Investigation of Anti-tumour Effect and Tolerability of the PARP Inhibitor 2X-121 in Patients With Metastatic Breast Cancer Selected by the 2X-121 DRP

Phase II, Open Label Clinical Study to Investigate Anti-tumour Effect and Tolerability of the PARP Inhibitor 2X-121 in Patients With Metastatic Breast Cancer Selected by the 2X-121 DRP

2X-121 is a small molecule targeted inhibitor of Poly ADP ribose polymerase (PARP), a key enzyme involved in DNA damage repair in cancer cells. The PARP inhibitor demonstrated clinical activity in a prior Phase 1 study in a number of solid tumors. 2X-121 has a novel dual-inhibitory action against both PARP 1/2 and Tankyrase 1/2. The molecule is also active in P-glycoprotein expressing cells, suggesting it may overcome some of the PARP inhibitor resistance.

The Phase 2 study is using 2x-121 DRP® biomarker in metastatic breast cancer patients to identify patients likely to respond to and benefit from treatment with 2X-121.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: PARP inhibitor 2X-121

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Herlev and Gentofte Hospital, Herlev Ringvej 75, DK-2730 Herlev
  • Vejle, Denmark, 7100
    • Vejle Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent form.
• Age 18 years or older.
• Histologically or cytological documented mBC (independent of hormone receptor, HER2 status and BRCA1 or 2 status) relapsed in 2 or more different prior therapies.
• Measurable disease by CT scan or MRI.
• With a drug response prediction (DRP) for 2X-121 with an outcome measured as being in the upper 20% likelihood of response.
• Prior chemotherapy or hormone therapy for metastatic breast cancer is allowed.
• Performance status of ECOG <= 1
• Recovered to Grade 1 or less from prior surgery or from acute toxicities of prior radiotherapy, or from treatment with cytotoxic, hormonal or biologic agents).
• >= 2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF.
• Patients with intracranial disease must be on stable or decreased level of steroid therapy (e.g. dexamethasone) for at least 7 days prior to baseline MRI. Non-enzymatic inducing ant-epileptic drugs are allowed.

• Adequate conditions as evidenced by the following clinical laboratory values:

  • Absolute neutrophils count (ANC) >= 1.5 x 10E9/L
  • Haemoglobin is at least 4.6 mmol/L
  • Platelets >= 100 x 10E9 /L
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN*
  • Serum bilirubin <= 1.5 ULN
  • Alkaline phosphatase <= 2.5 x ULN*
  • Creatinine <= 1.5 ULN
  • Blood urea within normal limits
  • Creatinine clearance within normal limits. *In case of known liver metastases with ALT and AST <= 5 x ULN and/or alkaline phosphatase <= 5 x ULN. Patients who do not conform to the transaminase and/or alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase and/or alkaline phosphatase levels are considered elevated due to other reasons than deteriorated lever capacity, may be considered for inclusion based on conferred agreement between PI and sponsor.
• Life expectancy equal or longer than 3 months.
• Sexually active females of child-producing potential must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards.

Exclusion Criteria:

• - Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period.
• Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study.
• Previous treatment with PARP inhibitors
• Any active infection requiring parenteral or oral antibiotic treatment.
• Has known HIV positivity.
• Has known active hepatitis B or C.

• Has clinical significant (i.e. active) cardiovascular disease:

  • Stroke within <= 6 months prior to day 1
  • Transient ischemic attach (TIA) within <= 6 months prior to day 1
  • Myocardial infarction within <= 6 months prior to day 1
  • Unstable angina
  • New York Hart Association (NYHA) Grade II or greater congestive heart failure (CHF)
  • Serious cardiac arrhythmia requiring medication
• Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy.
• Other medications or conditions, including surgery, that in the Investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results
• Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of 2X-121.
• Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
• Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PARP inhibitor 2X-121; 600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients	Drug: PARP inhibitor 2X-121; 600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumour efficacy after treatment with 600 mg 2X-121 as single oral agent in a 21-days cycle in mBC patients selected by the 2X-121 DRP	Overall tumor response according to RECIST	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) after administration of 2X-121 in patients with mBC	Timespan	one year
Duration of objective response after administration of 2X-121 in patients with mBC	Timespan	one year
Overall survival (OS) after administration of 2X-121 in patients with mBC	Timespan	one year
Performance status (ECOG)	To evaluate change in patient performance status by ECOG (Eastern Cooperative Oncology Group) Performance Status by a 6-step classification system	one year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse Events as assessed by CTCAE v4. to evaluate safety profile after administration of 2X-121 in patients with mBC	one year

Collaborators and Investigators

• Sponsor: Allarity Therapeutics
• Collaborators: Danish Breast Cancer Cooperative Group; Smerud Medical Research International AS

Publications and helpful links

Helpful Links

• Official Homepage of Sponsor

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2018
• Primary Completion (Actual): April 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: PARP inhibitor; Drug Response Prediction (DRP); Tankyrase 1/2 inhibitor; mRNA biomarker
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors
• Other Study ID Numbers: OV-121; SMR-3475 (Other Identifier: Smerud Medical Research International)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No