Study to Assess Safety and Efficacy of AsiDNA in Combination with Olaparib in Participants with Recurrent Solid Tumors

September 12, 2024 updated by: Valerio Therapeutics

A Phase 1b/2 Basket Study to Assess the Safety and Efficacy of AsiDNA™ in Combination with Olaparib in Participants with Recurrent Solid Tumors

This is a phase 1b/2 open-label, multicenter, basket study to determine the safety, anti-tumor activity, tolerability, and pharmacokinetics /pharmacodynamics of AsiDNA in combination with olaparib in participants with recurrent epithelial ovarian cancer, breast cancer and metastatic castration-resistant prostate cancer who have progressed on previous Poly (ADP-ribose) polymerase (PARP) inhibitor therapy. The study will be conducted in two phases. The Phase 1b dose escalation study designed to establish the safety, tolerability, pharmacologically active doses/ maximum tolerated dose and/or recommended phase 2 dose of AsiDNA in combination with olaparib.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase 1b/2 open-label, multicenter, basket study to determine the safety, anti-tumor activity, tolerability, and pharmacokinetics /pharmacodynamics of AsiDNA in combination with olaparib in participants with recurrent epithelial ovarian cancer, breast cancer and metastatic castration-resistant prostate cancer who have progressed on previous PARP inhibitor therapy. The study will be conducted in two phases. The Phase 1b dose escalation study designed to establish the safety, tolerability, pharmacologically active doses/ maximum tolerated dose and/or recommended phase 2 dose of AsiDNA in combination with olaparib.

Once the RP2D has been determined the Phase 2 study will proceed evaluating AsiDNA in combination with olaparib in participants with recurrent ovarian cancer, recurrent breast cancer and recurrent CRPC that failed or progressed on PARP inhibitors (PARPi) therapy. The objective of Phase 2 study is to evaluate the preliminary efficacy as measured by ORR of AsiDNA in combination with olaparib in each of the three cohorts. Eligible participants will be included to receive AsiDNA by IV infusion in addition to olaparib.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • NEXT Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female participants aged ≥18 years (no upper limit of age) at the time of consent signature.
  2. Voluntarily signed written informed consent form (ICF) before performance of any study related screening procedures.
  3. Phase 1b: Participants with advanced or metastatic ovarian, breast, or prostate cancer that have had disease progression after treatment with available therapies that are known to confer clinical benefit or are intolerant to or ineligible for standard treatment.

  4. Phase 2: Participants with:

    A. Ovarian Cancer:

    i. Female participants with histologically diagnosed relapsed high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer. ii. Participants must have ≥6 months elapsed since last platinum-based chemotherapy regimen.

    B. Breast Cancer:

    i. Histologically or cytologically confirmed recurrent breast cancer. ii. Advanced stage, metastatic disease as documented by imaging. iii. Participants must have documented status of ER, PR, and Human epidermal growth factor receptor 2 (HER2) according to ASCOCAP criteria prior to study entry. Participants must have had a biopsy to confirm hormone receptor status in the metastatic setting prior to study entry. Note: Participants with hormone receptor-positive (estrogen and/or progesterone receptor-positive) disease must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy. Endocrine therapy must have been completed at least 7 days before study treatment. iv. Participants with HER2 positive disease are not eligible for enrollment. v. Participants with ER+ tumors should have progressed on prior CDK4/6 inhibitors (in addition to hormonal therapy) to be eligible. vi. Participants with TNBC should have received sacituzumab prior to study enrollment.

    C. Prostate Cancer:

    i. Histologically or cytologically confirmed adenocarcinoma of the prostate, CRPC.

    ii. Advanced-stage, metastatic prostate cancer disease documented by soft tissue disease (per RECIST 1.1) by computerized tomography (CT)/ magnetic resonance imaging (MRI) imaging. iii. Progressive disease in the setting of medical or surgical castration (ie, CRPC) by

    PCWG3 criteria for study entry:

    • Evidence of disease progression by rising Prostate-specific antigen (PSA), or
    • Soft tissue progression per RECIST 1.1, or

    • Evidence of disease progression by observation of ≥2 new bone lesions since the initiation of last systemic therapy. iv. Surgically (bilateral orchiectomy) or medically castrated, with serum testosterone

      • 50 ng/dL (≤1.73 nmol/L) at screening. v. Medically castrated participants must be willing to continue gonadotropin- releasing hormone (GnRH) analog or antagonist for the duration of study treatment.
  5. All participants in Phase 2 must have documented progression (clinical or radiographic) on PARPi.

