Onvansertib + Paclitaxel In TNBC

NCT05383196 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-008
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This research is being done to evaluate the safety and effectiveness of Onvansertib in combination with Paclitaxel in triple-negative breast cancer (TNBC) that has spread to other parts of the body. The names of the study interventions involved in this study are:

• Onvansertib
• Paclitaxel

Conditions

Breast Cancer; Invasive Breast Cancer; Unresectable Breast Carcinoma; Locally Advanced Breast Cancer; Metastatic Breast Cancer; Inflammatory Breast Cancer; Triple Negative Breast Cancer (TNBC); Hormone Receptor/Growth Factor Receptor-Negative Breast Cancer; HER2-negative Breast Cancer; Hormone Receptor Negative Breast Carcinoma

Keywords

Breast Cancer; Invasive Breast Cancer; Unresectable Breast Carcinoma; Locally Advanced Breast Cancer; Metastatic Breast Cancer; Inflammatory Breast Cancer; Triple Negative Breast Cancer (TNBC); Hormone Receptor/Growth Factor Receptor-Negative Breast Cancer; HER2-negative Breast Cancer; Hormone Receptor Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)-Phase Ib

  DLTs will be defined as toxicities that are considered at least possibly related to the study regimen and that fit one or more of the criteria defined per protocol

  during the first cycle of therapy (28 days).

• Incidence of Grade 3 or Higher Treatment-Related Toxicity- Phase Ib

  All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

  during the first cycle of therapy (28 days).

• Overall Response Rate (ORR) Phase II

  The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions

  Every 8 weeks until disease progression, in average 24 weeks

Secondary Outcomes (4)

• Cmax-Phase Ib

  during the first cycle of therapy (28 days)

• AUC-Phase Ib

  during the first cycle of therapy (28 days)

• Incidence of Grade 3 or Higher Treatment-Related Toxicity-Phase II

  AE assessed during treatment duration through study completion, in average 24 weeks

• Median Progression-free survival (PFS)-Phase II

  Every 8 weeks until disease progression, in average 24 weeks

Study Arms (2)

DOSE ESCALATION ONVANSERTIB + PACLITAXEL

EXPERIMENTAL

In the phase 1b, dose escalation/de-escalation will be managed using a BOIN design to identify the RP2D. The study is divided into three time periods: a screening period; a treatment period; and a post-treatment follow-up period. The names of the study interventions involved in this study are: * Onvansertib * Paclitaxel

Drug: Onvansertib; Drug: Paclitaxel

DOSE EXPANSION RP2D ONVANSERTIB + PACLITAXEL

EXPERIMENTAL

The study is divided into three time periods: a screening period; a treatment period; and a post-treatment follow-up period. The names of the study interventions involved in this study are: * Onvansertib * Paclitaxel

Drug: Onvansertib; Drug: Paclitaxel

Interventions

Onvansertib DRUG

oral administration, once daily for 21 consecutive days, followed by 7 days without drug, to complete a cycle of 28 days.

Also known as: NMS-1286937

DOSE ESCALATION ONVANSERTIB + PACLITAXEL; DOSE EXPANSION RP2D ONVANSERTIB + PACLITAXEL

Paclitaxel DRUG

once a week into your vein (by intravenous infusion) over about 30 minutes. This will continue for 3 weeks of every cycle

Also known as: Paclitaxel Injection

DOSE ESCALATION ONVANSERTIB + PACLITAXEL; DOSE EXPANSION RP2D ONVANSERTIB + PACLITAXEL

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed invasive breast cancer with unresectable locally advanced or metastatic disease, included inflammatory breast cancer
• Histologically or cytologically-confirmed triple negative breast cancer (defined as ER ≤ 10%, PR ≤ 10%, Her-2-neu negative per ASCO/CAP 2018 guidelines: 0-1+ by IHC or FISH-negative)
• Concurrent endocrine therapy will not be allowed for patients with ER/PR ≥1%
• Age ≥ 18 years
• ECOG Performance Status of 0 or 1.
• Subjects must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• Subject is not receiving any other cancer therapy. Subjects participating in surveys or observational studies are allowed.
• Subjects with treated brain metastases that are stable on imaging for at least four weeks prior to registration and who are off steroid therapy are eligible. Subjects with small, asymptomatic incidental brain metastases that require no immediate treatment, including steroids, are also eligible.
• For a male or a woman of child-bearing potential (WOCBP): Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days of the final dose of any study drug.
• Adequate contraception is defined as follows:
• Complete true abstinence.
• Consistent and correct use of one of the following methods of birth control:
• Male partner who is sterile prior to the female subjects entry into the study and is the sole sexual partner for that female patient.
• Intrauterine device (IUD) with a documented failure rate of less than 1% per year.
• WOCBP must have a negative serum or urine pregnancy test within 5 days prior to enrollment.

You may not qualify if:

• Anti-cancer chemotherapy or biologic therapy administered within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug.
• Palliative radiation therapy ≤ 2 weeks from enrollment.
• \>3 lines of chemotherapy for metastatic disease in the phase 2 portion; no limit on prior lines in the dose escalation cohort.
• Disease that has relapsed or progressed less than 6 months after most recent exposure to any taxane-based therapy in neoadjuvant, adjuvant, or metastatic setting.
• Major surgery within 6 weeks prior to treatment initiation.
• Women who are pregnant or breastfeeding.
• Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would significantly impede the absorption of an oral agent (e.g., intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
• Unable or unwilling to swallow study drug.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure (CHF) Class II or higher according to the New York Heart Association (NYHA) Functional Classification), unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
• Known active infection with COVID-19 or Human Immunodeficiency Virus (HIV), with measurable viral titer, and/or active infection with hepatitis B or C (subjects who have had a hepatitis B virus (HBV) immunization are eligible; subjects with HIV and CD4+ T-cell (CD4+) counts ≥ 350 cells/uL are eligible; subjects on established ART for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment are eligible).
• Clinically significant ascites or pleural effusions.
• Known hypersensitivity to paclitaxel.
• Grade 2 or higher peripheral neuropathy.
• Subjects with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for \> 2 years.
• Any active disease condition that would render the protocol treatment dangerous or impair the ability of the patient to receive study drug.

Sponsors & Collaborators

• Antonio Giordano, MD: lead
• Cardiff Oncology: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconness Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

onvansertib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Antonio C Giordano, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 20, 2022
• Study Start: September 30, 2022
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): February 15, 2029
• Last Updated: February 11, 2026

Record last verified: 2026-02

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: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)