Safusidenib for Brain Cancer

Recruiting at 30 trial locations

Overseen By Clinical Trials at Nuvation Bio

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nuvation Bio Inc.

Must not be taking: CYP2C8, CYP2C9, CYP3A4 substrates

Disqualifiers: Heart disease, Infections, Gastrointestinal, Psychiatric, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 16

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called safusidenib (also known as AB-218) for certain types of brain cancer. Part 1 focuses on evaluating the effectiveness of this treatment for individuals with recurring or worsening Grade 2 or 3 glioma, a type of brain tumor with a specific genetic change called an IDH1 mutation. Part 2 examines how safusidenib benefits those with a more aggressive form of this brain cancer after completing standard treatments like radiation. Suitable candidates have a specific type of brain tumor with an IDH1 mutation and have not found success with other treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. If you are taking drugs that are substrates of specific enzymes (CYP2C8, CYP2C9, CYP3A4) or transporters (P-gp, BCRP), you may need to switch to other medications or adjust your dosage. It's best to discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that safusidenib is being tested for safety in treating brain cancer, specifically in patients with a certain mutation called IDH1. Previous studies have examined how well patients handle safusidenib, and these studies indicate that the treatment is generally well-tolerated. While some people might experience side effects, they usually aren't severe enough to stop treatment.

Earlier research tested safusidenib in different doses to determine a safe and effective amount. Although detailed information on side effects isn't available, the treatment has advanced to its current trial phase due to an acceptable safety profile in earlier studies. This suggests that while some side effects might occur, they are manageable and expected for a treatment at this stage.

Participants considering joining the trial can feel reassured by this past research, knowing that safusidenib has been studied for safety in other patients with similar conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about safusidenib for brain cancer because it targets this condition in a novel way. Unlike standard treatments like surgery, radiation, and chemotherapy, safusidenib is an oral medication that acts continuously over a 28-day cycle. This drug specifically inhibits certain enzymes linked to cancer cell growth, potentially offering a new avenue for treatment with fewer invasive procedures. Its unique dosing options, ranging from 125mg to 500mg, provide flexibility to tailor the treatment to individual patient needs. This could lead to improved outcomes and better quality of life for those affected by brain cancer.

What evidence suggests that safusidenib could be an effective treatment for brain cancer?

Research shows that safusidenib may help treat IDH1-mutant gliomas, a type of brain cancer. Studies have found that safusidenib significantly lowers levels of 2-HG, a harmful substance produced by these tumors. Reducing 2-HG could help slow tumor growth. Safusidenib also penetrates the brain well, effectively targeting brain tumors. These findings suggest that safusidenib could be a promising treatment for this challenging condition. Participants in this trial will receive varying dosages of safusidenib or a placebo to further evaluate its effectiveness and safety. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with recurrent or progressive brain tumors (WHO Grade 2/3 glioma) and specific IDH1 mutations can join this trial. They must have had no more than two prior treatments, a measurable lesion, good organ function, and a life expectancy of at least three months. Women must not be able to bear children or use contraception; men should use condoms.

Inclusion Criteria

I have had 2 or fewer treatments for my cancer coming back or getting worse.

Total bilirubin: ≤ 1.5 × ULN

Absolute neutrophil count: ≥ 1,500/μL

Exclusion Criteria

Positive test results for human immunodeficiency virus (HIV) antibody.

I do not have psychiatric conditions that could affect my study participation.

I haven't had a heart attack, severe chest pain, heart failure, stroke, or similar issues in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive one of the daily oral doses of safusidenib at varying dosages to assess PK characteristics, safety, and initial efficacy

28 days per cycle, until disease progression or unacceptable toxicity

Continuous treatment with evaluations every 8 weeks

Treatment Part 2

Evaluation of the efficacy of safusidenib in Grade 2 and Grade 3 glioma cohorts

28 days per cycle, until disease progression or unacceptable toxicity

Continuous treatment with evaluations every 8 weeks

Exploratory Surgery Cohort

Participants receive oral safusidenib treatment continuously, with 28 days as a cycle, until disease progression or other criteria

28 days per cycle, until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AB-218

Trial Overview The study tests different doses of safusidenib, an oral drug for brain tumors with IDH1 mutation. Part 1 assesses safety and initial efficacy in up to 25 patients across five dosage groups. Part 2 evaluates the drug's effectiveness in larger cohorts for each tumor grade.

