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CIRTUVIVINT

Cirtuvivint is an investigational anti-cancer medication being studied across multiple types of cancer in clinical trials. Developed by Biosplice Therapeutics, Inc., this oral drug works by inhibiting specific enzymes called CLK1-4 and DYRK1-4, which are involved in cellular processes that can affect cancer growth. Currently being tested in phase I and II clinical trials, Cirtuvivint is being evaluated both as a standalone treatment and in combination with other cancer medications for conditions including soft tissue sarcoma, small cell lung cancer, ovarian cancer, and blood cancers like acute myeloid leukemia and myelodysplastic syndromes. This article examines the current clinical trials investigating this promising new drug.

Table of Contents

What is Cirtuvivint?

Cirtuvivint (also known as SM08502) is an investigational anti-cancer medication developed by Biosplice Therapeutics, Inc., a U.S. company. It is currently being studied in various clinical trials and has not yet been approved in Europe or by the FDA in the United States[1]. This means that it is still in the testing phase to determine its safety and effectiveness for treating different types of cancer.

Cirtuvivint is considered a “first in class” medication, which means it works in a new and unique way compared to existing cancer treatments. The drug is provided as tablets containing either 10 mg or 50 mg of the active ingredient[1].

How Cirtuvivint Works

Cirtuvivint works by inhibiting (blocking) specific enzymes in cancer cells called CDC2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs)[2]. These enzymes are involved in controlling how cells grow and divide.

Specifically, Cirtuvivint is a pan CLK and DYRK inhibitor, which means it blocks multiple forms of these enzymes. This inhibition is believed to have several anti-tumor effects, including[3]:

  • Stopping tumor growth by interfering with the cell cycle (the process by which cells divide and grow)
  • Making cancer cells more sensitive to other cancer treatments (chemosensitization)
  • Inhibiting the Wnt signaling pathway, which is often overactive in various cancers

In laboratory studies, inhibiting CLKs and DYRKs has shown promise in stopping tumor growth and making cancer cells more vulnerable to cytotoxic chemotherapy (treatments that kill cancer cells)[2].

Medical Conditions Treated with Cirtuvivint

Based on current clinical trials, Cirtuvivint is being investigated for several types of cancer[1][2][3][4]:

  • Soft Tissue Sarcoma (STS): A type of cancer that begins in the tissues that connect, support, and surround other body structures, such as muscles, fat, blood vessels, nerves, and tendons
  • Small Cell Lung Cancer (SCLC): An aggressive form of lung cancer that tends to grow and spread quickly
  • Ovarian Cancer: Specifically for patients with platinum-resistant endometrioid ovarian cancer, primary peritoneal cancer, and fallopian tube cancer with BRCA mutations or homologous recombination deficiency (HRD)
  • Acute Myeloid Leukemia (AML): A type of blood cancer that starts in the bone marrow, the soft inner part of certain bones where new blood cells are made
  • Myelodysplastic Syndromes (MDS): A group of disorders where the bone marrow doesn’t produce enough healthy blood cells

It’s important to note that Cirtuvivint is primarily being studied in patients who have advanced or recurrent cancers, or in those whose cancer has not responded well to standard treatments (known as refractory cancer)[4].

How Cirtuvivint is Administered

Cirtuvivint is an oral medication, which means it is taken by mouth as tablets. Based on current clinical trials, there are different dosing schedules being studied[1][4]:

  • 5 days on/2 days off schedule: Taking the medication for 5 consecutive days followed by 2 days without the medication
  • 2 days per week schedule: Taking the medication on 2 specific days each week (for example, on days 1, 4, 8, 11, 15, 18, 22, and 25 of a 28-day cycle)

The dosage varies in different studies, with doses ranging from 80 mg to 120 mg per day. Cirtuvivint is typically taken once daily on dosing days, at the same time each day with water[1].

