Study of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation

NCT04890613 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CX-5461-04
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 8

Brief Summary

This is an open-label, multi-center, phase 1b study designed to determine a tolerable dose of CX-5461 administered by IV infusion on Day 1 and Day 8 of a 28-day cycle in patients with selected solid tumours and associated mutations for future Phase II trials. The safety and tolerability of CX-5461, preliminary evidence of antitumor effect and the effect of CX-5461 on the Health-Related Quality of Life (HRQoL) will also be evaluated. The study will also evaluate the predictive value of mutational signatures and explore the significance of dynamic changes in ctDNA levels and plasma DNA methylome profiling in this study's exploratory cohort.

Conditions

Advanced Solid Tumor

Keywords

Pancreatic Cancer; Ovarian Cancer; Prostate Cancer; Breast Cancer; BRCA1 and/or other HRD-associated mutation; somatic or germline BRCA1/2 and/or PALB2 mutation

Outcome Measures

Primary Outcomes (1)

• Determination of Recommended Phase 2 Dose (RP2D)

  To identify the number of patients who discontinue study drug due to toxicity for each of the two dosing regimens independently.

  Safety cohort review will be conducted every 4 weeks from the date of first patient's enrollment to review safety data, until all patients have been enrolled and evaluated for toxicity.

Secondary Outcomes (3)

• Adverse Event (AE)

  After initiation of study drug, all AEs and SAEs, regardless of attribution, will be collected until 30 days following the last dose of study drug.

• Objective Response

  After initiation of study drug, through time of clinical response.

• Patient-Reported Outcomes (PRO)

  At screening, Day 1 and Day 8 of cycles 1 and 2 (each cycle is 28 days), every 8 weeks after cycle 2, and at the completion of therapy or withdrawal from study, through one month after treatment.

Other Outcomes (2)

• Characterize the molecular profile of tumors and evaluate the predictive value of mutational signatures.

  Collected at screening and at the time of disease progression.

• Correlate the significance of changes in ctDNA levels and plasma DNA methylome profiling to detect the evolution of resistant sub-clones and monitor treatment response

  Collected at screening, Day 1 and Day 8 of cycles 1 and 2 (each cycle is 28 days), every 8 weeks after cycle 2, and at the time of study discontinuation.

Study Arms (4)

Main Study Cohort patients receiving CX-5461 at 250mg/m2

EXPERIMENTAL

Eligible patients with histologically confirmed pancreatic, ovarian, prostate, or breast cancers with pathogenic/likely pathogenic germline or somatic BRCA1/2 and/or PALB2 mutation and/or genetic alterations in the specified genes will be enrolled to receive CX-5461 at a dosing concentration of 250mg/m2, delivered as a 60-minute IV infusion on Day 1 and Day 8 of a 28-day cycle.

Drug: CX-5461

Exploratory cohort patients receiving CX-5461 at 250mg/m2

EXPERIMENTAL

Eligible patients with ovarian cancer and pathogenic/likely pathogenic BRCA1 and/or other HRD-associated mutation will be enrolled to receive CX-5461 at a dosing concentration of 250 mg/m2, delivered as a 60-minute IV infusion on Day 1 and Day 8 of a 28-day cycle.

Drug: CX-5461

Main Study Cohort patients receiving CX-5461 at 325mg/m2

EXPERIMENTAL

After confirming the dose of 250mg/m2 to be safe and tolerable, eligible patients with histologically confirmed pancreatic, ovarian, prostate, or breast cancers with pathogenic/likely pathogenic germline or somatic BRCA1/2 and/or PALB2 mutation and/or genetic alterations in the specified genes will be enrolled to receive CX-5461 at a dosing concentration of 325mg/m2, delivered as a 60-minute IV infusion on Day 1 and Day 8 of a 28-day cycle.

