Study of PARPi 2X-121 as Monotherapy and in Combination With Dovitinib in Patients With Advanced Solid Tumors

NCT05571969 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AL-2003
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

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 (Number of Subjects With Dose-Limiting Toxicities)

  To determine the maximum tolerated dose (MTD) of 2X-121 monotherapy given twice daily (BID) in patients with advanced solid tumors. The MTD was defined as one dose level below the dose in which DLTs were observed in at least 33% of participants in a Cohort during the first 14 days of the treatment period, after addition of subjects following the first reported DLT in a Cohort (if applicable). Therefore, the table below presents number of subjects with DLTs in each Cohort during the first 14 days of treatment.

  First 14 days in each Cohort

• Determination of the MTD of Dovitinib Given in Combination With 2X-121 (MTD).

  To determine the maximum tolerated dose (MTD) of dovitinib when given in combination with the MTD of 2X-121 in patients with advanced solid tumors (Part 2 of the study). The MTD was defined as one dose level below the dose in which DLTs were observed in at least 33% of participants in a Cohort during the first 14 days of the treatment period, after addition of subjects following the first reported DLT in a Cohort (if applicable). Therefore, this outcome measure planned to evaluate the number of subjects with DLTs in each Cohort during the first 14 days of treatment.

  First 14 days of each Cohort

Secondary Outcomes (11)

• Objective Response Rate (ORR) of 2X-121 Monotherapy (Part 1) and in Combination With Dovitinib (Part 2).

  From enrollment until end of follow-up.

• Duration of Overall Response (DOR) of 2X-121 Monotherapy (Part 1) and in Combination With Dovitinib (Part 2).

  From enrollment until end of follow-up.

• Progression Free Survival (PFS) of 2X-121 Monotherapy (Part 1) and in Combination With Dovitinib (Part 2).

  From enrollment until end of follow-up.

• Overall Survival (OS) of 2X-121 Monotherapy (Part 1) and in Combination With Dovitinib (Part 2).

  From enrollment until follow-up.

• Maximum Concentration of 2X-121 (Cmax)

  Cycle 1, Day 1

Study Arms (6)

2X-121 600 mg

EXPERIMENTAL

Subjects receiving 600 mg 2X-121 BID (200 mg morning + 400 mg evening)

Drug: 2X-121 600 mg

2X-121 800 mg

EXPERIMENTAL

Subjects receiving 800 mg 2X-121 BID (400 mg morning + 400 mg evening)

Drug: 2X-121 800 mg

2X-121 1000 mg

EXPERIMENTAL

Subjects receiving 1000 mg BID (400 mg morning + 600 mg evening)

Drug: 2X-121 1000 mg

Combination 2X-121 + 300 mg dovitinib

EXPERIMENTAL

Part 2 Cohort 1 was planned to receive 2X-121 at the MTD determined in Part 1, plus 300 mg dovitinib. However, the study was terminated prior to Part 2.

Combination Product: 2X-121 + 300 mg dovitinib

Combination 2X-121 + 400 mg dovitinib

EXPERIMENTAL

Part 2 Cohort 2 was planned to receive 2X-121 at the MTD determined in Part 1, plus 400 mg dovitinib. However, the study was terminated prior to Part 2.

Combination Product: 2X-121 + 400 mg dovitinib

Combination 2X-121 + 500 mg dovitinib

EXPERIMENTAL

Part 2 Cohort 3 was planned to receive 2X-121 at the MTD determined in Part 1, plus 500 mg dovitinib. However, the study was terminated prior to Part 2.

Combination Product: 2X-121 + 500 mg dovitinib

Interventions

2X-121 600 mg DRUG

Part 1 Cohort 1 receives 600 mg 2X-121 BID (200 mg morning + 400 mg evening)

2X-121 600 mg

2X-121 800 mg DRUG

Part 1 Cohort 2 receives 800 mg 2X-121 BID (400 mg morning + 400 mg evening)

2X-121 800 mg

2X-121 1000 mg DRUG

Part 1 Cohort 3 receives 1000 mg 2X-121 BID (400 mg morning + 600 mg evening)

2X-121 1000 mg

2X-121 + 300 mg dovitinib COMBINATION_PRODUCT

Part 2 Cohort 1 planned to receive 2X-121 at the MTD determined in Part 1, plus 300 mg dovitinib.

Combination 2X-121 + 300 mg dovitinib

2X-121 + 400 mg dovitinib COMBINATION_PRODUCT

Part 2 Cohort 2 was planned to receive 2X-121 at the MTD determined in Part 1, plus 400 mg dovitinib.

Combination 2X-121 + 400 mg dovitinib

2X-121 + 500 mg dovitinib COMBINATION_PRODUCT

Part 2 Cohort 3 was planned to received 2X-121 at the MTD determined in Part 1, plus 500 mg dovitinib.

Combination 2X-121 + 500 mg dovitinib

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 (3)

Carolina BioOncology

Huntersville, North Carolina, 28078, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Interventions

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

Limitations and Caveats

Per Sponsor's decision, the study was terminated prior to the planned Part 2. Therefore, the safety, tolerability, antitumor activity, and pharmacokinetics of 2X-121 in combination with dovitinib was not determined. Sponsor also decided not to proceed with efficacy analysis from Part 1 of the study, therefore efficacy parameters like overall survival and progression-free survival were not determined.

Results Point of Contact

• Title: Jeremy Graff
• Organization: Allarity Therapeutics, Inc.

jgraff@allarity.com

001-317-452-3833

Study Officials

• Jeremy Graff

  Allarity Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• 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: March 8, 2023
• Primary Completion: February 19, 2024
• Study Completion: October 7, 2024
• Last Updated: June 1, 2026
• Results First Posted: June 1, 2026

Record last verified: 2026-05

Locations

US (3)