Important administration guidelines include[1]:

  • Taking the medication without food (food restriction 1 hour before and 2 hours after dosing)
  • Doses delayed by 12 hours are considered missed and should not be taken
  • If vomiting occurs after taking the medication, the dose should not be retaken
  • Treatment typically continues in 28-day cycles until disease progression, unacceptable side effects, or the patient or doctor decides to stop treatment

Current Clinical Trials

Cirtuvivint is currently being studied in several clinical trials across different types of cancer[1][2][3][4]:

  1. Phase 2 trial for Soft Tissue Sarcoma: A multicenter, open-label study in Spain evaluating Cirtuvivint as a second-line treatment for advanced soft tissue sarcomas. This study aims to enroll approximately 25 patients and will assess the progression-free survival rate at 3 months[1].
  2. The SLICK Trial (Small Cell Lung Cancer Irinotecan and CDC2-like Kinase Inhibition Trial): This study is testing whether adding Cirtuvivint to irinotecan chemotherapy in patients with relapsed small cell lung cancer will be well-tolerated and improve response rate and progression-free survival[2].
  3. Phase 1 trial for Ovarian Cancer: This study is evaluating the safety and tolerability of Cirtuvivint in combination with the PARP inhibitor olaparib (Lynparza) in patients with platinum-resistant ovarian cancer who have BRCA mutations or homologous recombination deficiency (HRD)[3].
  4. Phase 1 trial for Leukemia and Myelodysplastic Syndromes: This study is testing Cirtuvivint alone and in combination with ASTX727 (a combination of decitabine and cedazuridine) for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)[4].

These clinical trials are primarily Phase 1 and Phase 2 studies, which are designed to determine the appropriate dosage, assess safety, and provide preliminary evidence of effectiveness. Phase 1 trials focus on finding the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), while Phase 2 trials further evaluate the drug’s effectiveness in treating specific cancers[2][4].

Combination Therapies with Cirtuvivint

Researchers are studying Cirtuvivint both as a standalone treatment (monotherapy) and in combination with other cancer medications. Current combination approaches include[2][3][4]:

  • Cirtuvivint + Irinotecan: For small cell lung cancer. Irinotecan is a chemotherapy drug that works by interfering with the enzymes involved in DNA replication, preventing cancer cells from dividing[2].
  • Cirtuvivint + Olaparib (Lynparza): For ovarian cancer. Olaparib is a PARP inhibitor that blocks an enzyme called poly (ADP-ribose) polymerase. This helps prevent cancer cells from repairing DNA damage, potentially making them more susceptible to death[3].
  • Cirtuvivint + ASTX727: For leukemia and myelodysplastic syndromes. ASTX727 combines two drugs: decitabine (which helps bone marrow produce normal blood cells and kills abnormal cells) and cedazuridine (which prevents the breakdown of decitabine, making it more available in the body)[4].

The rationale for these combinations is that Cirtuvivint may enhance the effectiveness of existing cancer treatments by making cancer cells more sensitive to them. This approach, known as sensitization, could potentially improve outcomes for patients with difficult-to-treat cancers[2].

Potential Side Effects

Since Cirtuvivint is still in clinical trials, the full profile of side effects is not yet completely understood. The current trials are actively monitoring for safety concerns and collecting data on adverse events[4].

In clinical trials, researchers are particularly monitoring[4]:

  • Dose-limiting toxicities (side effects severe enough to prevent increasing the dose further)
  • Treatment-emergent adverse events (problems that occur during or after treatment)
  • Treatment-related adverse events (side effects believed to be caused by the medication)
  • Serious adverse events (side effects that may require hospitalization or are life-threatening)

As part of safety monitoring, patients in Cirtuvivint trials typically undergo[4]:

  • Regular blood tests to check blood cell counts and organ function
  • Heart monitoring with echocardiography (ECHO) or multigated acquisition scan (MUGA)
  • Bone marrow aspiration and biopsies (for blood cancer studies)

If you are considering participating in a clinical trial involving Cirtuvivint, your healthcare team will discuss the potential risks and benefits in detail before you decide whether to participate. They will also monitor you closely throughout the trial for any side effects[4].