Drug: CX-5461

Exploratory cohort patients receiving CX-5461 at 325mg/m2

EXPERIMENTAL

After confirming the dose of 250mg/m2 to be safe and tolerable, eligible patients with ovarian cancer and pathogenic/likely pathogenic BRCA1 and/or other HRD-associated mutation will be enrolled to receive CX-5461 at a dosing concentration of 325 mg/m2, delivered as a 60-minute IV infusion on Day 1 and Day 8 of a 28-day cycle.

Drug: CX-5461

Interventions

CX-5461 DRUG

150 mg sterile lyophilized powder containing 1% sucrose

Also known as: Pidnarulex

Exploratory cohort patients receiving CX-5461 at 250mg/m2; Exploratory cohort patients receiving CX-5461 at 325mg/m2; Main Study Cohort patients receiving CX-5461 at 250mg/m2; Main Study Cohort patients receiving CX-5461 at 325mg/m2

Eligibility Criteria

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

You may qualify if:

• Main study cohort:
• Histologically or cytologically confirmed malignancy of the pancreas, prostate, breast, or ovary.
• Documented evidence of pathogenic or likely pathogenic somatic or germline mutation in BRCA1/2 and/or PALB2, and/or any genetic alterations listed below as indicated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory report. The report must be submitted to and approved by study sponsor prior to registration. Other HRD-associated mutations could be eligible if prior approval by the sponsor is granted.
• ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CCNE1, CHEK1, CHEK2, CDK12, CREBBP, FANCA, FANCI, FANCL, FANC2, FANCB, FANCC, FANCD2, FANC family\*, MRE11A, MYC, NBN, NCL, PALB2, RAD50, RAD51B, RAD51C, RAD51D, RAD54L, SLFN11, PTIP, MLL3, MLL4, EZH2, CtIP(RBBP8), MUS81, CDH4, DYNLL11, TOPBP1, NBS1, CDC25A, CDC25C, RAD17, WEE1
• \* In addition to the genes already specified, the "FANC family" genes may also include the following: FANCE, FANCF, FANCG, FANCM, FANCP, FANCQ/ERCC4/XPF, FANCR/RAD51, FANCT/UBE2T, FANCU/XRCC2, FANCV/REV7/MAD2L2, and FANCW/RFWD3.
• Exploratory cohort:
• Histologically confirmed ovarian, fallopian tube or primary peritoneal cancer, with a high grade serous or high grade endometrioid histology subtype.
• Documented evidence of pathogenic or likely pathogenic germline mutation or a clinically actionable somatic mutation in BRCA1 and/or other HRD-associated mutation, as indicated in a CLIA-certified laboratory report. The report must be submitted to and approved by study sponsor prior to registration.
• Meet one of the following criteria:
• Platinum Sensitive with no evidence of disease progression within 6 months of the last dose of platinum-based chemotherapy (n=10 patients); OR
• Platinum Resistant with disease progression within 6 months of the last dose of a platinum-based chemotherapy.
• All participants:
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 within 14 days of registration.
• Radiographically documented disease progression within 28 days of registration and evaluable as per RECIST v1.1.

You may not qualify if:

• For pancreatic cancer; non-adenocarcinoma histology is excluded from this study.
• Patients with malignant bowel obstruction.
• Untreated, unstable brain or meningeal metastases or tumor. Patients with radiological evidence of stable brain metastases are eligible provided that they are asymptomatic and either do not require corticosteroids or have been treated with corticosteroids, with clinical and radiological evidence of stabilization at least 10 days after discontinuation of steroids.
• Unresolved toxicity \> CTCAE grade 1 from previous anti-cancer therapy (including radiotherapy) except hematological toxicity, Grade 1 or 2 neuropathy, and alopecia.
• Any evidence of severe or uncontrolled diseases such as but not limited to active infection, unstable or uncompensated respiratory, cardiac, neurological, hepatic, renal disease or psychiatric illness/social situations, which in the opinion of the investigator, would limit compliance with study requirements.
• Treatment with an investigational (non-registered - other than PARP inhibitor) agent within 30 days and treatment with PARP inhibitor within 14 days prior to the first dose of study medication.
• Immuno-compromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV), patients with known active hepatitis (i.e., hepatitis B or C). Note: Patients with a prior history of treated HBV infection who are antigen-negative or patients with a prior history of treated HCV infection who are HCV RNA-undetectable may be enrolled. Patients who are known to be serologically positive for human immunodeficiency virus (HIV) can enroll if their CD4+ T-cell (CD4+) counts ≥ 350 cells/uL.
• Patients who have had recent (within 14 days of registration, or until any wound has completely healed) major thoracic or abdominal surgery prior to study start, or a surgical incision that is not fully healed.
• No concurrent systemic anti-cancer therapy, biological therapy or other novel agent is to be permitted. Palliative radiotherapy may be allowed. If radiotherapy is required due to disease progression, patient will be considered off study. If radiotherapy is be used to treat non-target lesions and patients may benefit from continuing on study treatment, CX-5461 may re-commence 14 days after completion of radiotherapy. Any continuation on study treatment must be discussed with and approved by study sponsor.
• Patients may be potentially eligible where the current tissue diagnosis is confirmed histologically from biopsy of a target lesion, and the patient has had no evidence of active second malignancy which requires treatment or would confound interpretation of safety, tolerability and efficacy of CX-5461. These cases must be discussed with the medical monitor prior to confirm eligibility.
• Presence of known photosensitivity disorders (xeroderma pigmentosa, porphyria etc.). Strict adherence to protocol-defined sun-protection measures is essential for the duration of study. Patients who do not agree to follow these measures are not eligible. Patients who do not agree to use sunglasses and sun blocker (with SPF50 to UVB and a high degree of protection against UVA) if exposed to sunlight during the course of the study and for 3 months after the last dose are not eligible. Patients who plan to use sunbeds or tanning booths during the course of the study and within 3 months after the last dose are not eligible.
• Female patients who are pregnant or nursing.
• Ophthalmological active ocular surface disease at baseline (based on ophthalmological evaluation).
• History of cicatricial conjunctivitis (as evaluation by an ophthalmologist).
• Has had radiotherapy with a limited field for palliation within 1 week of the first dose of study drug, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study drug.

Sponsors & Collaborators

• Senhwa Biosciences, Inc.: lead

Study Sites (8)

University of California, Los Angeles

Santa Monica, California, 90404, United States

RECRUITING

H. Lee Moffitt Cancer Center and Research Institute Hospital

Tampa, Florida, 33612-9497, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

WITHDRAWN

Ohio State University-James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43202, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1X6, Canada

RECRUITING

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C2, Canada

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Ovarian Neoplasms; Prostatic Neoplasms; Breast Neoplasms

Interventions

CX 5461

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jason Huang, MD

  Senhwa Biosciences

  STUDY DIRECTOR

Central Study Contacts

Serena Robinson

CONTACT

1-858-552-6808; serenarobinson@senhwabio.com

Hylee Lee

CONTACT

1-858-552-6808; hylee@senhwabio.com

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: Eligible patients will be enrolled into two cohorts; Main study cohort: Patients with histologically-confirmed pancreatic, ovarian, prostate, or breast cancers with pathogenic/likely pathogenic germline or somatic BRCA1/2, PALB2, and/or other specified genetic alterations. Exploratory cohort: women with ovarian cancer and pathogenic/likely pathogenic BRCA1 and/or other HRD-associated mutation. An initial 16 eligible patients for the main cohort and 10 eligible patients for the exploratory cohort will be enrolled to receive CX-5461 at 250mg/m2, delivered as a 60-minute IV infusion on Day 1 and Day 8 of a 28-day cycle. 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 325mg/m2, delivered as a 60-minute IV infusion on Day 1 and Day 8 of a 28-day cycle.

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 18, 2021
• Study Start: September 8, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (6)