DAN-222 + Niraparib for Breast Cancer

No longer recruiting at 8 trial locations

Overseen By Kristen Foye

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Dantari, Inc.

Must not be taking: Antiepileptics, CYP3A4 inhibitors

Disqualifiers: Pregnancy, QT prolongation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, DAN-222, for individuals with metastatic breast cancer that hasn't responded well to at least two prior treatments. The study will first test DAN-222 alone and then in combination with another drug, niraparib (also known as Zejula), to assess their safety and tolerability. It targets those with HER2-negative breast cancer, meaning their cancer lacks a protein that typically accelerates growth. Participants should have experienced cancer progression despite previous treatments and have measurable disease. As a Phase 1 trial, this research aims to understand how DAN-222 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like enzyme-inducing antiepileptic drugs or those that affect the QT interval. You may need to stop or switch these medications before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that DAN-222 was safe and well-tolerated in patients with advanced HER2-negative breast cancer. Patients managed the treatment well, even those who had received many prior treatments. The combination with niraparib (an approved cancer drug) was also evaluated for safety. Niraparib, already approved for other cancer types, is generally considered safe.

These findings suggest that, so far, the treatments have not caused unexpected or severe side effects in the groups studied. However, as this is an early-stage study, further research is needed to confirm these results in larger groups. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DAN-222 for metastatic breast cancer because it represents a new approach to treatment. Unlike current therapies that often target hormone receptors or HER2 proteins, DAN-222 may work through a novel mechanism, potentially offering hope for patients who have developed resistance to existing options. Additionally, DAN-222 is administered intravenously, which could provide more controlled dosing compared to some oral treatments. The combination of DAN-222 with niraparib, a PARP inhibitor, is also being explored, which might enhance treatment effectiveness by attacking cancer cells through different pathways.

What evidence suggests that this trial's treatments could be effective?

Research has shown that DAN-222 may help treat solid tumors. In this trial, some participants will receive DAN-222 alone. In previous studies, 38% of patients experienced stable disease, meaning their cancer stopped growing temporarily. Other participants will receive a combination of DAN-222 with niraparib, a drug that improves outcomes in ovarian cancer. This combination increased the stable disease rate to 67% in earlier studies, suggesting it might be more effective. Niraparib alone has also slowed cancer growth in other types of cancer. These findings suggest that DAN-222, especially when combined with niraparib, could help manage metastatic breast cancer. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

A minimum of 2 weeks or 5 half-lives (whichever is longer) will be required from any prior therapy for mBC, including chemotherapy, immunotherapy and/or radiation therapy.

Subjects must have measurable disease as per RECIST v1.1.

Additional Inclusion Criteria for Stage 2: Documentation of DNA repair defects status validated from HRD plasma testing through the central laboratory or from archival tumor tissue or germ line testing. This testing will need to occur prior to enrollment.

Exclusion Criteria

Subject is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.

Subjects taking medications know to prolong the QT interval or associated with torsades de pointes, unless the subject can safely discontinue these medications or change to comparable medications that do not significantly prolong the QT interval, at least 5 half-lives or 7 days (whichever is longer) prior to the first dose of DAN-222.

Inability to comply with study procedures or unwilling to use adequate birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Dose escalation of single agent DAN-222 administered IV every week

8-12 weeks

Weekly visits (in-person)

Treatment Part B

Dose escalation of DAN-222 in combination with daily oral niraparib

8-12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DAN-222
• Niraparib

How Is the Trial Designed?

Group I: Dose Escalation (DAN-222) Experimental Treatment 1 Intervention

The starting dose of DAN-222 will be administered IV every week (QW) to subjects in the first cohort.

Group II: Dose Escalation (DAN-222 + niraparib) Experimental Treatment 2 Interventions

The starting dose of DAN-222 will be administered IV every week (QW), in combination with daily oral niraparib.

Who Is Running the Clinical Trial?

Dantari, Inc.

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

In a pilot study of 21 patients with localized HER2-negative, BRCA-mutated breast cancer, neoadjuvant treatment with niraparib showed a high tumor response rate of 90.5% after 2 cycles, indicating strong antitumor activity.

Among those who continued treatment for 2-6 cycles, 40% achieved a pathological complete response, and no new safety concerns were reported, suggesting that niraparib is both effective and safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer. Spring, LM., Han, H., Liu, MC., et al.[2022]

Niraparib, a PARP inhibitor for recurrent ovarian cancer, showed no significant changes in its pharmacokinetics when taken with a high-fat meal compared to fasting, indicating it can be safely taken with or without food.