Clinical Trial Cancer Type Phase Dosing Regimen Combined With Primary Outcomes
NCT07032285 Soft Tissue Sarcoma (STS) Phase 2 80 mg/day, 5 days on/2 days off, in 28-day cycles None (monotherapy) Progression-free survival rate at 3 months
NCT07155200 Small Cell Lung Cancer Phase 1/2 Phase I: 5 days on/2 days off (starting dose) or 2 days/week Phase II: Dose determined in Phase I Irinotecan (Days 1 and 8 of 21-day cycle) Phase I: Recommended Phase II dose Phase II: Objective response rate per RECIST criteria
NCT06856499 Platinum Resistant Ovarian Cancer (BRCA/HRD positive) Phase 1 Regimen 1: 80 mg, 5 days on/2 days off Regimen 2: 120 mg, 2 days on/5 days off Olaparib (300 mg twice daily) Safety and recommended Phase 2 dose of the combination
NCT06484062 Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Phase 1 Cohort I: Daily Mon-Fri each week Cohort II: Days 1, 4, 8, 11, 15, 18, 22, 25 Cohort III: Same as Cohort II Cohort I & II: None Cohort III: ASTX727 (decitabine and cedazuridine) Maximum tolerated dose and recommended phase 2 dose

FAQ

  • What is Cirtuvivint and how does it work? Cirtuvivint (also known as SM08502) is an investigational anti-cancer drug that works by inhibiting enzymes called CDC2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These enzymes are involved in the cell cycle and other cellular processes. By blocking these enzymes, Cirtuvivint may stop cancer cells from growing and dividing. It's considered a first-in-class drug, meaning it works in a way that's different from existing cancer treatments.
  • What types of cancer is Cirtuvivint being tested for? Based on the clinical trials data, Cirtuvivint is currently being tested for several types of cancer, including: soft tissue sarcomas, small cell lung cancer, platinum-resistant ovarian cancer (including endometrioid ovarian cancer, primary peritoneal cancer, and fallopian tube cancer), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS). The trials are exploring its use both as a standalone treatment and in combination with other cancer drugs.
  • How is Cirtuvivint administered to patients? Cirtuvivint is administered orally as tablets (available in 10 mg and 50 mg strengths). The dosing schedule varies across trials, but common regimens include taking it once daily for 5 days followed by 2 days off (5/2 schedule), or twice per week (2 days on, 5 days off). The tablets are typically taken with water at the same time each day. Dietary restrictions may apply—for example, one trial specifies taking it without food (1 hour before and 2 hours after dosing).
  • What other medications is Cirtuvivint being combined with in trials? Cirtuvivint is being studied both as a standalone treatment and in combination with other cancer drugs. Current combinations being tested include: Irinotecan (a chemotherapy drug) for small cell lung cancer, Olaparib (a PARP inhibitor) for ovarian cancer, and ASTX727 (a combination of decitabine and cedazuridine) for blood cancers like acute myeloid leukemia and myelodysplastic syndromes. These combinations are being tested to see if they enhance effectiveness compared to single-drug treatments.
  • What are researchers hoping to learn from these clinical trials of Cirtuvivint? Researchers are primarily focused on several key aspects: determining the safety profile and identifying the best dose (recommended Phase 2 dose or RP2D) of Cirtuvivint alone and in combination with other drugs, evaluating how well it works against different cancers by measuring response rates and survival times, understanding how the drug moves through and affects the body (pharmacokinetics and pharmacodynamics), and identifying which dosing schedule produces the best results with manageable side effects. The trials are also looking at progression-free survival rates and overall survival in patients receiving the treatment.

