Primary Objective:

• To determine the recommended phase II dose (RP2D) 

Secondary Objective:

• To assess the safety and tolerability, e.g. late onset toxicity (ocular toxicity)
• To evaluate the anti-tumour activity in patients with solid tumours and germline BRCA2 and/or PALB2
• To evaluate the effect on Health Related Quality of Life (HRQoL) - using Patient Reported Outcomes

Exploratory Objective:

• To evaluate the anti-tumour activity of CX-5461 in patients with ovarian cancer and pathogenic/likely pathogenic BRCA1 mutation and/or other HRD-associated somatic mutation.
• To characterize the molecular profile of tumours and evaluate predictive value of mutational signatures (including BRCA 1/ 2, PALB2, and other HRD-associated somatic mutations) in predicting response or resistance to CX-5461.
• To explore the significance of dynamic changes in ctDNA levels and plasma DNA 

Primary Objective :

• To assess whether pidnarulex induces a Rad51 response, which will be determined by an integral biomarker of percentage of cells with Rad51 nuclear foci in tumor biopsy specimens in patients with and without homologous repair deficiency (HRD) genetic mutations.

Secondary Objective :

1. To determine the safety and tolerability of pidnarulex.
2. To determine the overall response rate (complete responses plus partial responses) in patients with advanced, refractory solid tumors.
3. To measure the pharmacokinetics of pidnarulex. 
4. To evaluate other DNA damage and repair signaling markers including Top2, G4 stabilization, RPA32, pSer33-RPA32, γH2AX, 53BP1, pSer8-RPA32, pKap1m and pNBS1.

EXPLORATORY OBJECTIVE:

• To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance.

Primary Objective :

1. To define dose limiting toxicity (DLT).

2. To assess toxicity profile.

3. To determine the recommended phase 2 dose (RP2D).

4. To determine the objective response rate (ORR) (complete response [CR] and partial response [PR]).

5. To perform pharmacokinetic (PK) studies.

6. To examine the effect of CX-5461 (Pidnarulex) on gene expression profile of MYC aberrant lymphomas.

Secondary Objective :

1. To observe and record anti-tumor activity.

EXPLORATORY OBJECTIVE:

1. To determine the mechanisms of response and resistance using circulating tumor deoxyribonucleic acid (ctDNA).

2. To observe cerebral spinal fluid (CSF) distribution of CX-5461 (Pidnarulex).