RBN-2397 in Combination With Pembrolizumab in Patients With SCCL

NCT05127590 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: RBN-2397-21-002
• Study Type: interventional
• Target: 50
• Locations: 4 countries
• Sites: 19

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 and human studies to inhibit tumor growth and also shuts down the "don't kill me" signal the tumor is sending to evade the immune system. The purpose of this study is to determine if RBN-2397 in combination with pembrolizumab (a PD-1 inhibitor) has the ability to restore the response to treatment in patients with SCCL that have been previously treated with a PD-1/PD-1 ligand (PD-L1) inhibitor and have had a response followed by disease progression. The Phase 1b portion of the study will assess the safety of RBN-2397 in combination with pembrolizumab (a PD-1 inhibitor) and define the dose of RBN-2397 to be used in combination with pembrolizumab for the Phase 2. The Phase 2 portion of the study will assess the anti-tumor activity of RBN-2397 in combination with pembrolizumab.

Conditions

Advanced Squamous Non-Small Cell Lung Carcinoma

Keywords

NSCLC; Squamous Cell Lung Cancer; Squamous - NSCLC

Outcome Measures

Primary Outcomes (2)

• Determine recommended Phase 2 dose (RP2D) (Phase 1b)

  Incidence rate of Dose limiting Toxicities (DLTs) of RBN 2397 in combination with pembrolizumab

  through study completion (an average of 6 months)

• Overall Response Rate (Phase 2)

  Proportion of patients with confirmed response of CR or PR (RECIST v1.1)

  From start of treatment (C1D1) up to 78 weeks

Secondary Outcomes (5)

• Safety determined by Treatment-Emergent Adverse Events

  From start of treatment through 90 days after the last dose of study drug

• Cmax of RBN-2397

  Through Study Day 22

• Tmax of RBN-2397

  Through Study Day 22

• AUC of RBN-2397

  Through Study Day 22

• T1/2 of RBN-2397

  Through Study Day 22

Study Arms (1)

RBN-2397 in combination with pembrolizumab

EXPERIMENTAL

RBN-2397 orally in combination with the fixed approved dose of IV pembrolizumab

Drug: RBN-2397

Interventions

RBN-2397 DRUG

Continuous oral dosing with the RP2D of RBN-2397 (outpatient basis). Pembrolizumab IV infusion over 30 minutes in clinic on Day 1 of each cycle.

Also known as: Pembrolizumab, Keytruda

RBN-2397 in combination with pembrolizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of advanced/metastatic NSCLC of squamous cell histology as determined by local testing practices.
• Patients should have received prior therapy including a platinum containing chemotherapy regimen and an ICI, including anti-PD-1/anti-PD-L1, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, either sequentially or as combination of chemo + checkpoint inhibitor.
• The last regimen prior to enrolling in the study must be a checkpoint inhibitor-containing regimen where the best response for at least one tumor response assessment was stable disease (SD), partial response (PR), or complete response (CR).
• Patients experienced PD as determined by the investigator during or following their most recent treatment regimen
• Must agree to undergo tumor biopsy if medically safe and feasible. Archival biopsy samples may be submitted if fresh biopsy can't be obtained.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• CT or MRI imaging done within 28 days prior to study treatment and have at least one measurable target lesion
• 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

You may not qualify if:

• Has non-squamous histology NSCLC. Patients whose tumors have a mixed histology are ineligible.
• Patient should not have received more than two prior lines of therapy with ICI including anti-PD-1/anti-PD-L1, anti-CTLA-4 inhibitors and one prior line of a chemotherapy treatment.
• Patient is unable to swallow oral medications, has impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption (e.g., active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• Prior radiation within 2 weeks of Cycle 1 Day 1 (C1D1), except for palliative radiotherapy to a limited field. Patients must have recovered from all radiation related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non CNS disease.
• A patient with CNS metastases is excluded if:
• Has active CNS metastases (new lesions or progression from prior imaging study) requiring treatment within 28 days prior to study treatment and/or ongoing corticosteroid therapy.
• Has symptomatic or untreated leptomeningeal disease.
• Patients who discontinue prior treatment with an ICI due to irAEs.
• Has a known history of prior malignancy within the last 5 years. Except: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
• Has received a live-virus vaccination within 30 days of planned treatment start. Vaccines that do not contain live virus are permitted.
• Any of the following in the previous 6 months: myocardial infarction or current history of New York heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular anemias, or electrocardiographic evidence of acute ischemia.
• Patient has a history of prolonged QT syndrome or Torsades de pointes, and/or has a familial history of prolonged QT syndrome.
• Patient is taking a concomitant medication that is a strong inhibitor or inducer of cytochrome P450 \[CYP\]-mediated metabolism or that is metabolized by CYP 2B6, 3A4 or 2C19, 2C9, or other members of the IIC subfamily of the CYP genes and that, if underdosed, would constitute a significant risk to the patient. Individual cases may be discussed with the Medical Monitor.
• Ingestion of herbal medicines and grapefruit, grapefruit juice, pomegranate juice, star fruit, or orange marmalade (made with Seville oranges) from the start of the screening period. (Note that there are well- reported cases of CYP3A drug-drug interactions with these foodstuffs.)
• Has active autoimmune disease that has required systemic treatment in the past 12 months (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., ≤ 10 mg daily prednisolone or steroid equivalent, thyroxine, insulin, or corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, and residual hypothyroidism due to an autoimmune condition and only requiring hormone replacement, are not excluded.

Sponsors & Collaborators

• Ribon Therapeutics, Inc.: lead

Study Sites (19)

Helen F. Graham Cancer Center (Christiana Care)

Newark, Delaware, 19713, United States

Location

Cancer Treatment Centers of America

Newnan, Georgia, 30265, United States

Location

Hematology and Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Rambam Care Campus

Haifa, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Hospital Clinico Universitario De Santiago De Compostela

A Coruña, Spain

Location

NEXT Oncology Barcelona

Barcelona, Spain

Location

Vall D'Hebron Insitute of Oncology

Barcelona, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Hospital Quiron Madrid

Pozuelo de Alarcón, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

INCLIVA Biomedical Research Institute

Valencia, Spain

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Location

Imperial College London

London, United Kingdom

Location

Sarah Cannon Research Institute UK (University College London Hospitals)

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 29443986 BACKGROUND

• Gozgit JM, Vasbinder MM, Abo RP, Kunii K, Kuplast-Barr KG, Gui B, Lu AZ, Molina JR, Minissale E, Swinger KK, Wigle TJ, Blackwell DJ, Majer CR, Ren Y, Niepel M, Varsamis ZA, Nayak SP, Bamberg E, Mo JR, Church WD, Mady ASA, Song J, Utley L, Rao PE, Mitchison TJ, Kuntz KW, Richon VM, Keilhack H. PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity. Cancer Cell. 2021 Sep 13;39(9):1214-1226.e10. doi: 10.1016/j.ccell.2021.06.018. Epub 2021 Jul 22.

  PMID: 34375612 BACKGROUND

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Melissa Johnson, MD

  Tennessee Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: RBN-2397 in combination with pembrolizumab

Study Record Dates

• First Submitted: November 4, 2021
• First Posted: November 19, 2021
• Study Start: March 15, 2022
• Primary Completion: November 1, 2023
• Study Completion: December 1, 2023
• Last Updated: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3); GB (4); US (4); ES (8)