First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, as Monotherapy and in Combination With Anticancer Therapy in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer

NCT06799065 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ATX-295-001
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 11

Brief Summary

The goal of this study is to identify a safe and tolerated dose of the orally administered KIF18A inhibitor ATX-295. In addition, this study will evaluate the pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ATX-295 as a monotherapy and in combination with bevacizumab (or a biosimilar) in patients with locally advanced or metastatic solid tumors, including ovarian cancer and lung cancer.

Conditions

Advanced Solid Tumors; Breast Cancer Recurrent; Ovarian Cancer; Triple Negative Breast Cancer; High-grade Serous Ovarian Carcinoma; sqNSCLC; Squamous Non-small-cell Lung Cancer

Keywords

KIF; KIF18A; HGSOC; Platinum-resistant; Platinum-intolerant; Platinum-refractory; sqNSCLC

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295 as a monotherapy and in combination with bevacizumab (or biosimilar)

  Identification of a tolerable and safe dose for expansion cohorts based on dose limiting toxicities

  12 months

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Adverse events graded according to CTCAE v5.0

  12 months

Secondary Outcomes (5)

• Preliminary evidence of antitumor activity toxicities as a monotherapy and in combination with bevacizumab (or biosimilar)

  12 months

• Measurement of phospho-histone H3 in pre- and post-treatment biopsies for a subset of participants (pharmacodynamic biomarker)

  12 months

• Maximum observed plasma concentration of ATX-295 (Cmax)

  12 months

• Calculated time to reach maximum observed plasma concentration (Tmax)

  12 months

• Calculated area under the plasma concentration-time curve of ATX-295 (AUC0-t)

  12 months

Study Arms (4)

Dose Escalation

EXPERIMENTAL

Subjects will be enrolled at various doses and/or schedules of ATX-295 to identify the expansion dose(s) and RP2D

Drug: ATX-295

Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC

EXPERIMENTAL

Drug: ATX-295

Dose Expansion: Previously treated sqNSCLC

EXPERIMENTAL

Drug: ATX-295

Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC and select tumors

EXPERIMENTAL

Drug: ATX-295 and bevacizumab (or biosimilar)

Interventions

ATX-295 DRUG

ATX-295 tablets will be taken orally

Dose Escalation; Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC; Dose Expansion: Previously treated sqNSCLC

ATX-295 and bevacizumab (or biosimilar) DRUG

ATX-295 tablets will be taken orally in combination with bevacizumab (or biosimilar) administered via intravenous infusion

Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC and select tumors

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed solid tumors who have locally recurrent or metastatic disease, including HGSOC
• Refractory to or relapsed after all standard therapies with proven clinical benefit, unless as deemed by the Investigator, the subject is not a candidate for standard treatment, there is no standard treatment, or the subject refuses standard treatment after expressing an understanding of all available therapies with proven clinical benefit
• For the monotherapy expansion cohorts:
• Participants must have histological confirmation of HGSOC and be determined to be platinum-resistant, or platinum-intolerant
• Participants with sqNSCLC should have received prior treatment with a platinum, taxane, and checkpoint inhibitor
• For the combination with bevacizumab (or biosimilar): Participants must have histologically confirmed HGSOC or select solid tumors
• There is no limit to the number of prior treatment regimens
• Have measurable disease; evaluable disease is acceptable during dose escalation
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

You may not qualify if:

• Clinically unstable central nervous system (CNS) tumors or brain metastasis
• Any other concurrent anti-cancer treatment, except for hormonal blockade
• Has undergone a major surgery within 3 weeks of starting study treatment
• Medical issue that limits oral ingestion or impairment of gastrointestinal function that is expected to significantly reduce the absorption of ATX-295, however participants with a functioning distal ileostomy or colostomy may be permitted on trial
• Clinically significant (ie, active) or uncontrolled cardiovascular disease
• Need to use proton pump inhibitors on study or H2-receptor antagonists for the dose escalation portion of the study.
• Unable to transition off strong or moderate CYP3A4 inhibitors or strong inducers
• Pregnancy or intent to breastfeed or conceive a child within the projected duration of treatment

Sponsors & Collaborators

• Accent Therapeutics: lead

Study Sites (11)

University of Colorado Denver

Aurora, Colorado, 80045, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Washington University

St Louis, Missouri, 63130, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

NYU Longone Health (Long Island)

Long Island City, New York, 11501, United States

RECRUITING

NYU Longone Health (Manhattan)

Manhattan, New York, 10012, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Triple Negative Breast Neoplasms

Interventions

Bevacizumab; Biosimilar Pharmaceuticals

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Gozde Colak, PhD

  339-707-5855

  STUDY DIRECTOR

Central Study Contacts

Priya Rajaratnam

CONTACT

(339) 970-7383; clinicaltrials@accenttx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2025
• First Posted: January 29, 2025
• Study Start: March 21, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): August 30, 2027
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)