Table 1 Summary of clinical trials of CX-5461 for cancer treatment

A Phase 1, Open-Label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered CX-5461 in Patients with Advanced Haematologic Malignancies

ACTRN12613001061729 (Australia and New Zealand Clinical Trials Registry)

Open Label, Phase I trial

Completed

16 patients with advanced hematologic malignancies

CX-5461 was given as a 1-h intravenous infusion on day 1 of each 21-day cycle. Dose escalations were planned across 7 cohorts (25–450 mg/m²), initially following an accelerated design, transitioning to a 3 + 3 dose-escalation schema based on predefined toxicity criteria and DLTs of CX-5461

(1) CX-5461 administered intravenously established a maximum tolerated dose (MTD) of 170 mg/m²

(2) The dose-limiting toxicity observed was palmar-plantar erythrodysesthesia, while photosensitivity was identified as a dose-independent adverse event (AE), manageable through preventive measures

(3) CX-5461 activated p53 in tumor cells from one patient who achieved a clinical response. One patient with anaplastic large cell lymphoma experienced a prolonged partial response, and five patients with myeloma and diffuse large B-cell lymphoma attained stable disease as their best response [41]

A Phase I Study of CX5461

NCT02719977

Open Label, multi-centre Phase I trial

Completed

40 patients with incurable solid malignancies

Doses were escalated using a 3 + 3 design, which allowed 3 or 4 patients to be initially enrolled in each dose level. CX-5461 was administered as a 60-min intravenous infusion on day 1 (d1) and 8 q4w in dose levels 0–6 and d1, 8, and 15 q4w for dose levels 7–9

(1) Defective HR is investigated as a predictive biomarker for response. (2) CX-5461 is generally well tolerated, with a recommended phase II dose of 475 mg/m² on days 1, 8, and 15 every 4 weeks, and dose-limiting phototoxicity

(3) Reversion mutations in PALB2 and BRCA2 are identified upon progression following initial response in germline carriers, confirming the underlying synthetic lethal mechanism

(4) In vitro characterization of UV sensitization indicates that this toxicity is associated with the CX-5461 chemotype, independent of G4 synthetic lethality [42]

Phase Ib Expansion Study of CX-5461 in Patients With Solid Tumours and BRCA2 and/or PALB2 Mutation

NCT04890613

Open Label, multi-centre Phase 1b trial

Recruiting

52 solid tumor patients (estimated) with pathogenic/likely pathogenic germline BRCA2 and/or PALB2 mutation

(1) An initial 16 enrolled patients for the main cohort and 10 enrolled patients for the exploratory cohort will receive CX-5461 at 250 mg/m², delivered as a 60-min IV infusion on Day 1 and Day 8 of a 28-day cycle

(2) Upon completion of enrollment of all patients in the initial arms, if there are no safety concerns after review of the safety data, another two arms will open to enroll an additional 16 patients for the main cohort and 10 patients for the exploratory cohort to receive CX-5461 at 325 mg/m², delivered as a 60-min IV infusion on Day 1 and Day 8 of a 28-day cycle

No result available

Pilot Study of Pidnarulex Pharmacodynamics in Patients With Advanced Solid Tumors

NCT06606990

Open Label Phase I trial

Recruiting

40 patients (estimated) with histologically confirmed solid tumors with metastatic disease

Patients receive Pidnarulex IV over 60 min on days 1 and 8 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

No result available

Phase 1 Trial of Pidnarulex and Talazoparib in Patients With Metastatic Castration Resistant Prostate Cancer

NCT05425862

Open Label, multi-centre Phase I trial

Suspended

48 patients with adenocarcinoma of the prostate without neuroendocrine or small cell differentiation

Pidnarulex will be given as an IV infusion on days 1 and 8 of a 28-day cycle and talazoparib will be taken once daily continuously

Enrolment suspended to further assess supplementary non-clinical study data