SMARCA4/2 Inhibitor for POU2F3-Positive SCLC

NCT07551635 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-859
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

POU2F3-Positive Small Cell Lung Cancer; Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is the percentage of participants achieving complete or partial response on treatment based on RECIST v1.1 criteria (Eisenhauer et al Eur J Ca 45:228-247, 2009).

  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.

Secondary Outcomes (5)

• Median Progression-Free Survival (PFS)

  Disease assessed on treatment every 2 cycles (cycle duration=21 days) and in long-term follow-up every 8 weeks until disease progression. Disease follow-up expected up to 5 years.

• Median Overall Survival

  Survival assessed up to 5 years.

• Median Time-To-Progression (TTP)

  Disease assessed on treatment every 2 cycles (cycle duration=21 days) and in long-term follow-up every 8 weeks until disease progression. Disease follow-up expected up to 5 years.

• Median Duration of Response (DOR)

  Disease assessed on treatment every 2 cycles (cycle duration=21 days) and in long-term follow-up every 8 weeks until disease progression. Disease follow-up expected up to 5 years.

• Treatment-Related Grade 3-4 Adverse Event (AE) Rate

  Observed on treatment plus 30 days; Time frame is variable by patient as duration of treatment is event-driven per protocol section 5.5. AEs assessed on treatment days 1, 8, and 15 during cycle 1 and day 1 of every cycle thereafter (cycle duration=21 day

Study Arms (1)

FHD-286

EXPERIMENTAL

* 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.

Drug: FHD-286

Interventions

FHD-286 DRUG

SMARCA4/2 inhibitor, capsule, taken orally per protocol

FHD-286

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Foghorn Therapeutics Inc.: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jacob Sands

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacob Sands

CONTACT

617-632-6049; Jacob_Sands@dfci.harvard.edu

Jacob Sands

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: April 27, 2026
• Study Start (Estimated): September 4, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)