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

NCT03562832 | Completed Phase 2 DMC

• 2 other identifiers: OV-121SMR-3475
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

PARP inhibitor; Drug Response Prediction (DRP); Tankyrase 1/2 inhibitor; mRNA biomarker

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Progression free survival (PFS) after administration of 2X-121 in patients with mBC

  one year

• Duration of objective response after administration of 2X-121 in patients with mBC

  one year

• Overall survival (OS) after administration of 2X-121 in patients with mBC

  one year

• Performance status (ECOG)

  one year

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  one year

Study Arms (1)

PARP inhibitor 2X-121

EXPERIMENTAL

600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients

Drug: PARP inhibitor 2X-121

Interventions

PARP inhibitor 2X-121 DRUG

600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients

PARP inhibitor 2X-121

Eligibility Criteria

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

You may qualify if:

• 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\*

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Allarity Therapeutics: lead
• Smerud Medical Research International AS: collaborator
• Danish Breast Cancer Cooperative Group: collaborator

Study Sites (2)

Herlev and Gentofte Hospital, Herlev Ringvej 75, DK-2730 Herlev

Herlev, 2730, Denmark

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

Related Links

• Official Homepage of Sponsor

MeSH Terms

Conditions

Breast Neoplasms

Interventions

stenoparib

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: June 20, 2018
• Study Start: June 20, 2018
• Primary Completion: April 1, 2024
• Study Completion: August 1, 2024
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)