RVU 120 (SEL120) to be tested in for treatment patients with solid tumors who have failed previous available standard therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ryvu Therapeutics S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Dec 2023 → 2 Oct 2025

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ryvu Therapeutics S.A.

External identifiers

EU CT number

2024-515131-30-00

EudraCT number

2020-005923-35

ClinicalTrials.gov

NCT05052255

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Therapy

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 objectives 2

1. 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.
2. 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.

Conditions and MedDRA coding

Relapsed / Refractory Metastatic or Advanced Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

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.
4. Performance status of Eastern Cooperative Oncology Group (ECOG) 0-2.
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 < Grade 2 toxicity sequela acceptable).
9. At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted).
10. Laboratory values at Screening and /or at Day 1 Cycle 1 pre-dose: a. Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support b. Platelets > 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 <1.5 times the upper limit of normal (ULN) f. Aspartate aminotransferase (AST ; SGOT) ≤3 x ULN; alanine aminotransferase (ALT ;SGPT) ≤3 x ULN; (≤5 x ULN for patients with advanced solid tumors with liver metastases); Alkaline phosphatase ≤ 5 x ULN for patients with advanced solid tumors with bone or liver metastases g. Creatinine clearance ≥60 mL/min (Cockcroft-Gault formula) h. Normal coagulation (elevated international normalized ratio [INR], prothrombin time or activated partial thromboplastin time [APTT] <1.3 x ULN acceptable)
11. Left ventricular ejection fraction> 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. 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 comply with the study protocol procedures and has signed the main informed consent document prior to any study specific procedure. For any optional biopsy sampling (tissue and/or blood) and long-term sample storage, additional consent is required.
17. Patients must have been off anti-cancer treatment and prohibited concomitant medications, for 4 weeks or 5 half-lives, whichever is shorter.

Exclusion criteria 13

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 celltransplant.
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 < 350 cells/μL or a history of AIDS defining opportunistic infection within the past 12 months or on established antiretroviral therapy for < 4 weeks or presenting with a viral load 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.
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 (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 clinically significant cardiovascular disease. This includes: myocardial infarction or unstable angina < 6 months prior to Screening; New York Heart Association Grade III or greater congestive heart failure; cerebrovascular accident including transient ischemic attack within the past 6 months; uncontrolled hypertension; serious or uncontrolled cardiac arrhythmia; personal history of TdP or syndrome of congenital QTc prolongation or QTc > 470 msec.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1 (Phase I), dose escalation cohorts/Part 2 Group E: • Frequency and nature of AEs, SAEs and DLTs. • Determination of the RP2D.
2. 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

Secondary endpoints 2

1. 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
2. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ryvu Therapeutics S.A.

Sponsor organisation

Ryvu Therapeutics S.A.

Address

Ul. Leona Henryka Sternbacha 2

City

Cracow

Postcode

30-394

Country

Poland

Scientific contact point

Organisation

Ryvu Therapeutics S.A.

Contact name

Rostislav Kuklik

Public contact point

Organisation

Ryvu Therapeutics S.A.

Contact name

Kamil Sitarz

Third parties 7

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications