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

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

Sponsors

Lead Sponsor: Ribon Therapeutics, Inc.

Source 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.

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.

Overall Status Recruiting
Start Date August 1, 2019
Completion Date January 31, 2021
Primary Completion Date December 31, 2020
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) through study completion (an average of one year)
Safety and tolerability through study completion (an average of one year)
Secondary Outcome
Measure Time Frame
Area under the plasma concentration Through Study Day 22
Peak plasma concentration 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 Every 6-8 weeks; through study completion (an average of one year)
Antitumor activity that may be associated with RBN-2397 treatment Every 6-8 weeks; through study completion (an average of one year)
Enrollment 120
Condition
Intervention

Intervention Type: Drug

Intervention Name: RBN-2397

Description: an oral PARP7 Inhibitor

Arm Group Label: 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Melissa L Johnson, MD Principal Investigator Tennessee Oncology, PLLC
Overall Contact

Last Name: Sudha Parasuraman, MD

Phone: 617-914-8700

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
SCRI-Denver/HealthOne | Denver, Colorado, 80218, United States Recruiting Gerald Falchook, MD 281-221-0693 [email protected] Gerald Falchook, MD Principal Investigator
SCRI-Sarasota/Florida Cancer Specialists | Sarasota, Florida, 34232, United States Recruiting Manish Patel, MD 941-377-9993 [email protected] Manish Patel, MD Principal Investigator
SCRI-Nashville/Tennessee Oncology | Nashville, Tennessee, 37203, United States Recruiting Melissa Johnson, MD 615-329-7274 [email protected] Melissa L. Johnson, MD Principal Investigator
MD Anderson Cancer Center | Houston, Texas, 77030-4009, United States Recruiting Timothy A Yap, MD, PhD 713-563-1784 [email protected] Timothy A Yap, MD, PhD Principal Investigator
Location Countries

United States

Verification Date

March 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: RBN-2397

Type: Experimental

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

Patient Data No
Study Design Info

Intervention Model: Sequential Assignment

Intervention Model Description: Dose Escalation

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov