A Phase 1, Open-Label Dose Escalation and Expansion Study of SNV1521 in Participants with Advanced Solid Tumors

Study Identifier:
SNV1521-101
CT.gov Identifier:
NCT06220864
EudraCT Identifier:
202552055736
EU Trial (CTIS) Number:
2025-520557-36-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

This study is testing a new medicine, SNV1521, for people with advanced cancers. The researchers want to find out if SNV1521 is safe, well-tolerated, and effective in treating solid tumors. They are investigating different doses in order to find the most effective and safe one. They are also investigating whether it can be combined with other cancer therapies.

Dose escalation evaluated once-daily (QD) doses (5-30 mg) in advanced solid tumors with germline or somatic deleterious BRCA1/2, PALB2, RAD51/52/54, CDK12, and CHEK1/2 mutations, with prior PARPi allowed.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Breast Cancers
Ovarian
Pancreas
Prostate
Other
Solid Tumor
Metastatic Cancer
Fallopian Tube
Primary Peritoneal
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: Monotherapy Dose EscalationDrug: SNV1521
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Advanced or metastatic solid tumor malignancy
  • Evaluable or Measurable disease (RECIST 1.1 Criteria).
  • ECOG Performance Status 0 or 1.
  • Life expectancy > 3 months Males or females Age 18 or older.
  • For patients with histologically or cytologically confirmed advanced or metastatic solid malignancies, the specific cohort requirements are as follows (only parts 3a, 3d, and 3d of the study conducted in China are listed here; for other cohorts, please refer to the full content of Inclusion criteria 2 in other appendices (the entire study)): Part 3a (Dose Extension – Monotherapy) - Metastatic castration-resistant prostate adenocarcinoma. - At the advanced/metastatic stage, participants have received a maximum of 2 lines of cytotoxic therapy prior to treatment. - Participants with known or suspected pathogenic germline or somatic mutations located at: BRCA1/2, PALB2, and/or RAD51B/C/D (confirmed by local laboratory testing). Part 3d (Dose Extension – Monotherapy) - HER2-negative breast cancer (TNBC or HR+). - At the advanced/metastatic stage, participants have received a maximum of 2 lines of cytotoxic therapy prior to treatment. - Participants with known pathogenic or suspected pathogenic germline or somatic mutations at BRCA1/2, PALB2, and/or RAD51B/C/D (confirmed by local laboratory testing). - Measurable disease meeting RECIST 1.1 criteria. Part 3e (Dose Extension – Monotherapy) - Non-mucinous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. - Participants must be platinum-sensitive and have achieved complete or partial remission with their most recent platinum-based chemotherapy regimen. - In advanced/metastatic stages, participants have received at most three lines of cytotoxic therapy. -- The most recent first-line chemotherapy must have included at least four cycles of platinum-based chemotherapy (bevacizumab is not permitted in this regimen). - Participants must have received one PARPi treatment. -- As a first-line maintenance therapy, participants must achieve at least 12 months of progression-free survival. -- As a second-line maintenance therapy, participants must achieve at least 6 months of progression-free survival. -- Participants who have discontinued PARP due to intolerance may be considered for enrollment, subject to approval by the medical monitor. -- Note: Participants who have never previously received PARP therapy may be considered for enrollment, subject to approval by the medical monitor.
  • Participants are willing to provide archived tumor tissue samples (formalin-fixed, paraffin-embedded (FFPE) samples collected within the past year) or are willing to undergo pre-treatment tumor biopsies. Tumor samples obtained from the most recent biopsy or resection are preferred; however, if recently collected material is unavailable, samples collected at any time during the participant's previous disease course may be accepted with sponsor approval. - Applicable only to Parts 1, 3b, 3d, and 3e: Participants willing to undergo paired tumor biopsies before and during treatment, provided their disease condition is suitable for the procedure. Note: Participants with contraindications to repeat tumor biopsies may still participate in the study, but the sponsor reserves the right to require investigators to recruit participants who can undergo biopsies during treatment to ensure a sufficient number of paired biopsy samples are collected.
  • For Parts 1, 3a, 3c, 3e, and 4, assessment may be conducted using tumor markers (PSA for prostate cancer only and CA125 for ovarian cancer) or measurable disease (RECIST 1.1/RANO-BM/PCWG3 criteria/GCIG). - Participants in Parts 2, 3b, and 3d must have measurable disease meeting RECIST 1.1 criteria. - Participants in Part 3e only: those without evidence of disease following cytoreductive surgery (if ideal cytoreductive surgery was performed before chemotherapy) and without evidence of elevated serum CA-125 levels may be considered for enrollment.
  • The physical condition score of the Eastern Oncology Collaborative Group is 0 or 1.
  • According to researchers' assessment, life expectancy is >3 months.
  • Participants must be able to tolerate oral medication and be willing to use the sponsor-provided diary to record study medication adherence daily. Note: With prior approval from the medical monitor, participants unable to swallow tablets may be permitted to use a suspension formulated with SNV1521 tablets.
  • Participants must agree to avoid pregnancy or childbirth according to the following criteria: a. Male participants must agree to take appropriate precautions to avoid pregnancy (with a contraceptive efficacy of at least 99%) from the screening period until 120 days after the last dose of the study drug (or as appropriate as required by specific countries), and must refrain from sperm donation during this period. Participants should be informed of the permissible method of preventing pregnancy with an efficacy of at least 99% (see Section 8.4.3) and confirmed to have understood. b. Women of childbearing potential must: -- have a negative serum pregnancy test result during the screening period and agree to take appropriate precautions to avoid pregnancy (with a contraceptive efficacy of at least 99%) from the screening period until 210 days after the last dose of the study drug. Participants should be informed of the permissible method of preventing pregnancy with an efficacy of at least 99% (see Section 8.4.3) and confirmed to have understood. -- Refrain from oocyte donation from 30 days before the first dose of the study drug until 210 days after the last dose. c. Women who are infertile (i.e., sterilized by hysterectomy and/or bilateral oophorectomy, or who have been amenorrhea for ≥12 months and are ≥50 years Age) are eligible for inclusion.
Exclusion criteria
  • History of other malignancy within the past 2 years
  • Prior diagnosis of Myelodysplastic syndrome or Acute Myeloid Leukemia
  • Significant cardiovascular disease within 6 months
  • Significant gastrointestinal disease
  • HIV infection with a CD4+ T-cell count < 200 cells/L and/or a detectable viral load
  • Liver dysfunction Participants with active brain metastases (except for participants in Part 3c), glioblastoma, or carcinomatous meningitis. Participants are eligible to participate in Part 1, Part 2a, Part 3a, 3b, 3d, 3e, and Parts 4a and 4b if they have undergone resection of brain metastases or radiation therapy and meet the following criteria: (1) the study treatment started at least 4 weeks after the end of brain-specific treatment (not applicable to 3c); (2) residual neurological symptoms ≤ grade 2; (3) currently receiving a stable dose of corticosteroids; and (4) a pre-study brain MRI showing no new/worsening brain lesions.
  • No history of any other malignant tumor in the past 2 years, except for the following or with prior approval from a medical monitor: - basal cell carcinoma or squamous cell carcinoma of the skin, cervical carcinoma in situ, early-stage endometrial cancer that has been thoroughly treated, superficial bladder cancer, prostate cancer with a treated Gleason score of 6 or 7, and ductal carcinoma in situ or lobular carcinoma in situ of the breast.
  • Only applicable to Part 3a: Exclusion criteria for other cancer histories - neuroendocrine disorders
  • The patient was previously diagnosed with myelodysplastic syndrome or acute myeloid leukemia.
  • Only applicable to Part 3c: Exclusion criteria for other cancer history - evidence of leptomeningeal disease.
  • Only applicable to Part 3c: Exclusion criteria for other cancer history - symptomatic or untreated spinal cord compression.
  • For Part 3c only: Exclusion criteria for Other Cancer History - For participants collecting cerebrospinal fluid (CSF) via lumbar puncture (LP): There must be no medical contraindications to lumbar puncture (including severe coagulopathy, imaging suggesting impending brain herniation or obstructive hydrocephalus, or soft tissue infection at the puncture site). Lumbar puncture may be postponed at any time if the attending physician deems the procedure unsafe due to the presence of brain metastases (e.g., size, accompanying edema, etc.).
  • This applies only to Part 3e: Exclusion criteria for other cancer histories - non-epithelial tumors (i.e., sarcomas and neuroendocrine tumors).
  • Only applicable to Part 3e: Exclusion criteria for other cancer histories - Ovarian carcinosarcoma
  • This applies only to Part 4: Exclusion criteria for Other Cancer Histories - Participants with histopathological features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet ring cell cancers are not eligible for enrollment.
  • Exclusion criteria for Part 4: Other cancer history - Received blood products or growth factor support therapy within the past 14 days.
  • Exclusion criteria only for Part 4: Other cancer history - Participants whose bone and soft tissue progression is not evaluable.
  • The specific Exclusion criteria for the prior PARP inhibitor cohort are as follows: - Parts 1, 2, and 3e: Prior treatment with more than one PARP inhibitor and subsequent disease progression. - Parts 3a, 3b, 3c, 3d, 4a, and 4b: Prior treatment with a PARP inhibitor. Note: Patients who discontinue prior PARP inhibitor treatment due to intolerance and have no evidence of disease progression are eligible to participate in the study. These patients must be reviewed and approved by a medical monitor before the screening process begins.
  • This applies only to Part 1a refill, Part 1b, Part 3b, Part 3c, and Part 3d: Patients who experienced disease progression (platinum resistance) during or within 6 months of completing platinum-based chemotherapy. Example: Patients who received FOLFIRINOX but did not receive oxaliplatin due to intolerance and experienced disease progression after discontinuation of oxaliplatin are eligible for the study. Note: Part 1a refill and Part 1b participants who experienced disease progression after prior platinum-based chemotherapy may be eligible for the study with the approval of the medical monitor. Note: Platinum sensitivity is determined by the time interval between the last platinum-based drug administration and the recorded date of disease progression (progression ≤ 6 months = platinum resistance).
  • Only applicable to Part 2: those who have previously received HER3-targeted therapy.
  • Only applicable to Part 2: those who have previously received ADC therapy targeting TOP1.
  • Part 4 applies only: a. Only for mCRPC participants: those who have previously received any novelty hormonal therapy (NHA), poly(adenosine Phosphate ribose) polymerase inhibitor (PARPi), lutetium prostate-specific membrane antigen (Lu-PSMA) therapy, or platinum-based chemotherapy. b. Only for mCSPC participants: those who have previously received any PARPi, platinum-based therapy, NHA, immuno-oncology (IO) therapy, or radiopharmaceutical therapy.
  • Unrelieved toxicities (CTCAE grade >1) from previous anticancer treatments, excluding hair loss. Participants with ≤2 grade toxicities from previous antitumor treatments that are considered irreversible are allowed, provided that the toxicity is not listed in the Exclusion criteria and the investigator and medical monitor unanimously agree to continue the trial.
  • He also participated in another interventional clinical study.
  • For Parts 1, 2, 3a, 3b, 3d, 3e, 4a, and 4b, participants must have received therapeutic or palliative radiation therapy within 2 weeks prior to Day 1 of the study. Any participants with radiation-related toxicities must recover to grade ≤1. - Only for Part 3c: Prior stereotactic or highly conformal radiation therapy within 1 week prior to the first dose in this study, or whole-brain radiation therapy within 2 weeks prior.
  • 20
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  • twenty one Prior to the first dose of the investigational drug, the patient must have received treatment with an anticancer drug or investigational drug within the following time intervals: - For chemotherapy or targeted small molecule therapy, at least 14 days. - For prior monoclonal antibodies, at least 28 days. - For all other investigational drugs or devices, at least 28 days or 5 half-lives (whichever is shorter). Note: Concomitant hormone therapy is permitted for prostate or breast cancer.
  • 21
  • :
  • twenty two Patients must have had severe cardiovascular disease within the 6 months prior to starting treatment, including myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA Class II), unstable angina, arrhythmias requiring medical treatment; a personal or first-degree family history of congenital long QT syndrome, a family history of unexplained sudden death before age 40, a personal history of torsades de pointes, and use of any medication known to prolong the QT interval. Note: All oral doses of ondansetron are permitted, with an intravenous dose up to 16 mg.
  • 22
  • :
  • twenty three Severe gastrointestinal diseases that lead to difficulty in oral intake, malabsorption, or the need for parenteral nutrition; uncontrolled inflammatory bowel disease.
  • 23
  • :
  • twenty four Active infection requiring intravenous antibiotics within one week prior to the start of treatment.
  • Known HIV infection, with a CD4+ T cell count < 200 cells/μL, and/or detectable viral load according to the testing parameters, and/or currently receiving ART regimens containing potent CYP3A4/5 inhibitors or inducers, and/or having received a new ART regimen within 28 days prior to the start of study treatment.
  • Known history of drug-induced liver injury; alcoholic liver disease; non-alcoholic steatohepatitis; primary biliary cirrhosis; or persistent extrahepatic obstruction caused by gallstones, cirrhosis, or portal hypertension.
  • Participants who have undergone major surgery within 4 weeks prior to the start of the study or who have postoperative complications that prevent them from adhering to the protocol assessment and procedures.
  • Participants unable to swallow tablets. Note: With prior approval from the medical monitor, participants unable to swallow tablets may be permitted to use a suspension of SNV1521 tablets.
  • Known allergy to any medication used during administration.
  • Any disease or condition that, in the researchers' opinion, may affect a participant's ability to provide written informed consent and/or comply with all prescribed research procedures.
