Study to Determine the Maximum Tolerated Dose (MTD) of PARPi 2X-121 Monotherapy and the MTD of Dovitinib in Combination With 2X-121 in Patients With Advanced Solid Tumors

NCT05571969 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: AL-2003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase Ib, two-part, multi-center study. In Part 1, the study will evaluate the safety and tolerability, antitumor activity, pharmacokinetics, and determine the maximum tolerated dose (MTD) of 2X-121 monotherapy (at BID regimen) in patients with advanced solid tumors. In Part 2, the study will evaluate safety and tolerability, antitumor activity, pharmacokinetics and determine the MTD of dovitinib when given in combination with the MTD of 2X-121 determined in Part 1.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Determination of the MTD of 2X-121 monotherapy.

  To determine the maximum tolerated dose (MTD) of 2X-121 monotherapy given twice daily (BID) in patients with advanced solid tumors.

  Evaluated after up to approximately 2 years

• Determination of the MTD of dovitinib given in combination with 2X-121 (MTD).

  To determine the MTD of dovitinib given in combination with 2X-121 (MTD) in patients with advanced solid tumors.

  Evaluated after up to approximately 2 years

Secondary Outcomes (4)

• To evaluate the objective response rate (ORR) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2).

  Evaluated after up to approximately 2 years

• To evaluate the duration of overall response (DOR) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2).

  Evaluated after up to approximately 2 years

• To evaluate progression free survival (PFS) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2).

  Evaluated after up to approximately 2 years

• To evaluate overall survival (OS) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2).

  Evaluated after up to approximately 2 years

Study Arms (1)

2X-121 Monotherapy and Dovitinib in Combination with 2X-121 in Patients with Advanced Solid Tumors

EXPERIMENTAL

Determine the maximum tolerated dose (MTD) of 2X-121 monotherapy given twice daily (BID) and determine the MTD of dovitinib given in combination with 2X-121 (MTD) in patients with advanced solid tumors.

Drug: 2X-121 and dovitinib

Interventions

2X-121 and dovitinib DRUG

The dose levels to be evaluated in Part 1 are: Cohort 1 600 mg (morning dose: 200 mg + evening dose: 400 mg); Cohort 2 800 mg (morning dose: 400 mg + evening dose: 400 mg); Cohort 3 1000 mg (morning dose: 400 mg + evening dose: 600 mg); The dose levels to be evaluated in Part 2 are: Cohort 1 2X-121 (MTD) + 300 mg dovitinib; Cohort 2 2X-121 (MTD) + 400 mg dovitinib; Cohort 3 2X-121 (MTD) + 500 mg dovitinib;

2X-121 Monotherapy and Dovitinib in Combination with 2X-121 in Patients with Advanced Solid Tumors

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older.
• Histologically or cytological documented solid tumor.
• Available tumor biopsy (most recent) for DRP® analysis.
• Measurable disease by CT scan or MRI if possible.
• Performance status of ECOG ≤ 1.
• Recovered to Grade \<1 or baseline 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 anti-epileptic drugs are allowed.
• Adequate conditions as evidenced by the following clinical laboratory values:
• Absolute neutrophils count (ANC) ≥ 1500/mm3 (1.5 x 10³/mL)
• Hemoglobin \> 10.0 g/dL
• Platelets ≥ 100,000/mm3 (≥ 100 x 10⁹/L)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN or ≤5x ULN in presence of liver metastases
• Serum bilirubin ≤ 1.5 ULN
• Alkaline phosphatase ≤ 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.
• Any active infection requiring parenteral or oral antibiotic treatment.
• History of coagulation or bleeding disorder or subject currently on therapeutic anticoagulant medication.
• Note: Prophylactic doses of heparin or low molecular weight heparin are allowed.
• Known HIV positivity.
• Known active hepatitis B or C.
• Clinically significant (i.e. active) cardiovascular disease:
• Stroke within ≤ 6 months prior to day 1
• Transient ischemic attack (TIA) within ≤ 6 months prior to day 1
• Myocardial infarction within ≤ 6 months prior to day 1
• Unstable angina
• New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
• Serious cardiac arrhythmia requiring medication.
• Other medications or conditions, including surgery, that in the Investigator's opinion would contraindicate study participation for safety reasons or interfere with the interpretation of study results.

Sponsors & Collaborators

• Allarity Therapeutics: lead
• Amarex Clinical Research: collaborator

Study Sites (2)

Carolina BioOncology

Huntersville, North Carolina, 28078, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase Ib, two-part, multi-center study. In Part 1, the study will evaluate the safety and tolerability, antitumor activity, pharmacokinetics, and determine the maximum tolerated dose (MTD) of 2X-121 monotherapy (at BID regimen) in patients with advanced solid tumors. In Part 2, the study will evaluate the safety and tolerability, antitumor activity, and pharmacokinetics of 2X-121 (MTD) and dovitinib as combination therapy, and determine the MTD of dovitinib when given in combination with the MTD of 2X-121 determined in Part 1.

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 7, 2022
• Study Start: February 20, 2023
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2025
• Last Updated: May 7, 2025

Record last verified: 2025-05

Locations

US (2)