Advanced Solid TumorsPhase 1/2NCT06799065
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
A Phase 1/2 study testing ATX-295 and ATX-295 and bevacizumab (or biosimilar) in people with Advanced Solid Tumors and Breast Cancer Recurrent, run by Accent Therapeutics at 11 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Breast Cancer Recurrent, Ovarian Cancer
- What is being tested?
- ATX-295 and ATX-295 and bevacizumab (or biosimilar)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 218 participants
- Where
- 11 sitesUnited States
- Study dates
- 21 Mar 2025to 30 Aug 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
- Other inclusion and exclusion criteria as defined in the study protocol
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 11 recruiting
- Recruiting
University of Colorado Denver
Aurora, Colorado, 80045
Michael Ehrmann, 720-848-0300, MICHAEL.EHRMANN@CUANSCHUTZ.EDU
Marisa Moroney, MD
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
Davonna Felder, 313-576-9014, felderd@karmanos.org
Wasif Saif, MD
- Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
Maybelle De La Rosa, 703-783-4518, mdelarosa@nextoncology.com
Alexander Spira, MD, PhD, FACP
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Timothy Yap, MD, PhD, 713-563-1784, tyap@mdanderson.org
Timothy Yap, MD, PhD
- Recruiting
NYU Longone Health (Long Island)
Long Island City, New York, 11501
Jennifer Coffey, 212-263-4432, Jennifer.Coffey@nyulangone.org
Bhavana Pothuri, MD
- Recruiting
NYU Longone Health (Manhattan)
Manhattan, New York, 10012
Jennifer Coffey, 212-263-4432, Jennifer.Coffey@nyulangone.org
Bhavana Pothuri, MD
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
Latisha Hall, 615-329-7640
Deepak Bhamidipati, MD
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Christina Caldwell, 405-271-8001 ext. 48171, Christina-Caldwell@ouhsc.edu
Kathleen Moore, MD
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
Jordan Georg, 210-580-5921, jgeorg@nextoncology.com
Ildefonso Ismael Rodriguez Rivera, MD
- Recruiting
Florida Cancer Specialists
Sarasota, Florida, 34232
Latisha Hall, 941-377-9993
Judy Wang, MD
- Recruiting
Washington University
St Louis, Missouri, 63130
Lindsey Mayer, lindseymayer@wustl.edu
Premal Thaker, MD
About this study
Official title: A Phase 1/2, Open-Label, Dose-Escalation and Expansion First-In-Human Study of ATX-295, an Oral Inhibitor of the Kinesin Motor Protein KIF18A, as Monotherapy and in Combination With Anticancer Therapy in Patients With Locally Advanced or Metastatic Solid Tumors, Including High-Grade Serous Ovarian Cancer
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.
Read the detailed description
ATX-295 is an oral drug that inhibits a protein called KIF18A, an adenosine triphosphate (ATP)-dependent, plus end-directed mitotic kinesin. KIF18A facilitates chromosomal alignment and spindle microtubule dynamics during mitosis in certain advanced solid tumors. ATX-295 has been shown preclinically to induce robust anti-tumor activity of a variety of different solid tumors, including high-grade serious ovarian cancer, squamous non-small cell lung cancer, and triple negative breast cancer.
This is a first-in-human, Phase 1, open-label, single-arm, dose-escalation and Simon 2-Stage expansion study to evaluate the safety profile of ATX-295 and determine the recommended phase 2 dose (RP2D) as a monotherapy and in combination with bevacizumab (or a biosimilar). In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered ATX-295 as a monotherapy and in combination with bevacizumab (or a biosimilar). Exploratory objectives include examination of biomarker responses in relationship to ATX-295 exposure.
Patients with locally advanced or metastatic high-grade serious ovarian cancer and squamous non-small cell lung cancer will be enrolled to preliminarily assess the anti-tumor effect, and further examine the safety and PK of ATX-295 at the RP2D.
- Conditions
- Advanced Solid Tumors, Breast Cancer Recurrent, Ovarian Cancer, High-grade Serous Ovarian Carcinoma, Triple Negative Breast Cancer, sqNSCLC
- Being tested
- ATX-295, ATX-295 and bevacizumab (or biosimilar)
- Keywords
- KIF, KIF18A, HGSOC, Platinum-resistant, Platinum-intolerant, Platinum-refractory, sqNSCLC
- Medical subject headings
- Ovarian Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATX-295Drug
ATX-295 tablets will be taken orally
ATX-295 and bevacizumab (or biosimilar)Drug
ATX-295 tablets will be taken orally in combination with bevacizumab (or biosimilar) administered via intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Subjects will be enrolled at various doses and/or schedules of ATX-295 to identify the expansion dose(s) and RP2D Receives: Drug: ATX-295 |
| Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC | Experimental | Not described Receives: Drug: ATX-295 |
| Dose Expansion: Previously treated sqNSCLC | Experimental | Not described Receives: Drug: ATX-295 |
| Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC and select tumors | Experimental | Not described Receives: Drug: ATX-295 and bevacizumab (or biosimilar) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Adverse events graded according to CTCAE v5.0
Measured: 12 months
Secondary outcomes (5)
Preliminary evidence of antitumor activity toxicities as a monotherapy and in combination with bevacizumab (or biosimilar)
Objective response rate based on RECIST v1.1
Measured: 12 months
Measurement of phospho-histone H3 in pre- and post-treatment biopsies for a subset of participants (pharmacodynamic biomarker)
Measured: 12 months
Maximum observed plasma concentration of ATX-295 (Cmax)
Measured: 12 months
Calculated time to reach maximum observed plasma concentration (Tmax)
Measured: 12 months
Calculated area under the plasma concentration-time curve of ATX-295 (AUC0-t)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study start21 Mar 2025
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 218 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Accent Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gozde Colak, PhD, Study director, 339-707-5855
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06799065
- Sponsor's protocol ID
- ATX-295-001
- Status last verified
- Oct 2026
- First submitted
- 18 Jan 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No