OKI-219 for Breast Cancer

(PIKture-01 Trial)

Recruiting at 39 trial locations

Overseen By OnKure, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: OnKure, Inc.

Must be taking: GnRH agonists

Must not be taking: Corticosteroids, PPIs

Disqualifiers: Diabetes, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 weeks for dose escalation and optimization

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called OKI-219 for breast cancer and other advanced solid tumors. Researchers aim to determine the safety and effectiveness of OKI-219 both alone and in combination with other cancer drugs. The study will explore different doses to identify the optimal one. Individuals with advanced solid tumors, particularly those with a specific gene mutation (PI3KαH1047R) and certain types of breast cancer, may be suitable candidates. Participants should have managed their condition for some time and tried other treatments previously. As a Phase 1 trial, this research focuses on understanding how OKI-219 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 use proton pump inhibitors, certain enzyme inhibitors or inducers, or specific drug transporter substrates within one week before starting the study drug.

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

A previous study found that OKI-219 was well tolerated at all dose levels. Participants did not experience high blood sugar, and only mild side effects, classified as grade 1, were reported. These side effects were not serious and posed no significant risk.

Separate safety data for combinations with other drugs like tucatinib, trastuzumab, fulvestrant, atirmociclib, and ribociclib is not available. However, the overall safety of OKI-219 in humans appears promising. As the study is in an early phase, the main goal is to test safety and how the body processes the drug. This ongoing research aims to ensure the treatment remains safe when combined with other cancer drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about OKI-219 because it targets the PI3KαH1047R mutation, a specific genetic alteration found in certain breast cancers. Unlike standard treatments like hormone therapy, chemotherapy, or HER2-targeted therapies, OKI-219 is developed to work alongside other drugs, such as Tucatinib, Trastuzumab, Fulvestrant, and CDK4/6 inhibitors like Atirmociclib and Ribociclib, to enhance their effectiveness. This approach aims to offer a more tailored and potentially more effective treatment option for patients with advanced, hard-to-treat breast cancers that exhibit this mutation.

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

Studies have shown that OKI-219 might help treat breast cancer, particularly in patients with the PI3KαH1047R genetic mutation. Research suggests that OKI-219 can target tumors unresponsive to other standard treatments. Early results indicate that OKI-219 is generally well tolerated, with few side effects. In this trial, participants will receive OKI-219 either as a monotherapy or combined with other treatments. Some arms will test OKI-219 with fulvestrant, while others will combine it with trastuzumab and tucatinib. These combinations may enhance the therapies' effectiveness. These findings suggest that OKI-219 could be a promising option for treating certain types of advanced breast cancer. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, especially breast cancer, that have specific genetic mutations or no standard treatment options. Breast cancer patients must have tried certain therapies unless contraindicated. Participants need a tumor suitable for biopsy and agree to ovarian suppression if needed.

Inclusion Criteria

My condition matches the specific requirements for this study's phase and group.

Participants must have at least 1 measurable lesion based on RECIST version 1.1

I can swallow and tolerate pills.

Exclusion Criteria

History of symptomatic drug-induced pneumonitis

Positive hepatitis B virus (HBV) core antibody or hepatitis C virus (HCV) antibody

I have heart problems or significant heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OKI-219 as monotherapy or in combination with fulvestrant or trastuzumab, with dose escalation and optimization phases

Up to 28 weeks for dose escalation and optimization

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and pharmacokinetics

30 days after last dose

Long-term Follow-up

Participants are monitored for progression-free survival and other long-term outcomes

Up to approximately 36 months

What Are the Treatments Tested in This Trial?

Interventions

• OKI-219

Trial Overview The study tests OKI-219 alone and combined with fulvestrant or trastuzumab in escalating doses to assess safety, tolerability, and effectiveness. Part A studies OKI-219 solo; Parts B & C test it with the other drugs at doses found safe in Part A until disease progression or unacceptable side effects occur.

How Is the Trial Designed?

Group I: Phase 1b: Part E Dose Expansion Experimental Treatment 3 Interventions

OKI-219 + Fulvestrant + Ribociclib Dose Expansion in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group II: Phase 1b: Part E Dose Escalation Experimental Treatment 3 Interventions

OKI-219 + Fulvestrant + Ribociclib Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group III: Phase 1b: Part D Dose Expansion Experimental Treatment 3 Interventions

OKI-219 + Fulvestrant + Atirmociclib Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group IV: Phase 1b: Part D Dose Escalation Experimental Treatment 3 Interventions

OKI-219 + Fulvestrant + Atirmociclib Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group V: Phase 1b: Part C Dose Expansion Experimental Treatment 3 Interventions

OKI-219 + Tucatinib + Trastuzumab Dose Expansion in participants with HR±/HER2+ locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group VI: Phase 1b: Part C Dose Escalation Experimental Treatment 3 Interventions

OKI-219 + Tucatinib + Trastuzumab Dose Escalation in participants with HR±/HER2+ locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group VII: Phase 1b: Part B Dose Optimization Experimental Treatment 2 Interventions

OKI-219 + Fulvestrant Dose Optimization in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group VIII: Phase 1b: Part B Dose Escalation Experimental Treatment 2 Interventions

OKI-219 + Fulvestrant Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation

Group IX: Phase 1a: Part A Dose Escalation Experimental Treatment 1 Intervention

OKI-219 Monotherapy Dose Escalation in participants with advanced solid tumors with the PI3KαH1047R mutation

Who Is Running the Clinical Trial?

OnKure, Inc.

Lead Sponsor

Trials

3

Recruited

220+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06239467

NCT06239467 | First-in-Human Study of OKI-219 ... OKI-219 + Fulvestrant Dose Escalation in participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer with the PI3KαH1047R mutation.

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P3-08-19/752177/Abstract-P3-08-19-Preliminary-results-from-PIKture

Abstract P3-08-19: Preliminary results from PIKture-01, a First ... Phase 1b will assess OKI-219 in combination with fulvestrant in patients with HR+ breast cancer, or with trastuzumab in patients with HER2+ ...

3. investors.onkuretherapeutics.com investors.onkuretherapeutics.com/news-releases/news-release-details/onkure-announces-encouraging-preliminary-safety-tolerability-and

Release Details OKI-219 was well tolerated across all dose levels with no hyperglycemia, and only grade 1 treatment-related adverse events (TRAEs) were reported.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/456777

First-in-Human Study of OKI-219 in Advanced Solid ... OKI-219-101 is a Phase 1a/1b, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics ...

5. globenewswire.com globenewswire.com/news-release/2024/12/10/2994355/0/en/OnKure-Announces-Encouraging-Preliminary-Safety-Tolerability-and-Pharmacokinetic-PK-Data-from-its-First-In-Human-PIKture-01-Trial-of-OKI-219.html

OnKure Announces Encouraging Preliminary Safety, OKI-219 was well tolerated across all dose levels with no hyperglycemia, and only grade 1 treatment-related adverse events (TRAEs) were reported.

6. investors.onkuretherapeutics.com investors.onkuretherapeutics.com/static-files/70aad19f-5b65-4706-ad20-6cc2bda2d892

Corporate Overview This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth ...

7. cancer.gov cancer.gov/clinicaltrials/NCI-2024-01328

First-in-Human Study of OKI-219 in Advanced Solid ... OKI-219-101 is a Phase 1a/1b, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), ...