Clinical Trials /

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

NCT04053673

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: RBN-2397-19-001
  • NCT ID: NCT04053673

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
RBN-2397RBN-2397

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
RBN-2397ExperimentalDose Escalation: Multiple doses of RBN-2397 for oral administration Dose Expansion: Oral dose of RBN-2397 as determined during Dose Escalation
  • RBN-2397

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
Time Frame:through study completion (an average of one year)
Safety Issue:
Description:Frequency of Dose limiting Toxicities (DLTs)

Secondary Outcome Measures

Measure:Area under the plasma concentration
Time Frame:Through Study Day 22
Safety Issue:
Description:Area-under-the-curve (AUC inf)
Measure:Peak plasma concentration
Time Frame:Through Study Day 22
Safety Issue:
Description:Cmax
Measure: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)
Safety Issue:
Description:Objective response rate (ORR)
Measure:Antitumor activity that may be associated with RBN-2397 treatment
Time Frame:Every 6-8 weeks; through study completion (an average of one year)
Safety Issue:
Description:Disease control rate (DCR)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ribon Therapeutics, Inc.

Trial Keywords

  • Phase 1
  • PARP7 inhibition
  • First in Human
  • Solid Tumors
  • Interferon

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