Advanced/metastatic NSCLC of squamous cell histology MedDRA version: 24.0 Level: LLT Classification code 10085300 Term: Squamous non-small cell lung cancer System Organ Class: 100000004864
Conditions
Interventions
Product Code: RBN-2397
Pharmaceutical Form: Tablet
INN or Proposed INN: atamparib
Current Sponsor code: RBN-2397
Other descriptive name: (S)-5-((1-(3-oxo-3-(4-(5-(trifluoromethyl)pyrimidin-2-yl)pipera
Sponsors
Ribon Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients 18 years or older. 2. Confirmed diagnosis of advanced/metastatic NSCLC of squamous cell histology as determined by local testing practices: a. Patients should have received prior therapy including a platinum doublet 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. and b. The last regimen prior to enrolling in the study must be an approved checkpoint inhibitor-containing regimen where the best response was stable disease (SD), partial response (PR), or complete response (CR). Note: Combination of anti-PD-1/anti-PD-L1 and anti-CTLA-4 are considered one line of therapy. 3. Patients experienced PD as determined by the investigator during or following their most recent treatment regimen. Supporting information about PD must be documented. 4. Patient will have provided signed and dated informed consent prior to initiation of any study procedures. 5. Patient agrees to undergo biopsy for fresh tissue sample collection, provided the procedure to obtain the biopsy is deemed a non-significant risk procedure and is safe to do so. Patient consent for tumor biopsy collection (during Screening) is mandatory. a. Archival biopsy samples collected within 12 weeks prior to Screening are acceptable as the baseline biopsy. b. In the event that collection of a fresh biopsy is not medically feasible or in cases where the fresh biopsy is deemed not evaluable (e.g., no tumor present), submission of an archival sample collected >12 weeks prior to Screening may be requested. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 7. Have CT or MRI imaging done within 28 days prior to study treatment and have at least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 8. Patient has adequate organ function as specified by the following laboratory values: a. Patient has adequate renal function (creatinine or = 60 mL/min/1.73 m2). b. Patient has adequate hepatic function, as evidenced by a total bilirubin 3.0 × ULN and direct bilirubin > 1.5 × ULN), aspartate aminotransferase (AST), and /or alanine aminotransferase (ALT) or = 9.0 g/dL in the absence of transfusion within the previous 72 hours, platelet count > or = 100 × 10^9cells/L, and absolute neutrophil count (ANC) > or = 1.5 × 10^9 cells/L. The requirement for an ANC > or = 1.5 × 10^9/L must be independent of recent growth factor support (e.g., within the last 7 days). 9. Patient and his/her partner agree to use adequate contraception after providing written informed consent through 4 months after the last study drug dose, as follows: a. For women: Negative pregnancy test during Screening and compliant with a medically approved contraceptive regimen during and for 4 months after the treatment period or documented to be surgically sterile or postmenopausal. The use of hormonal contraception (oral or implanted) is not considered a medically approved regimen, as RBN-2397 may interfere with the efficacy of hormonal based contraception. b. For men: Compliant with a
Exclusion criteria
Exclusion criteria: 1. Has non-squamous histology NSCLC. Patients whose tumors have a mixed histology are ineligible. 2. Must not have received any other investigational systemic therapy for SCCL. 3. Should not have received more than 2 prior lines of therapy with ICI including anti-PD-1/anti-PD-L1, anti-CTLA-4 inhibitors and 1 prior line of a chemotherapy doublet treatment. 4. Unable to swallow oral medications, has impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption. 5. 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 ( or = G2 resulting from prior cancer therapies 23. Has had, within the past 6 months, the occurrence of one or more of the following events: cerebrovascular accident,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b Safety Run-in: • Determine the recommended Phase 2 dose (RP2D) of RBN-2397 in combination with pembrolizumab Phase 2: • Evaluate the antitumor activity of RBN-2397 in combination with pembrolizumab in SCCL patients with secondary resistance to prior immune checkpoint blockade inhibitor (ICI) treatment;Secondary Objective: Phase 1b Safety Run-in and Phase 2: • Assess additional measures of antitumor activity • Evaluate the safety profile and tolerability of RBN-2397 in combination with pembrolizumab • Characterize the PK of RBN-2397;Primary end point(s): Phase 1b run-in: incidence of DLTs (all available safety and PK data will be assessed by the Safety Review Committee). Phase 2: efficacy: Antitumor activity will be evaluated using RECIST v1.1 for following metrics: • ORR defined as proportion of patients with confirmed response of CR or PR. • DOR defined as the time from the earliest date of initial response date of confirmed CR or PR until the first documentation of disease progression by RECIST v1.1 or death by any cause. • PFS defined as the time from first dose of treatment to disease progression or death from any cause. • OS defined as the time from first dose of treatment to the date of death of any causes.;Timepoint(s) of evaluation of this end point: Phase 1b: Cycle 1 (21 days) Phase 2: Disease response assessments are to be performed within 28 days prior to C1D1 and repeated within 5 days before to 7 days after the first study drug dose in every other cycle starting from C3D1. After 1 year, disease response assessments will be conducted every 9 weeks. Patients will be followed for survival every 3 months after the last dose for 1 year. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety: incidence, intensity, and type of AEs, and changes in the patient’s physical examination findings, vital signs, clinical laboratory results, ECOG PS, and ECG findings. PK: plasma concentrations of RBN-2397 will be determined at all pre-dose and post-dose time points. Parameters to be calculated based on a non-compartmental model approach include, but are not limited to: • Maximum plasma concentration (Cmax) • Minimum plasma concentration (Cmin) • Time to maximum plasma concentration (Tmax) • Area under the curve (AUC) for time 0 to the last measurable value (AUC0-last) and from time 0 extrapolated to infinity (AUC0-8) (when possible, based upon the data) • AUC for time 0 to 24 hours (AUC0-24h) • T1/2;Timepoint(s) of evaluation of this end point: AEs: From C1D1 until 30 days after last dose SAEs: From ICF signature until 90 days after last dose irAEs: From C1D1 until 90 days after last dose PE: Screening and EoT Vital signs: Every visit until EoT ECOG PS: Screening, D1 of each cycle and EoT Urinalysis: screening Safety blood tests: every visit until 90-day FU visit PK: C1D1, C1D8 (phase 1b only), C1D15, C2D1 | — |
Countries
Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Manager
Ribon Therapeutics, Inc
Outcome results
None listed