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

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ClinicalTrials.gov Identifier: NCT04053673
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Ribon Therapeutics, Inc.

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.


Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: RBN-2397 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : January 31, 2021

Arm Intervention/treatment
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




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)



Information from the National Library of Medicine

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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:

  • 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.

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): NCT04053673


Contacts
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Contact: Sudha Parasuraman, MD 617-914-8700 sparasuraman@ribontx.com
Contact: Kristy Kuplast-Barr, BS 617 914 8594 kkuplastbarr@ribontx.com

Locations
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United States, Colorado
SCRI-Denver/HealthOne Recruiting
Denver, Colorado, United States, 80218
Contact: Gerald Falchook, MD    281-221-0693    Gerald.Falchook@SarahCannon.com   
Principal Investigator: Gerald Falchook, MD         
United States, Florida
SCRI-Sarasota/Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Manish Patel, MD    941-377-9993    mpatel@flcancer.com   
Principal Investigator: Manish Patel, MD         
United States, Tennessee
SCRI-Nashville/Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Melissa Johnson, MD    615-329-7274    mjohnson@tnonc.com   
Principal Investigator: Melissa L. Johnson, MD         
Sponsors and Collaborators
Ribon Therapeutics, Inc.
Investigators
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Principal Investigator: Melissa L Johnson, MD Tennessee Oncology, PLLC

Publications:
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Responsible Party: Ribon Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04053673     History of Changes
Other Study ID Numbers: RBN-2397-19-001
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ribon Therapeutics, Inc.:
Phase 1
PARP7 inhibition
First in Human
Solid Tumors
Interferon
Additional relevant MeSH terms:
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Neoplasms