Safusidenib for Brain Cancer

Recruiting at 8 trial locations

Overseen By Weiqing Wang

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 16

95 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new oral medication called safusidenib for patients with certain types of brain tumors that have not responded to other treatments. The drug works by targeting a specific gene mutation to slow down tumor growth. The study will evaluate the safety and effectiveness of different doses of the medication.

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.

What data supports the effectiveness of the drug AB-218 for brain cancer?

The research suggests that drugs targeting similar pathways, like BRAF and MEK inhibitors, have shown promise in treating brain tumors with specific mutations. Additionally, combinations of drugs like sorafenib and lapatinib have been effective in killing brain tumor cells, indicating potential for similar treatments. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: safusidenib 500mg qd 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 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 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 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 125mg bid 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.

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+

Findings from Research

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]

References

1. England 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. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Durable Progression-Free Survival With the Use of BRAF and MEK Inhibitors in Four Cases With BRAF V600E-Mutated Gliomas. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells. [2021]