Targeted Therapy for Triple Negative Breast Cancer

(PERSEVERE Trial)

No longer recruiting at 14 trial locations

Overseen By Rae Richards

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bryan Schneider, MD

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: Stage IV disease, Active second malignancy, Uncontrolled disease, Severe allergies, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Determined by treating physician

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with triple-negative breast cancer, a type that does not respond to hormonal or HER2-targeted therapies. Researchers aim to evaluate the effectiveness of these treatments based on specific markers in the blood and tumor DNA, which guide treatment decisions. The study includes three groups: one uses targeted therapies (including Atezolizumab, an immunotherapy drug, and Inavolisib, an experimental treatment), another provides a treatment chosen by doctors if certain markers are absent, and the last group also allows doctors to select the treatment for patients without these markers. This trial seeks patients who have completed chemotherapy before surgery but still have significant cancer remaining. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking pembrolizumab, there is a 3-week period without it before starting the study treatment for those in Arm 1. You may continue pembrolizumab during the study for Arms 2 and 3, based on the investigator's discretion.

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

Research has shown that talazoparib, when combined with capecitabine, is generally manageable for patients. In past studies, common side effects included tiredness, low red blood cell count, and nausea, affecting more than 20% of patients. Despite these side effects, the FDA has approved talazoparib for certain types of breast cancer, indicating a well-understood safety profile.

For the combination of inavolisib and capecitabine, studies have found it to be as safe as other breast cancer treatments. Inavolisib has undergone long-term testing and demonstrated consistent safety over time. Most patients tolerated the treatment well, similar to other hormone-related therapies.

In summary, both treatment options have known side effects but are generally well-tolerated according to previous research. This suggests a reasonable level of safety for participants considering joining the clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments being studied for triple-negative breast cancer because they target specific genetic pathways that current standard treatments do not. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, these treatments use targeted therapy and immunotherapy to zero in on cancer cells with precision. For example, talazoparib is a PARP inhibitor that exploits DNA repair weaknesses in cancer cells, while inavolisib targets the PI3K pathway, crucial for cancer cell growth and survival. Additionally, the combination of these drugs with capecitabine and pembrolizumab—an immunotherapy agent—may offer a more tailored approach, potentially improving outcomes for patients with specific genomic profiles.

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

Research has shown that talazoparib, one of the treatments in this trial, yields promising results for breast cancer patients with BRCA mutations. Specifically, 5.5% of patients achieved a complete response, and 57.1% had a partial response. Other studies have found a 50% response rate, with many patients benefiting from the treatment. In this trial, some participants will receive talazoparib in combination with other therapies.

Inavolisib, another treatment option in this trial, has also demonstrated positive results. Studies of breast cancer with PIK3CA mutations showed that it significantly improved overall survival when combined with other treatments. It notably doubled the time patients lived without the cancer worsening compared to a placebo. Participants in this trial may receive inavolisib as part of their treatment regimen.

Both treatments hold potential for treating breast cancer. Talazoparib aids in DNA repair, while inavolisib targets specific genetic mutations. ^{5 6 7 8 9}

Who Is on the Research Team?

Bryan P Schneider, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for women with residual Triple Negative Breast Cancer (TNBC) after pre-op therapy. They must have completed neoadjuvant chemotherapy and surgery, not be pregnant, and agree to use contraception. Excluded are those with chronic hepatitis B, uncontrolled diseases, recent investigational drug use, certain eye conditions or diabetes requiring treatment, active second malignancy other than specific skin/prostate cancer types, HIV without undetectable viral load in the past 6 months, recent heart issues or severe allergies to study meds.

Inclusion Criteria

I need radiotherapy after my breast-conserving surgery unless my doctor advises against it.

I am willing to use effective birth control during the study.

My breast cancer is confirmed to be triple negative.

Exclusion Criteria

You have had strong allergic reactions to the study medications before.

I have chronic hepatitis B with an undetectable viral load in the last 6 months.

I have diabetes and am currently on treatment, or I have Type 1 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment based on plasma ctDNA status and genomic markers, including options such as talazoparib, capecitabine, pembrolizumab, and inavolisib

Determined by treating physician

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of overall survival and disease-free survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Capecitabine
• Inavolisib
• Talazoparib

Trial Overview The study tests three treatments based on plasma ctDNA positivity and genomic markers: Pembrolizumab (an immunotherapy), Capecitabine (a chemotherapy drug), Talazoparib and Inavolisib (targeted therapies). Patients will be stratified into one of these three arms depending on their individual tumor DNA characteristics.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 4 Interventions

Arm 1a: Patients who are ctDNA-positive and harbor a genomic target. DNA repair pathway = talazoparib + capecitabine (CLOSED) Arm 1b: Patients who are ctDNA-positive and harbor a genomic target. Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED) Arm 1c: Patients who are ctDNA-positive and harbor a genomic target. PI3K Pathway = inavolisib + capecitabine ---\> +/- standard of care pembrolizumab Arm 1d: Patients who are ctDNA-positive and harbor a genomic target. DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab

Group II: Arm 2 Active Control 2 Interventions

Arm 2 subjects have plasma ctDNA positive but do not have a genomically driven treatment option. Treatment of physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician.

