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

Accent Therapeutics

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

sqNSCLC

Advanced Solid Tumors

High-grade Serous Ovarian Carcinoma

Squamous Non-small-cell Lung Cancer

Breast Cancer Recurrent

Triple Negative Breast Cancer

Ovarian Cancer

Treatments

Drug: ATX-295

Drug: ATX-295 and bevacizumab (or biosimilar)

Study type

Interventional

Funder types

Industry

Identifiers

NCT06799065

ATX-295-001

Details and patient eligibility

About

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.

Full 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.

Enrollment

218 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

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

Key Exclusion Criteria:

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

Other inclusion and exclusion criteria as defined in the study protocol

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

218 participants in 4 patient groups

Dose Escalation

Experimental group

Description:

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

Treatment:

Drug: ATX-295

Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC

Experimental group

Treatment:

Drug: ATX-295

Dose Expansion: Previously treated sqNSCLC

Experimental group

Treatment:

Drug: ATX-295

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

Experimental group

Treatment:

Drug: ATX-295 and bevacizumab (or biosimilar)

Trial contacts and locations

Central trial contact

Priya Rajaratnam

Data sourced from clinicaltrials.gov

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