How Is the Trial Designed?

Group I: safusidenib 500mg qd (part 1) Experimental Treatment 1 Intervention

safusidenib 500mg qd administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.

Group II: safusidenib 500mg bid (part 1) Experimental Treatment 1 Intervention

safusidenib 500mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.

Group III: safusidenib 375mg bid (part 1) Experimental Treatment 1 Intervention

safusidenib 375mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.

Group IV: safusidenib 250mg bid (part 1) Experimental Treatment 1 Intervention

safusidenib 250mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.

Group V: safusidenib 250mg bid (Part 2) Experimental Treatment 1 Intervention

safusidenib administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment until disease progression or another reason for discontinuation occurs.

Group VI: safusidenib 125mg bid (part 1) Experimental Treatment 1 Intervention

safusidenib 125mg bid administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with safusidenib until disease progression or development of other unacceptable toxicity.

Group VII: placebo (Part 2) Placebo Group 1 Intervention

Placebo administered continuously as dosed single agent orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with placebo until disease progression or another reason for discontinuation occurs.

Who Is Running the Clinical Trial?

Nuvation Bio Inc.

Lead Sponsor

Trials

12

Recruited

1,200+

AnHeart Therapeutics Inc.

Industry Sponsor

Trials

13

Recruited

1,900+

Published Research Related to This Trial

In a phase II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

In a study of 10 patients with recurrent malignant glioma, the combination of apatinib and irinotecan resulted in a 55% objective response rate and a 78% disease control rate, indicating promising efficacy for this treatment approach.

The treatment was generally well-tolerated, with the most common side effects being gastrointestinal reactions, hypertension, and myelosuppression, suggesting that while there are some risks, the safety profile is manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. Wang, L., Liang, L., Yang, T., et al.[2022]

The combination of sorafenib and lapatinib was found to work synergistically to kill various CNS tumor cells, including those resistant to lapatinib, suggesting a promising treatment strategy for glioblastoma.

This drug combination not only enhanced the effectiveness of radiation therapy but also altered cellular mechanisms related to autophagy, indicating a complex interaction that could be leveraged for improved cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells. Hamed, HA., Tavallai, S., Grant, S., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05303519

Safusidenib Phase 2 Study in IDH1 Mutant Glioma The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 3 astrocytoma with high-risk ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11534100/

A perioperative study of Safusidenib in patients with IDH1 ... DS-1001b demonstrated good brain penetration, with reduction in 2-HG, in an optional exploratory study of tumor samples obtained from six ...

3. ecancer.org ecancer.org/en/news/26935-world-first-clinical-trial-reveals-unprecedented-insights-into-brain-cancer-treatment

World-first clinical trial reveals unprecedented insights into ... Survival rates have barely shifted in three decades, with 80 per cent of patients diagnosed with brain cancer dying within five years.

4. nature.com nature.com/articles/s41591-025-03884-4

Perioperative IDH inhibition in treatment-naive IDH-mutant ... These data suggest that mechanistically, safusidenib inhibited enzymatic features of tumor mIDH1. To transcriptionally examine pathway ...

5. biosignaling.biomedcentral.com biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02408-4

Glioma drug development benefits from emerging phase 0 ... Clinical drug development is fundamentally difficult for rare and difficult-to-treat solid tumors, for example, glioma.

6. medicine.yale.edu medicine.yale.edu/ycci/clinicaltrials/trial/safusidenib-phase-2-study-in-idh1-mutant-glioma-1/

A Phase 2, Multicenter, Clinical Study to Evaluate the Efficacy ... The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants ...

7. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-2-multicenter-clinical-study-evaluate-efficacy-and-safety-safusidenib-erbumine-patients-isocitrate-dehydrogenase-1-idh1-mutant-glioma

A Phase 2, multicenter, clinical study to evaluate the efficacy ... The purpose of this study is to see how safe and effective Safusidenib erbumine, the study drug, is in treating brain glioma and to find the recommended ...