Relapsed / Refractory Metastatic or Advanced Solid Tumors MedDRA version: 21.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: RVU120
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: RVU120 (SEL120 previous name)
CAS Number: 1609452-30-3
Other descriptive name: 7,8-dibromo-5,6-dihydro-9-methyl-2-(1-pipera
Sponsors
Ryvu Therapeutics S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for Part 1 and Part 2: 1. Age 18 years or older 2. Histologically confirmed and/or documented advanced or metastatic tumors who have exhausted the available standard treatment(s) of the respective country and/or progressing from at least one previous systemic therapy and not eligible to further available therapy 3. At least one measurable or evaluable disease according to RECIST v1.1 (Appendix 1) 4. Performance status of Eastern Cooperative Oncology Group (ECOG) 0- 2 (Appendix 3) 5. Estimated life expectancy of at least 12 weeks 6. Toxicities incurred as a result of previous anti-cancer therapy resolved to = Grade 1 (as defined by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0, Appendix 2), except for alopecia, lymphopenia assessed as non-clinically significant, sensory neurotoxicity and erectile dysfunction that could be = Grade 2 7. At least a 4-week interval between the last received radiotherapy and the first scheduled day of dosing with RVU120 (with the exception of palliation radiotherapy which is allowed up to 2 weeks prior the first scheduled day of dosing) 8. Complete recovery from major surgery (stable and 100 x 109/L c. Only for Part 1: Hemoglobin =9 g/dL (or =2.2 mmol/L) without red blood cell transfusion within 4 weeks d. Serum albumin = 30g/L (3.0g/dL) e. Total bilirubin 50% by echocardiogram or multiple gated acquisition (MUGA) 12. Able to provide an archival or fresh tumor biopsy sample at Screening. For patients in Part 2, baseline tumor biopsy samples from progressive disease lesions, where feasible, are required 13. For women of childbearing potential (WOCBP), a negative pregnancy test must be confirmed before enrolment. WOCBP must commit to using highly effective contraception during study participation and until 6 months after the last dose of study drug (see Appendix 5). Females must also refrain from donating blood or egg (ovum) during the same timeperiod 14. For males, an effective barrier method of contraception must be used during study participation until 6 months after the last dose of study drug, if the patient is sexually active with a WOCBP. Males must also refrain from donating blood or sperm during the same time-period 15. Ability to give written, informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice 16. Capable of understanding the mandated and optional protocol requirements, is willing and able to c
Exclusion criteria
Exclusion criteria: General exclusion criteria for both Part 1 and Part 2: Any of the following will exclude a patient from enrolment: 1. Active brain metastasis (patients with treated, non-progressive brain metastases, off high-dose steroids [>20 mg prednisone or equivalent] for at least 4 weeks can be enrolled in the trial) 2. Prior history of, or planned organ or hematopoietic stem cell transplant 3. Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection and acute inflammatory conditions (including pancreatitis) 4. Known HIV infection with a CD4+ T-cell (CD4+) count of 400 copies/mL prior to enrollment or on antiretroviral therapy or prophylactic antimicrobials that are expected to cause significant drug-drug interactions or overlapping toxicities with study treatment and cannot be changed to alternative agents 5. Known positive test of / or known active diagnosis of COVID-19 viral infection 6. Ongoing significant liver disease such as cirrhosis, drug-induced liver injury, active hepatitis or chronic persistent hepatitis B and/or C •Positive serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection. Patients whose HBV infection status cannot be determined by serologic test results must be negative for HBV by PCR to be eligible for study participation (www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf) •Acute or chronic hepatitis C virus (HCV) infection. Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation 7. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RVU120 (e.g., active inflammatory bowel disease, ulcerative disease, malabsorption syndrome, short bowel syndrome, uncontrolled nausea, persistent vomiting or diarrhea) 8. Ongoing drug-induced pneumonitis 9. Concurrent participation in another investigational clinical trial 10. Taking any medications, herbal supplements or other substances (including smoking) that are known to be strong inhibitors or strong inducers or sensitive substrates of CYP1A2; with the exception of antibiotics, antifungals, and antivirals that are used as the SOC or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient and no suitable or available alternative could be found, with prior approval of the Sponsor Study Medical Director (Appendix 6) 11. Mean measurement QTcF of >470 msec on triplicate electrocardiograms (ECGs) performed within 5 minutes of each other, using QTcF (Fredericia) formula 12. Currently taking drugs that are documented in the drug package insert, to have risk of causing prolonged QTc or Torsades de Pointes (TdP) (unless these can be changed to acceptable alternatives or discontinued). Please also consult the following Credible Meds web page: https://crediblemeds.org/index.php/login/dlcheck (Appendix 7) (antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient and no suitable or available alternative could be found, can be used with prior approval by Sponsor Study Medical Director) 13. Patients with clinicall
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 (Phase I), dose escalation cohorts/Part 2 Group E • To characterize the safety and tolerability of RVU120 as single agent in patients with solid tumors Part 2 (Phase II): safety expansion and efficacy groups • To further evaluate the safety and tolerability of RVU120 as a single agent in patients with selected tumor types • To explore the anti-tumor activity of RVU120 as single agent in patients with selected tumor types;Secondary Objective: Part 1 (Phase I), dose escalation cohorts/Part 2 Group E • To determine the preliminary anti-tumor response to RVU120 • To determine the PK profile of RVU120 Part 2 (Phase II): safety expansion and efficacy groups • To determine the PK profile of RVU120, including (in a subgroup of patients) the effect of food;Primary end point(s): Part 1 (Phase I), dose escalation cohorts/Part 2 Group E • Frequency and nature of AEs, SAEs and DLTs • Determination of the RP2D Part 2 (Phase II): safety expansion and efficacy groups • Frequency and nature of AEs and SAEs The following will be assessed locally by RECIST v1.1, where applicable: • ORR • DoR • PFS • OS • CBR • CPR, when applicable;Timepoint(s) of evaluation of this end point: For Part 1 and Part 2: Throughout the study period - from Screening Visit to the Final Study Visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 (Phase I), dose escalation cohorts/Part 2 Group E The following will be assessed locally by RECIST v1.1, where applicable: • ORR • DoR • PFS • OS • CBR • CPR, when applicable PK variables including: • Cmax, Cmin, Tmax, t1/2, AUCtau Part 2 (Phase II): safety expansion and efficacy groups •Using population PK modelling and subgroup analysis, PK variables including, as possible, Cmax, Cmin, Tmax, t1/2, and AUCtau;Timepoint(s) of evaluation of this end point: For Part 1: •End of cycle 3 plus end of cycle 6 and thereafter every fourth cycle For Part 1 and Part 2: Blood samples for the assessment of the PK profile of RVU120 and its metabolites (as appropriate) in plasma will be taken at the specified timepoints provided in Appendix 13 (see Table 10 for Part 1, Table 11 for Part 2 Groups A - D, and Table 12 for Part 2 Group E). A PK blood sample will also be taken as soon as possible when there is a > Grade 1 sign/symptom of acute infection/inflammation or a . Grade 1 troponin increase. | — |
Countries
Australia, China, Czechia, France, Netherlands, Poland, Spain, United States
Contacts
Public ContactGlobal Study Leader
Ryvu Therapeutics S.A.
Outcome results
None listed