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Study To Assess Safety And Efficacy Of AsiDNA In Combination With Olaparib In Participants With Recurrent Solid Tumors

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ClinicalTrials.gov Identifier: NCT05700669
Recruitment Status : Recruiting
First Posted : January 26, 2023
Last Update Posted : March 31, 2023
Sponsor:
Information provided by (Responsible Party):
Onxeo

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Recurrent Epithelial Ovarian Cancer Breast Cancer Drug: AsiDNA Drug: Olaparib Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation followed by dose expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Basket Study To Assess The Safety And Efficacy Of AsiDNA™ In Combination With Olaparib In Participants With Recurrent Solid Tumors
Actual Study Start Date : February 20, 2023
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : April 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Olaparib

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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).

  8. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05700669


Contacts
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Contact: Ashish Gulati, M.D. (617) 932-7572 a.gulati@onxeo.com

Locations
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United States, Texas
Next Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Kari Cortez    210-580-9500    NXTSA_Coordinators@nextoncology.com   
Sponsors and Collaborators
Onxeo
More Information
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Responsible Party: Onxeo
ClinicalTrials.gov Identifier: NCT05700669    
Other Study ID Numbers: OX2022-203-01
First Posted: January 26, 2023    Key Record Dates
Last Update Posted: March 31, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Ovarian Epithelial
Recurrence
Disease Attributes
Pathologic Processes
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Neoplasms
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
 Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents