Recruiting
Phase 2

FHD-286

Sponsor:

Dana-Farber Cancer Institute

Code:

NCT07551635

Conditions

Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

FHD-286

Study Details

Brief summary:

This is a single-arm, phase II clinical trial evaluating the efficacy and safety of FHD-286, a SMARCA4/2 inhibitor, in participants with POU2F3-expressing small cell lung cancer who have received at least one prior line of platinum-based therapy. All participants will receive FHD-286 orally once daily in 21-day cycles. The primary objective is to assess the objective response rate of FHD-286 in this population.

The names of the study drug involved in this study is:

• FHD-286 (a small-molecule SMARCA4/2 ATPase (BRG1 and BRM) inhibitor targeting the SWI/SNF chromatin remodeling complex (also known as the BAF complex)

Conditions

Small Cell Lung Cancer

Study ID

NCT07551635

Start date

Apr 28, 2026

Status verified date

Oct, 2026

Completion date

Jan 31, 2029

Anticipated

Primary completion date

Jan 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Adult age l8 years or older, who have provided written informed consent.
  • Histologically or cytologically confirmed extensive stage SCLC with documented disease progression or recurrence after prior platinum-based therapy with or without checkpoint inhibitor.
  • Positive >50% POU2F3 expression by IHC staining.
  • Participants must have measurable disease based on RECIST v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or l.
  • Participants must meet the following organ and marrow function criteria:

  • leukocytes ≥2,000/mcL
  • absolute neutrophil count (ANC) ≥1,000/mcL
  • platelets ≥50,000/mcL
  • hemoglobin ≥9 g/dL
  • total bilirubin ≤ 1.5 institutional upper limit of normal (ULN); Unless considered due to advanced malignancy involvement or Gilbert syndrome, with PI approval
  • AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN; Unless considered due to advanced malignancy involvement, with PI approval
  • ALP ≤3.0 × institutional ULN; Unless considered due to advanced malignancy involvement, with PI approval
  • prothrombin time ≤1.5 × institutional ULN or international normalized ratio (INR) ≤1.4
  • activated partial thromboplastin time (aPTT) ≤1.5 × institutional ULN; PI approval is required for a participant receiving anticoagulation therapy for treatment of a stable medical condition
  • creatinine ≤ 1.5 institutional ULN OR glomerular filtration rate (GFR) ≥40 mL/min/1.73 m2
  • left ventricular ejection fraction ≥40% by ECHO
  • no known portal vein thrombosis
  • adequate cardiovascular, respiratory, and immune system function, in the opinion of the investigator
  • Agree to abide by dietary and other considerations required during the study
  • The effects of FHD-286 on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) sexually active with male partners and fertile men sexually active with WOCBP must agree to use dual contraceptive measures (hormonal or barrier method of birth control; abstinence; condom), beginning at the screening visit and until 90 days after taking the last dose of FHD-286. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Participants must agree to refrain from donating sperm/ova from the screening visit through 90 days after the last dose of FHD-286.
  • The potential risk to fertility posed by FHD-286 is unknown. It is recommended that subjects discuss options for fertility preservation with their doctor before starting treatment.
  • See Section 5.2.2 for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents.
  • Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
  • Note: Non-child-bearing potential is defined as follows:

  • >45 years of age and has not had menses for >1 year. Participants who have been amenorrhoeic for <2 years without history of a hysterectomy or bilateral oophorectomy must have a follicle-stimulating hormone value in the postmenopausal range upon screening evaluation.
  • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Must be willing and able to swallow pills

Exclusion Criteria:

  • Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
  • Participants who are receiving any investigational therapy
  • Symptomatic brain metastases (untreated, asymptomatic brain metastases are eligible if size <6 mm).
  • Participants receiving any medications or substances that are strong inhibitors, strong inducers, or sensitive CYP3A substrates (with narrow therapeutic indices) of CYP3A enzymes are ineligible (see also Section 3.3).

  • Individuals must have stopped treatment with strong CYP3A inhibitors at least 1 week or 5 half-lives, whichever is longer, before the first dose of study drug. Strong CYP3A inhibitors may be permitted with PI approval; the FHD-286 dose should be reduced to 1.5 mg QD when a strong CYP3A inhibitor is in use.
  • Individuals must have stopped treatment with strong CYP3A inducers at least 2 weeks or 5 half-lives, whichever is longer, before the first dose of study drug. Strong CYP3A inducers may be permitted with PI approval.
  • Stable doses of immunosuppressants that are sensitive CYP3A substrates with narrow therapeutic indices may be permitted with PI approval.
  • Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
  • Taking proton pump inhibitors (PPIs). Administration of PPIs must be stopped or switched to another acid-reducing agent within 7 days before study entry. If it is medically necessary to administer PPIs concomitantly with FHD-286, this may be permitted with PI approval.
  • Taking clinically significant or increasing doses of systemic steroid therapy or any other systemic immunosuppressive medication. The use of a stable dose of such therapies may be permitted with PI approval. Local/targeted therapies, eg, inhaled or topical steroids, are acceptable. Appropriate steroid replacement to manage endocrine toxicities resulting from prior systemic anticancer therapy is acceptable.
  • Currently pregnant. Female participants must have a negative urine pregnancy test within 7 days prior to taking study treatment if of childbearing potential.
  • Currently breastfeeding.
  • Planning to become pregnant within 1 year after start of study treatment.
  • Any active cancer requiring systemic treatment or prior cancer treated within past 2 years (excluding non-melanoma skin cancer, DCIS, low risk prostate cancer not requiring treatment, superficial bladder cancer, or other low risk cancers after communication with PI).
  • Timing requirements with respect to prior therapy and surgery:

  • Radiotherapy: At least 2 weeks must have elapsed since last radiotherapy
  • Surgery: Participant must be recovered from any clinically relevant effects of any prior surgery
  • Any active infection requiring treatment (excluding HIV with undetectable viral load). Active hepatitis B (defined by presence of Hep B sAg) or C is not eligible, unless the individual has a sustained viral response to HCV treatment or immunity to prior HBV infection.
  • Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study. This includes, but is not limited to:

  • QTcF >470 msec or other factors that increase the risk of QTc prolongation. Participants with QTcF >470 msec and bundle branch block and/or pacemaker rhythm may be enrolled with approval from PI.
  • New York Heart Association class III/IV congestive heart failure of
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other prior or ongoing condition that, in the opinion of the investigator, could adversely affect the safety of the individual or impair the assessment of study results
  • GI dysfunction that would preclude adequate absorption, distribution, metabolism, or excretion of FHD-286
  • Known hypersensitivity to any component of the FHD-286 formulation
  • Prior treatment with any SMARCA2/4 inhibitor, including FHD-286

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: FHD-286

  • Baseline visit
  • Cycle 1 through End of Treatment (21-day cycles)
  • Days 1 - 21: Predetermined dose of FHD-286 1X daily. Possible dose escalation or based on tolerability.
  • 30 day follow up post-treatment discontinuation
  • Annual follow up for up to 5 years.

Interventions

FHD-286

SMARCA4/2 inhibitor, capsule, taken orally per protocol

Primary outcome measure

  • Objective Response Rate (ORR) [ Time Frame: Observed on treatment; Time frame is variable by patient as duration of treatment is event-driven per protocol section 5.5. Disease assessed on treatment every 2 cycles (cycle duration=21 days). Response follow-up expected up to 12 months. ]

Central Contacts and Locations

Central contacts

Alissa Cooper

617-632-6049alissa_cooper@dfci.harvard.edu

Alissa Cooper

alissa_cooper@dfci.harvard.edu

Locations

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Alissa Cooper

617-632-6049alissa_cooper@dfci.harvard.edu

Principal Investigator:

Alissa Cooper

More Information

Sponsor

Dana-Farber Cancer Institute

Last update posted

Oct 26, 2026

Last verified

Oct, 2026

Keywords

  • POU2F3-Positive Small Cell Lung Cancer
  • Small Cell Lung Cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-27. This information was provided to ClinicalTrials.gov by Dana-Farber Cancer Institute on 2026-10-26. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.