  • A history of (non-infectious) interstitial lung disease (ILD)/non-infectious pneumonia requiring steroid treatment, current ILD/non-infectious pneumonia, or imaging studies at screening that cannot rule out suspected ILD/non-infectious pneumonia.
  • Applicable only to Part 4a: Active infection or other medical conditions contraindicated for the use of systemic steroids (prednisone/ prednisone). (ii) Low serum potassium (<3.5 mmol/L). (iii) History of uncontrolled pituitary or adrenal dysfunction.
  • Breastfeeding female participants.
  • Potent CYP3A4/5 inhibitors or inducers cannot be discontinued within the following timeframes prior to the start of study treatment: - For inhibitors, discontinuation must be made at least 5 half-lives or 14 days (whichever is longer) before the first administration of the study drug. - For inducers, discontinuation must be made at least 28 days before the first administration of the study drug.
  • Acid-suppressing agents, such as proton pump inhibitors (PPIs) (e.g., omeprazole, esomeprazole, pantoprazole, lansoprazole, and rabeprazole), cannot be discontinued before the start of study treatment. H2 receptor antagonists (e.g., ranitidine, famotidine, nizatidine, and cimetidine) are permitted.
  • Parts 1, 2, 3a, 3b, 3d, or 3e: Participants with a history of treated brain metastases may use antiepileptic drugs. - Part 3c: Use of antiepileptic drugs is permitted, provided they are not potent CYP3A4/5 inhibitors or inducers.
  • For Part 4b only: Combined use of potent P-glycoprotein inducers.
  • Only applicable to Part 4b: Combined use of BCRP substrates.
  • Only applicable to Part 4b: Combined use of OATP1B1 and OATP1B3 substrates.
  • Participants whose laboratory test values meet the definitions in the table below at the time of screening: - Platelets (Parts 1 and 3): ≤100 × 10^9/L; Platelets (Part 2): ≤150 x 10^9/L - Hemoglobin (Parts 1 and 3): ≤9 g/dL or <5.6 mmol/L (this criterion cannot be met by transfusion within 2 weeks prior to the screening laboratory test); Hemoglobin (Part 2): ≤11 g/dL or <6.8 mmol/L (this criterion cannot be met by transfusion within 2 weeks prior to the screening laboratory test) ANC (Parts 1 and 3): ≤1.5 × 10^9/L; ANC (Part 2): ≤2.5 × 10^9/L ALT: >2.5 × in-hospital ULN AST: >2.5 × in-hospital ULN Total bilirubin: >1.5 × In-hospital ULN, unless conjugated bilirubin ≤ ULN (conjugated bilirubin testing is only required if total bilirubin exceeds ULN). If there is no in-hospital ULN, direct bilirubin must be < 40% of total bilirubin. Calculated CrCl*: CrCl < 50 mL/min INR: Participants not receiving anticoagulation therapy > 1.5 × in-hospital ULN PT: Participants not receiving anticoagulation therapy > 1.5 × in-hospital ULN aPTT: Participants not receiving anticoagulation therapy > 1.5 × in-hospital ULN *Cockcroft-Gault (1976): CrCl = ([140 - Age] × weight [kg]) / (72 × serum creatinine) × 0.85 (female) or according to institutional guidelines. CrCl above 50 mL/min is permissible by 24-hour urine collection.
  • Abnormalities in the rhythm, conduction, or morphology of a resting electrocardiogram that are of clinical significance.
  • A baseline QT interval (QTcF) corrected for heart rate using the Fridricia formula is ≥ 470 msec, based on the average of three measurements. Resting ECGs at two or more time points within a 24-hour period show a QTcF ≥ 470 msec.
  • Female participants of childbearing age who had a positive urine or serum pregnancy test within 7 days prior to the start of the study, or whose positive bHCG test, as confirmed by obstetrics and gynecology, does not necessarily indicate a continuing pregnancy.
  • Active or chronic HBV infection (participants with a history of infection but who have recovered are not excluded).
  • Active HCV infection. Participants who have completed effective antiviral treatment and whose infection has been confirmed to be eradicated after treatment are eligible to participate in the study.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Justin Call
Status
Recruiting
Condition(s) Treated at Site
Breast Cancers
Ovarian
Pancreas
Prostate
Other
Solid Tumor
Metastatic Cancer
Fallopian Tube
Primary Peritoneal
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Emiliano Calvo
Status
Recruiting
Condition(s) Treated at Site
Breast Cancers
Ovarian
Pancreas
Prostate
Other
Solid Tumor
Metastatic Cancer
Fallopian Tube
Primary Peritoneal