The study demonstrated that niraparib was well-tolerated and had similar adverse events regardless of the meal condition, confirming its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer. Moore, K., Zhang, ZY., Agarwal, S., et al.[2019]

In a Phase 2 study involving 20 Japanese women with heavily pretreated ovarian cancer, niraparib demonstrated an objective response rate of 35%, indicating that it can effectively reduce tumor size in some patients.

The treatment was generally well-tolerated, with a high disease control rate of 90%, although common side effects included anemia and nausea, and 70% of patients experienced dose reductions or interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. Okamoto, A., Kondo, E., Nakamura, T., et al.[2021]

Niraparib, administered at doses of 200 mg and 300 mg daily, was found to be tolerable in Japanese patients with advanced solid tumors, with only one case of dose-limiting toxicity observed.

The study demonstrated a favorable pharmacokinetic profile for niraparib, with dose-proportional increases in drug levels and some patients showing a partial response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety, tolerability and pharmacokinetics of niraparib in Japanese patients with solid tumours: results of a phase I dose-escalation study. Yonemori, K., Shimizu, T., Kondo, S., et al.[2021]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Niraparib at a dose of 200 mg/day was determined to be the recommended phase 2 dose when combined with abiraterone acetate plus prednisone (AAP) for patients with metastatic castration-resistant prostate cancer (mCRPC), as it showed a tolerable safety profile with no new safety signals.

The combination of niraparib with apalutamide resulted in a higher incidence of dose-limiting toxicities, leading to the decision not to further evaluate this combination, highlighting the importance of monitoring drug interactions in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). Saad, F., Chi, KN., Shore, ND., et al.[2021]

Niraparib significantly extends progression-free survival in patients with newly diagnosed advanced ovarian cancer, showing efficacy in both homologous-recombination deficiency positive (HRd) and negative (HRp) populations, based on a phase III trial.

The treatment has a manageable safety profile, with myelosuppression as the main concern, which can be effectively managed through monitoring and individualized dosing based on weight and platelet count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. Lee, A.[2022]

In a Phase 2 study involving 19 Japanese patients with platinum-sensitive, relapsed ovarian cancer, niraparib at a dose of 300 mg/day was found to have a safety profile consistent with previous studies, with 31.6% of patients experiencing grade 3 or 4 thrombocytopenia-related events within 30 days of treatment.

The overall safety profile of niraparib was deemed acceptable, with common treatment-emergent adverse events including nausea and decreased blood cell counts, but no significant improvements in tumor response were observed in the small cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer. Takehara, K., Matsumoto, T., Hamanishi, J., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.1081

Efficacy of DAN-222, a novel investigational polymeric ... These data support continued development of DAN-222 to treat solid tumors and its combination use with PARP inhibitors. Open in Viewer ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05261269

NCT05261269 | A Dose-escalation Study of the Safety and ... This was an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and PK of IV administered DAN-222 followed by a ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO3-18-12/744983/Abstract-PO3-18-12-Results-from-a-first-in-human

Results from a first-in-human study of DAN-222, a novel high ... Furthermore, DAN-222 demonstrates reduced bone marrow exposure enabling clinical combinations. Herein we present data for the first-in-human ...

4. prnewswire.com prnewswire.com/news-releases/dantaris-novel-high-capacity-drug-conjugate-dan-222-shows-promising-antitumor-activity-in-patients-with-metastatic-her2-negative-breast-cancer-302005214.html

Dantari's Novel High-Capacity Drug Conjugate DAN-222 ... Results showed stable disease (SD) in 38% of participants receiving DAN-222 as monotherapy and SD in 67% of participants receiving DAN-222 in ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=ba92dc0b-7637-4cdf-83c3-72d01c13f595

DAN-222 / Dantari DAN-222 is a novel investigational polymeric nanoparticle conjugated with camptothecin, a topoisomerase I inhibitor, that provides significant accumulation of ...

6. withpower.com withpower.com/trial/phase-1-her2-negative-metastatic-breast-cancer-1-2022-2d97d

A Dose-escalation Study of the Safety and Pharmacology ... What safety data exists for Niraparib (also known as DAN-222 or Zejula)?. Niraparib has been studied for safety in various clinical trials, including those ...

7. synapse.patsnap.com synapse.patsnap.com/drug/7cccf499aab9498b800129ac5b7bfc45

DAN-222 - Drug Targets, Indications, Patents "These data on DAN-222 are encouraging as they show this novel platform with high chemotherapy capability was safe and well tolerated in heavily pretreated ...