Group III: Arm 3 Active Control 2 Interventions

Arm 3 subjects have plasma ctDNA negative. Treatment of patient and physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Bryan Schneider, MD

Lead Sponsor

Trials

2

Recruited

390+

Vera Bradley Foundation for Breast Cancer

Collaborator

Trials

2

Recruited

390+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Foundation Medicine

Industry Sponsor

Trials

37

Recruited

17,600+

Indiana University

Collaborator

Trials

1,063

Recruited

1,182,000+

Epic Sciences

Industry Sponsor

Trials

7

Recruited

6,600+

Vera Bradley Foundation for Breast Cancer Research

Collaborator

Trials

1

Recruited

200+

Published Research Related to This Trial

In a phase 3 trial involving 902 patients with metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel showed a median overall survival of 21.0 months compared to 18.7 months with placebo, although this difference was not statistically significant in the overall population.

For patients with PD-L1 immune cell-positive tumors, atezolizumab plus nab-paclitaxel demonstrated a significant overall survival benefit, with a median survival of 25.0 months versus 18.0 months for placebo, highlighting its potential as an important treatment option for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Schmid, P., Rugo, HS., Adams, S., et al.[2020]

The combination of the PD-L1 inhibitor atezolizumab with standard chemotherapy significantly improves overall survival in patients with metastatic triple-negative breast cancer compared to chemotherapy alone.

This research suggests that adding atezolizumab could provide a new treatment option for patients suffering from this aggressive form of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitor Improves Survival in TNBC. [2019]

In a subgroup analysis of 36 Japanese patients with early-stage triple-negative breast cancer, adding atezolizumab to chemotherapy showed a numerical improvement in pathological complete response (41% vs. 37% in the placebo group), aligning with global study results.

The safety profile was consistent with previous findings, as treatment-related grade 3-4 adverse events occurred in 71% of the atezolizumab group and 68% of the placebo group, with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analysis of Japanese patients in a phase III randomized, controlled study of neoadjuvant atezolizumab or placebo, combined with nab-paclitaxel and anthracycline-based chemotherapy in early triple-negative breast cancer (IMpassion031). Saji, S., Ohsumi, S., Ito, M., et al.[2022]

Atezolizumab, a PD-L1 inhibitor, has received accelerated approval from the FDA for treating PD-L1-positive metastatic triple-negative breast cancer (TNBC), showing significant improvements in progression-free survival when combined with nab-paclitaxel in the IMpassion130 trial.

The ongoing Phase III IMpassion132 trial is further evaluating atezolizumab combined with first-line chemotherapy in patients with inoperable locally advanced/metastatic TNBC, with overall survival as the primary endpoint, indicating a focus on long-term treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMpassion132 Phase III trial: atezolizumab and chemotherapy in early relapsing metastatic triple-negative breast cancer. Cortés, J., André, F., Gonçalves, A., et al.[2022]

Talazoparib-loaded solid lipid nanoparticles (BMN 673-SLNs) demonstrated significant cytotoxic effects against BRCA1 deficient Triple Negative Breast Cancer (TNBC) cell lines, showing higher apoptotic rates compared to the free drug BMN 673, indicating enhanced therapeutic potential.

BMN 673-SLNs exhibited improved stability and reduced toxicity to normal cells (MCF-10A) while maintaining efficacy against resistant cancer cells, suggesting a promising strategy for targeting drug-resistant TNBC with minimized side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro. Eskiler, GG., Cecener, G., Dikmen, G., et al.[2020]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

Citations

1. roche.com roche.com/media/releases/med-cor-2025-05-31

New data show Roche's Itovebi significantly extended ... These data showed Itovebi TM (inavolisib), in combination with palbociclib (Ibrance®) and fulvestrant, reduced the risk of death by more than 30% compared with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40454641/

Overall Survival with Inavolisib in PIK3CA-Mutated ... Treatment with inavolisib plus palbociclib-fulvestrant led to a significant overall survival benefit, as compared with placebo plus ...

3. nejm.org nejm.org/doi/10.1056/NEJMoa2404625

Inavolisib-Based Therapy in PIK3CA-Mutated Advanced ... The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1108

Enhanced efficacy of inavolisib combined with anti-PD-1 or ... Conversely, the combination of Inavolisib and PD-1 antibody significantly prolonged overall survival in triple-negative breast cancer mice. In ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT363596

Long-term safety of inavolisib (GDC-0077) in an ongoing ... Conclusions: These data indicate acceptable long-term tolerability. The safety profile of pts on study treatment with inavolisib alone or in combo with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04849364?term=INAVOLISIB&rank=9

Study Details | NCT04849364 | Circulating Tumor DNA ... This is a 3-arm study stratified by plasma ctDNA. Patients with residual TNBC disease after pre-operative therapy will be assigned to 1 of 3 Arms based on ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bc/a-study-evaluating-the-efficacy-and-safety-of-gdc-0077--75564.html

Clinical study / inavolisib in Breast Cancer | ForPatient... This study is testing a medicine called inavolisib, combined with standard treatment. It is being developed to treat PIK3CA-mutated, HR-positive, HER2-negative ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9300946/

Efficacy and Safety of Capecitabine for Triple-Negative ... The addition of capecitabine to early-stage TNBC patients receiving standard adjuvant chemotherapy showed significant DFS and OS improvement with tolerable ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/219249Orig1s000MultidisciplineR.pdf

219249Orig1s000 - accessdata.fda.gov Therefore, it is important to evaluate data further characterizing the efficacy and safety of inavolisib for the treatment of breast cancer in study.