Exclusion Criteria:

  1. Any systemic anti-tumor-directed drug therapy within 28 days or 5 times the elimination half life (whichever is shorter) before study treatment, except for PARPi.
  2. Treatment with investigational drugs within 28 days before first study drug administration.
  3. Radical radiation therapy within four weeks prior to the first dose of study treatment or received local palliative radiation therapy for bone metastases within two weeks of the first dose of study treatment.
  4. Concomitant use of known strong cytochrome P450 (CYP) 3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is two weeks.
  5. Concomitant use of known strong (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg, bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is five weeks for enzalutamide or phenobarbital and three weeks for other agents.
  6. Other malignancy within the last 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix, and in situ breast cancer.
  7. Participant has a condition which precludes the swallowing or absorption of an oral medication.
  8. Participants with symptomatic uncontrolled brain metastases. Participants with previously treated brain metastases may participate provided they are stable and are on stable or tapering doses of steroids for at least 7 days prior to first dose of study treatment.
  9. Participant with persistent toxicities (≥ CTCAE grade 2) caused by previous cancer therapy, excluding alopecia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
Three dose levels of AsiDNA delivered intravenously weekly in combination with Olaparib
Drug: AsiDNA
All patients will receive a loading dose of AsiDNA intravenously (D1, D2, D3) followed by weekly intravenous administrations in combination with Olaparib.
Drug: Olaparib
Olaparib is given orally in combination with AsiDNA
Experimental: Dose Expansion: Recurrent Epithelial Ovarian Cancer Cohort
Recommended Phase 2 dose of AsiDNA delivered intravenously weekly in combination with Olaparib
Drug: AsiDNA
All patients will receive a loading dose of AsiDNA intravenously (D1, D2, D3) followed by weekly intravenous administrations in combination with Olaparib.
Drug: Olaparib
Olaparib is given orally in combination with AsiDNA
Experimental: Dose Expansion: Metastatic Castration-resistant Prostate Cancer Cohort
Recommended Phase 2 dose of AsiDNA delivered intravenously weekly in combination with Olaparib
Drug: AsiDNA
All patients will receive a loading dose of AsiDNA intravenously (D1, D2, D3) followed by weekly intravenous administrations in combination with Olaparib.
Drug: Olaparib
Olaparib is given orally in combination with AsiDNA
Experimental: Dose Expansion: Recurrent Breast Cancer Cohort
Recommended Phase 2 dose of AsiDNA delivered intravenously weekly in combination with Olaparib
Drug: AsiDNA
All patients will receive a loading dose of AsiDNA intravenously (D1, D2, D3) followed by weekly intravenous administrations in combination with Olaparib.
Drug: Olaparib
Olaparib is given orally in combination with AsiDNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b: Evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of AsiDNA administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Dose-limiting toxicities (DLTs) as determined by adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE 5.0)
Baseline to Week 26
Phase 1b: Evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of AsiDNA administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Dose-limiting toxicities (DLTs) as determined by physical examination
Baseline to Week 26
Phase 1b: Evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of AsiDNA administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Dose-limiting toxicities (DLTs) as determined vital signs
Baseline to Week 26
Phase 1b: Evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of AsiDNA administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Dose-limiting toxicities (DLTs) as determined by ECG
Baseline to Week 26
Phase 1b: Evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of AsiDNA administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Dose-limiting toxicities (DLTs) as determined by clinical laboratory tests
Baseline to Week 26
Phase 1b: Evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of AsiDNA administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Dose-limiting toxicities (DLTs) as determined by Eastern Cooperative Oncology Group (ECOG) performance status
Baseline to Week 26
Phase 1b: Evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of AsiDNA administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
Pharmacologically active dose (PAD) and/or Maximum Tolerated Dose (MTD).
Baseline to Week 26
Phase 2: Evaluate the anti-tumor activity of AsiDNA in combination with olaparib.
Time Frame: Baseline to Week 52
Objective Response Rate (ORR) defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on Investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria guidelines.
Baseline to Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b: Assess the pharmacokinetics (PK) of AsiDNA when administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Safety PK parameters: total exposure including Area under the plasma concentration-time curve (AUC)0-24.
Baseline to Week 26
Phase 1b: Assess the pharmacokinetics (PK) of AsiDNA when administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Safety PK parameters: total exposure including AUC0-last.
Baseline to Week 26
Phase 1b: Assess the pharmacokinetics (PK) of AsiDNA when administered in combination with olaparib in participants with advanced and/or metastatic ovarian, breast, or prostate cancer.
Time Frame: Baseline to Week 26
• Safety PK parameters: total exposure including Cmax.
Baseline to Week 26
Phase 2: Evaluate additional parameters of efficacy of AsiDNA in combination with olaparib.
Time Frame: Baseline to Week 52
• Duration of Response: time from earliest date of disease response (CR or PR) until earliest date of disease progression, or death, whichever occurs first.
Baseline to Week 52
Phase 2: Evaluate additional parameters of efficacy of AsiDNA in combination with olaparib.
Time Frame: Baseline to Week 52
• Disease Control Rate: the proportion of participants in whom a CR or PR or stable disease is observed as best overall response.
Baseline to Week 52
Phase 2: Evaluate additional parameters of efficacy of AsiDNA in combination with olaparib.
Time Frame: Baseline to Week 52
• Progression Free Survival: time from start of treatment until the first documented radiographic progressive disease or death, whichever occurs first.
Baseline to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Valerio Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2023

Primary Completion (Actual)

October 31, 2023

Study Completion (Actual)

October 31, 2023

Study Registration Dates

First Submitted

December 22, 2022

First Submitted That Met QC Criteria

January 17, 2023

First Posted (Actual)

January 26, 2023

Study Record Updates

Last Update Posted (Actual)

September 19, 2024

Last Update Submitted That Met QC Criteria

September 12, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OX2022-203-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe