Overview

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.

Eligibility

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:
   1. Ovarian Cancer:
   2. 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.
   3. Breast Cancer:
   4. 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.
   5. Prostate Cancer:
   6. 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.