Tiragolumab + Atezolizumab + Chemotherapy for Breast Cancer

No longer recruiting at 34 trial locations

Overseen By Reference Study ID Number: CO42177 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: Anthracyclines, Platinum, Taxanes

Disqualifiers: CNS disease, Leptomeningeal disease, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of cancer drugs to assess their safety and effectiveness in treating triple-negative breast cancer (TNBC), a type that doesn't respond to common hormone therapies. The study uses tiragolumab (an experimental treatment) and atezolizumab (Tecentriq, an immunotherapy drug), along with various chemotherapy drugs, to treat patients with early-stage or metastatic TNBC. Eligible participants have TNBC tumors that test positive for PD-L1 (a protein affecting the immune system), and in some cases, the cancer must be at least 2 centimeters in size. The trial aims to find better treatment options for those facing this aggressive form of breast cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC.

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

Research shows that tiragolumab, when combined with atezolizumab and chemotherapy, is under study for safety in treating triple-negative breast cancer. Although this specific combination is still under investigation, tiragolumab and atezolizumab have been studied separately in other research.

The FDA has already approved atezolizumab for other cancer types, indicating its safety is well understood. Previous studies on tiragolumab combined with atezolizumab found that people generally tolerate it well. Common side effects include tiredness and infusion reactions, which can be managed.

The chemotherapy drugs in this study, such as nab-paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, are standard treatments for breast cancer with well-known safety records. They can cause side effects like nausea and hair loss, typical with chemotherapy.

Overall, the current phase of this study focuses on understanding the safety of these combined treatments for people with triple-negative breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about tiragolumab in combination with atezolizumab for treating triple-negative breast cancer because it offers a fresh approach to tackling this aggressive cancer type. Unlike standard treatments that typically focus on chemotherapy alone, this combination leverages the immune system more effectively by pairing tiragolumab, an anti-TIGIT antibody, with atezolizumab, an anti-PD-L1 antibody. This dual immunotherapy approach aims to enhance the body's natural defenses against cancer, potentially leading to better outcomes. Additionally, the combination can be administered with chemotherapy agents like nab-paclitaxel, carboplatin, and others, which might improve overall efficacy compared to existing therapies.

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

Research has shown that using tiragolumab and atezolizumab with chemotherapy might be promising for treating triple-negative breast cancer (TNBC). In this trial, participants in Cohort A will receive tiragolumab and atezolizumab with nab-paclitaxel. Previous studies suggest that atezolizumab, when combined with nab-paclitaxel, helps the immune system fight cancer more effectively. Tiragolumab, which targets a different part of the immune system, may enhance this effect. Some early trials demonstrated that this combination can improve the body's response to the tumor. While more information is needed, these treatments together have shown potential in managing TNBC. ^{2 4 5 6 7}

Who Is on the Research Team?

Clinical Trial

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Inclusion Criteria

Metastatic or locally advanced unresectable, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression

Only patients with metastatic TNBC tumors that are centrally tested and found to be programmed death-ligand 1 (PD-L1) positive will be enrolled

No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tiragolumab and atezolizumab in combination with chemotherapy

5 months

Day 1 of Cycles 1-5

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Cyclophosphamide
• Doxorubicin
• Nab-paclitaxel
• Tiragolumab

How Is the Trial Designed?

Group I: Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Experimental Treatment 8 Interventions

Participants with early TNBC in the neoadjuvant setting, who are eligible for surgery, will receive tiragolumab and atezolizumab every 2 weeks (Q2W) in combination with nab-paclitaxel weekly (QW) and carboplatin every 3 weeks (Q3W) for four cycles, followed by tiragolumab and atezolizumab in combination with doxorubicin and cyclophosphamide Q2W with granulocyte colony-stimulating factor (G-CSF; filgrastim or pegfilgrastim) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support for four doses.

Group II: Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Experimental Treatment 7 Interventions

Participantswith early TNBC in the neoadjuvant setting, who are eligible for surgery, will receive tiragolumab and atezolizumab Q2W in combination with nab-paclitaxel QW for 12 weeks, followed by tiragolumab and atezolizumab in combination with doxorubicin and cyclophosphamide Q2W with G-CSF (filgrastim or pegfilgrastim) or GM-CSF support for four doses.

Group III: Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel Experimental Treatment 3 Interventions

Participants with first-line metastatic TNBC will receive tiragolumab and atezolizumab on Day 1 of every 28-day cycle plus nab-paclitaxel on Days 1, 8, and 15 of every 28-day cycle.

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Caelyx/Doxil, a pegylated liposomal formulation of doxorubicin, has a unique pharmacokinetic profile that allows it to effectively target tumor sites while reducing toxicity compared to traditional doxorubicin.

It has been approved by the FDA and EMEA for treating AIDS-related Kaposi's sarcoma and recurrent epithelial ovarian cancer, and is being investigated for use in various other cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Tejada-Berges, T., Granai, CO., Gordinier, M., et al.[2022]

In a phase I study involving 26 patients with advanced solid tumors, the combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel was found to be feasible, with a maximum tolerated dose established at 15 mg/m2 for Caelyx and 115 mg/m2 for paclitaxel, administered every two weeks.

The treatment regimen showed acceptable toxicity levels, with mild hematologic side effects and no significant cardiotoxicity, while achieving a complete response in one patient and partial responses in four, particularly among breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. Mavroudis, D., Kouroussis, Ch., Kakolyris, S., et al.[2018]

The study found that the excipient Cremophor® EL (CrEL) in the conventional paclitaxel formulation (Taxol®) causes red blood cell (RBC) lysis and other harmful effects, which could lead to complications for patients, especially those with blood disorders.

In contrast, the nanoparticle albumin-bound paclitaxel (Abraxane®) did not cause these adverse effects on RBCs, highlighting that the choice of excipients can significantly impact the safety and efficacy of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxol(®)-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor(®) EL. Vader, P., Fens, MH., Sachini, N., et al.[2015]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

The combination of pemetrexed and nab-paclitaxel was found to be feasible and well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with a recommended phase II dose established at pemetrexed 500 mg/m² and nab-paclitaxel 260 mg/m².

In a phase II trial involving 37 patients, the treatment showed a response rate of 14% and a disease control rate of 46%, with a median overall survival of 8.8 months, indicating some efficacy in second and third-line therapy despite the early closure of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Ho, C., Davies, AM., Sangha, RS., et al.[2023]

In a phase II clinical trial involving 55 patients with operable breast cancer, preoperative chemotherapy using nanoparticle albumin-bound paclitaxel (nab-PTX) followed by an epirubicin and cyclophosphamide regimen achieved a pathological complete response (pCR) rate of 22.2%, indicating its efficacy in treating this condition.

The study found that HER2-positive patients had a significantly higher pCR rate of 60%, suggesting that HER2 status is an important factor in predicting treatment response, while the overall safety profile of the treatment was considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. Futamura, M., Nagao, Y., Ishihara, K., et al.[2018]

The study developed an aptamer-drug conjugate (ApDC) that targets the HER3 receptor, showing improved delivery and efficacy of doxorubicin (DOX) in tumor-bearing mice compared to traditional liposomal and free DOX.

This targeted approach not only enhanced tumor suppression but also reduced toxic side effects, such as weight loss and organ damage, indicating better tolerability for patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aptamer-drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity. Dou, XQ., Wang, H., Zhang, J., et al.[2022]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

Liposomal formulations of anthracycline antibiotics, like Doxil and DaunoXome, improve the pharmacokinetics of these drugs, leading to longer circulation times and reduced toxicity compared to their free forms.

These liposomal formulations are effective in treating certain cancers, such as AIDS-related Kaposi's sarcoma, and their design allows for enhanced uptake by tumor cells when coupled with monoclonal antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Liposomal formulations of anthracycline antibiotics]. Berezov, TT., Iaglova, NV., Chekhonin, VP., et al.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06175390

Study Details | NCT06175390 | Tiragolumab, Atezolizumab ... Patients will receive neoadjuvant therapy with four cycles of 1200 mg of atezolizumab and 600 mg of Tiragolumab every 3 weeks in combination with nab-paclitaxel ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P2-12-23/754103/Abstract-P2-12-23-A-phase-2-trial-combining

Abstract P2-12-23: A phase 2 trial combining tiragolumab and ... SKYLINE is a phase 2 trial exploring the use of an anti-TIGIT therapy, tiragolumab, in combination with anti PD-L1 atezolizumab and chemotherapy ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04584112?id=%22NCT03197935%22OR%22NCT04584112%22&rank=1

NCT04584112 | A Study of the Safety, Efficacy, and ... The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of tiragolumab in combination with atezolizumab and chemotherapy

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10320476/

Facts and Hopes in Immunotherapy for Early-Stage Triple- ... PD-L1 Immunohistochemistry assay comparison in atezolizumab plus nab-paclitaxel-treated advanced triple-negative breast cancer. J Natl Cancer Inst. 2021;113 ...

5. genentech-clinicaltrials.com genentech-clinicaltrials.com/content/patient-platform/na/us/en/trials/cancer/bc/a-study-of-the-safety--efficacy--and-pharmacokinetics-o-75095.pdf

A clinical trial to look at how well tiragolumab plus ... Combination With Atezolizumab and Chemotherapy in Patients With Triple-Negative Breast Cancer ... trial will also look at how effective the combination is ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT04584112

NCT04584112 Duration of Response (Cohort A), Up to approximately 21 months ; Overall Survival (Cohort A), Up to approximately 21 months ; Serum Concentrations of Tiragolumab ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bc/a-study-of-the-safety--efficacy--and-pharmacokinetics-o-75095.html

Clinical Trial – Breast Cancer – Safety, Efficacy, and Ph... A clinical trial to look at how well tiragolumab plus atezolizumab and chemotherapy worked to treat triple‑negative breast cancer