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RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors , FIH, MAD Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04053673
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Information provided by (Responsible Party):
Ribon Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE August 5, 2019
First Posted Date  ICMJE August 12, 2019
Last Update Posted Date August 12, 2019
Actual Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2019)
  • 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)
  • Safety and tolerability [ Time Frame: through study completion (an average of one year) ]
    Grade and frequency of adverse events and serious adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2019)
  • Area under the plasma concentration [ Time Frame: Through Study Day 22 ]
    Area-under-the-curve (AUC inf)
  • Peak plasma concentration [ Time Frame: Through Study Day 22 ]
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors , FIH, MAD Study
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Intervention Model Description:
Dose Escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor, Adult
Intervention  ICMJE Drug: RBN-2397
an oral PARP7 Inhibitor
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
Publications * 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. Review.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 9, 2019)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sudha Parasuraman, MD 617-914-8700
Contact: Kristy Kuplast-Barr, BS 617 914 8594
Listed Location Countries  ICMJE United States
Removed Location Countries  
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
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ribon Therapeutics, Inc.
Study Sponsor  ICMJE Ribon Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Melissa L Johnson, MD Tennessee Oncology, PLLC
PRS Account Ribon Therapeutics, Inc.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP