module Study Identification
Unique Protocol ID: RBN-2397-19-001
Brief Title: RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors , FIH, MAD Study
Official Title: 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
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2019
Overall Status: Recruiting
Study Start: August 1, 2019
Primary Completion: December 31, 2020 [Anticipated]
Study Completion: January 31, 2021 [Anticipated]
First Submitted: August 5, 2019
First Submitted that
Met QC Criteria:		 August 9, 2019
First Posted: August 12, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:		 August 9, 2019
Last Update Posted: August 12, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Ribon Therapeutics, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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.
Detailed Description:

This is a first-in-human, Phase 1, multi-center, open-label, dose-escalation study to:

  • Evaluate the safety profile and MTD of RBN-2397 administered orally and establish the RBN-2397 dose(s) and schedule(s) recommended for further investigation in Phase 2
  • Characterize the PK profile of RBN-2397
  • Identify preliminary antitumor activity.
  • Biomarkers and their correlation with response to RBN-2397 and other outcomes will be examined.

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.

After the MTD is determined, Expansion Cohort(s) of approximately 20 participants each will be enrolled to further examine the safety, PK, pharmacodynamics, and antitumor activity of RBN-2397 at the MTD or other dose recommended for further investigation. Based on nonclinical data as well as clinical data obtained from the dose-escalation portion of this study, enrollment in the Expansion Cohort(s) may be limited to specific tumor type(s), as warranted by the data.
Open or close this module Conditions
Conditions: Solid Tumor, Adult
Keywords: Phase 1
PARP7 inhibition
First in Human
Solid Tumors
Interferon
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Dose Escalation
Number of Arms: 1
Masking: None (Open Label)
Enrollment: 120 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
 Drug: RBN-2397
an oral PARP7 Inhibitor
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
[ Time Frame: through study completion (an average of one year) ]

Frequency of Dose limiting Toxicities (DLTs)
2. Safety and tolerability
[ Time Frame: through study completion (an average of one year) ]

Grade and frequency of adverse events and serious adverse events
Secondary Outcome Measures:
1. Area under the plasma concentration
[ Time Frame: Through Study Day 22 ]

Area-under-the-curve (AUC inf)
2. Peak plasma concentration
[ Time Frame: Through Study Day 22 ]

Cmax
3. Antitumor activity that may be associated with RBN-2397 treatment assessed by CT/MRI Response Evaluation Criteria for Solid Tumors (RECIST) Criteria v1.1
[ Time Frame: Every 6-8 weeks; through study completion (an average of one year) ]

Objective response rate (ORR)
4. Antitumor activity that may be associated with RBN-2397 treatment
[ Time Frame: Every 6-8 weeks; through study completion (an average of one year) ]

Disease control rate (DCR)
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • 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.
  • Male or female aged ≥18 years.
  • 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:

  • Unable to swallow oral medications
  • Major surgery within 4 weeks of starting study
  • Pregnant or breast-feeding.
  • Receiving intravenous antibiotics for an active infection
  • Known human immunodeficiency virus (HIV) or hepatitis B or C infection.
  • History of a different malignancy unless disease-free for at least 5 years
  • Some medications are not allowed while on study. Interested participants will need to inform study doctor of all the medications he/she is taking.
  • Herbal medicines, and grapefruit, grapefruit juice, pomegranate juice, star fruit or orange marmalade (made with Seville oranges) are not allowed to be taken during study.
Open or close this module Contacts/Locations
Central Contact Person: Sudha Parasuraman, MD
Telephone: 617-914-8700
Email: sparasuraman@ribontx.com
Central Contact Backup: Kristy Kuplast-Barr, BS
Telephone: 617 914 8594
Email: kkuplastbarr@ribontx.com
Study Officials: Melissa L Johnson, MD
Principal Investigator
Tennessee Oncology, PLLC
Locations: United States, Colorado
SCRI-Denver/HealthOne
[Recruiting]
Denver, Colorado, United States, 80218
Contact:Contact: Gerald Falchook, MD 281-221-0693 Gerald.Falchook@SarahCannon.com
Contact:Principal Investigator: Gerald Falchook, MD
United States, Florida
SCRI-Sarasota/Florida Cancer Specialists
[Recruiting]
Sarasota, Florida, United States, 34232
Contact:Contact: Manish Patel, MD 941-377-9993 mpatel@flcancer.com
Contact:Principal Investigator: Manish Patel, MD
United States, Tennessee
SCRI-Nashville/Tennessee Oncology
[Recruiting]
Nashville, Tennessee, United States, 37203
Contact:Contact: Melissa Johnson, MD 615-329-7274 mjohnson@tnonc.com
Contact:Principal Investigator: Melissa L. Johnson, MD
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations: Cohen MS, Chang P. Insights into the biogenesis, function, and regulation of ADP-ribosylation. Nat Chem Biol. 2018 Feb 14;14(3):236-243. doi: 10.1038/nchembio.2568. PubMed 29443986
Links:
Available IPD/Information:
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