FHD-286 for Blood Cancers

Not currently recruiting at 5 trial locations

Overseen By Foghorn Clinical Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Foghorn Therapeutics Inc.

Must not be taking: Strong CYP3A inhibitors, Strong CYP3A inducers

Disqualifiers: Active infections, Uncontrolled illness, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment, FHD-286, for individuals with certain advanced blood cancers, focusing on safety and its action in the body. Participants may receive FHD-286 alone or with other medications like LDAC or decitabine. The trial is suitable for those with relapsed or refractory (R/R) acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or chronic myelomonocytic leukemia (CMML) who have undergone four or fewer prior treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as strong CYP3A inhibitors and inducers, and medications with narrow therapeutic indexes that are sensitive P-gp or BCRP substrates. Proton pump inhibitors should be stopped or switched 7 days before starting the trial. Some medications may be allowed with sponsor approval.

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

Research has shown that FHD-286 is promising in early trials. Prospective participants should know that patients have tolerated FHD-286 well at doses up to 7.5 mg per day, meaning most did not experience severe side effects. The drug is being tested in several ways: alone, with LDAC (a low-dose chemotherapy), and with decitabine (another chemotherapy drug). In all cases, FHD-286 has been reported as safe, with no major safety concerns so far.

These are early-stage trials, focusing on the treatment's safety and how the body processes the drug. Although the complete picture is not yet available, initial findings are encouraging. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about FHD-286 for blood cancers because it introduces a fresh approach compared to traditional treatments like chemotherapy and targeted therapies. Unlike standard therapies, FHD-286 is designed to be taken orally, which could offer a more convenient and less invasive option for patients. Additionally, FHD-286 can be combined with other medications, like LDAC and decitabine, potentially enhancing its efficacy. This flexibility and novel method of delivery make FHD-286 a promising candidate in the fight against blood cancers.

What evidence suggests that this trial's treatments could be effective for blood cancers?

Research has shown that FHD-286, one of the treatments in this trial, has potential in treating blood cancers by targeting important proteins, although it has not yet demonstrated clear improvements when used alone. In this trial, researchers are also studying FHD-286 in combination with low-dose cytarabine (LDAC), where early lab studies have shown it greatly slows cancer cell growth. Additionally, FHD-286 is being tested with decitabine, and initial research suggests that this combination might enhance the ability to fight tumors. Overall, these combinations could aid in treating advanced blood cancers by disrupting cancer cell functions. ^{1 2 3 4 6}

Who Is on the Research Team?

Sarah Reilly, MD

Principal Investigator

Foghorn Therapeutics

Are You a Good Fit for This Trial?

Adults with advanced blood cancers like myelodysplastic syndrome or acute myeloid leukemia can join this trial. They must be able to consent, follow the study plan, and have a life expectancy of at least 3 months. Key organ functions need to be stable, and they should not consume certain foods or supplements that affect specific enzymes. Women must not be pregnant or breastfeeding, and men agree to use contraception.

Inclusion Criteria

I am a woman who is either postmenopausal, cannot have children, or am not pregnant and not breastfeeding.

I have been diagnosed with an advanced blood cancer.

Subject must be able to understand and be willing to sign an informed consent

Exclusion Criteria

I am currently being treated for a severe infection.

I have a serious illness that is not under control.

Subject has any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Successive cohorts of participants receive increasing oral doses of FHD-286 as monotherapy or in combination with LDAC or decitabine to determine the RP2D(s)

8-12 weeks

Treatment

Participants receive FHD-286 orally as monotherapy or in combination with LDAC or decitabine

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FHD-286

Trial Overview The trial is testing FHD-286 alone or with other drugs (Low Dose Cytarabine/Decitabine) in patients with serious blood disorders. It's an early-phase study looking at safety, how well the body handles the drug (PK/PD), and its initial effectiveness against cancer.

How Is the Trial Designed?

Group I: FHD-286 in Combination with LDAC Experimental Treatment 2 Interventions

FHD-286 administered orally + LDAC administered subcutaneously

Group II: FHD-286 in Combination with Decitabine Experimental Treatment 2 Interventions

FHD-286 administered orally + decitabine administered intravenously (IV)

Group III: FHD-286 Monotherapy Experimental Treatment 1 Intervention

Closed to Enrollment

Who Is Running the Clinical Trial?

Foghorn Therapeutics Inc.

Lead Sponsor

Trials

3

Recruited

280+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04891757

Study Details | NCT04891757 | FHD-286 as Monotherapy ... This study is primarily intended to evaluate the safety and tolerability of FHD-286 when administered orally as monotherapy or in combination with either ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12/2327/762768/A-Phase-I-Study-of-FHD-286-a-Dual-BRG1-BRM-SMARCA4

A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4 ... Although no objective responses were observed with FHD-286 monotherapy, these findings confirm the therapeutic effect of dual inhibition of BRG1 ...

3. foghorntx.com foghorntx.com/wp-content/uploads/2023/12/122023_ASH_FHD-286-C-002_Poster_DiNardo.pdf

Preliminary Results from a Phase 1 Dose Escalation Study ... FHD-286 was evaluated in a Phase 1 dose escalation study in patients with R/R. AML or R/R MDS. • FHD-286 was tolerable and safe at continuous daily dose levels ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40238563/

A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4 ... FHD-286, a dual BRG1/BRM (Brahma related gene 1/Brahma homolog) inhibitor, were evaluated in patients with relapsed/refractory acute myeloid leukemia or ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04891757/

Clinical Trial: NCT04891757 It is primarily intended to evaluate the safety and tolerability of FHD-286 when administered orally to subjects with advanced hematologic ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4284/500356/Preliminary-Results-from-a-Phase-1-Dose-Escalation

Preliminary Results from a Phase 1 Dose Escalation Study of ... FHD-286-C-002 (NCT04891757) is a multicenter, open-label, Phase 1 dose escalation study designed to determine the safety, tolerability, dose- ...