Ongoing Clinical Trials on CIRTUVIVINT

  • Study of Cirtuvivint for Patients with Advanced Soft-Tissue Sarcomas as a Second-Line Treatment

    Not recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Spain

Glossary

  • CLK1-4 and DYRK1-4: Enzymes (CDC2-like kinases and dual-specificity tyrosine-regulated kinases) involved in cell cycle regulation that Cirtuvivint targets. Inhibiting these enzymes may stop cancer cells from growing.
  • Soft Tissue Sarcoma (STS): A type of cancer that begins in the tissues that connect, support and surround other body structures, such as muscle, fat, blood vessels, nerves, tendons, and the lining of joints.
  • Small Cell Lung Cancer (SCLC): An aggressive form of lung cancer that commonly starts in the bronchi (large airways in the lungs), characterized by small cancer cells that multiply quickly and form large tumors.
  • Progression-Free Survival Rate (PFSR): The percentage of patients who have not experienced worsening of their disease (progression) or death over a specific time period. In the Cirtuvivint trials, researchers are looking at PFSR at 3 months.
  • RECIST v1.1: Response Evaluation Criteria in Solid Tumors – a standardized method to measure if tumors are responding to treatment by assessing changes in tumor size and appearance on imaging scans.
  • Phase 1 Trial: The first stage of clinical testing in humans that focuses primarily on determining the safety, side effects, and appropriate dosage of a new drug.
  • Phase 2 Trial: The second stage of clinical testing that evaluates whether a drug has beneficial effects against specific diseases and continues to assess safety.
  • Recommended Phase 2 Dose (RP2D): The optimal dose of a drug determined in Phase 1 trials that balances effectiveness with manageable side effects, used for further testing in Phase 2 trials.
  • Dose-Limiting Toxicity (DLT): Side effects severe enough to prevent increasing the dose of a drug during clinical trials. DLTs help determine the maximum tolerated dose.
  • Maximum Tolerated Dose (MTD): The highest dose of a drug that can be given without causing unacceptable side effects. This helps determine appropriate dosing for patients.
  • BRCA/HRD: BRCA (Breast Cancer Susceptibility Gene) mutations and HRD (Homologous Recombination Deficiency) are genetic factors that affect how cells repair DNA damage. Tumors with these characteristics may respond differently to certain treatments.
  • Platinum Resistant Ovarian Cancer: Ovarian cancer that has stopped responding to platinum-based chemotherapy treatments (like cisplatin or carboplatin), typically defined as cancer that recurs within 6 months of completing platinum therapy.
  • Olaparib (Lynparza): A PARP inhibitor drug that blocks an enzyme involved in DNA repair, making it harder for cancer cells to fix DNA damage. It's being tested in combination with Cirtuvivint for ovarian cancer.
  • ASTX727: A combination of two drugs (decitabine and cedazuridine) used to treat certain blood cancers. Decitabine affects genetic material in cancer cells, while cedazuridine prevents the breakdown of decitabine in the body.
  • Acute Myeloid Leukemia (AML): A type of blood cancer that starts in the bone marrow and often moves quickly into the bloodstream, affecting the production of normal blood cells.
  • Myelodysplastic Syndrome (MDS): A group of disorders caused by poorly formed blood cells or ones that don't work properly, sometimes referred to as bone marrow failure disorders. MDS can sometimes progress to acute myeloid leukemia.
  • Objective Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment. It includes both complete responses (cancer disappears) and partial responses (cancer shrinks).
  • Overall Survival (OS): The length of time from either the date of diagnosis or the start of treatment that patients are still alive.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and eliminated. PK studies help determine proper drug dosing.
  • Pharmacodynamics (PD): The study of how a drug affects the body, including its mechanism of action and the relationship between drug concentration and effect.

References

  1. https://clinicaltrials.gov/study/NCT07032285
  2. https://clinicaltrials.gov/study/NCT07155200
  3. https://clinicaltrials.gov/study/NCT06856499
  4. https://clinicaltrials.gov/study/NCT06484062