A Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Participants With Triple-Negative Breast Cancer

Recruiting at 24 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

83 Participants Needed

Trial Summary

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.

What data supports the effectiveness of this drug combination?

Research shows that nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined with carboplatin is effective in treating advanced non-small-cell lung cancer (NSCLC). Additionally, nab-paclitaxel has been found to be effective and less toxic for breast cancer treatment compared to other formulations. ^{1 2 3 4 5}

What safety data exists for nanoparticle albumin-bound paclitaxel (Abraxane)?

Nanoparticle albumin-bound paclitaxel (Abraxane) is generally considered safer than solvent-based paclitaxel because it avoids severe allergic and hypersensitivity reactions associated with the solvent. However, it can still cause side effects like peripheral neuropathy (nerve damage), myalgias (muscle pain), and neutropenia (low white blood cell count). ^{6 7 8 9 10}

What makes this drug combination unique compared to other treatments?

This drug combination is unique because it includes a mix of chemotherapy drugs like Atezolizumab and Tiragolumab, which are immune checkpoint inhibitors that help the immune system fight cancer, along with traditional chemotherapy agents like Carboplatin, Cyclophosphamide, Doxorubicin, and Nab-paclitaxel. The combination aims to enhance the effectiveness of treatment by using different mechanisms to target cancer cells. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial is testing a new combination of two drugs and chemotherapy for patients with a hard-to-treat type of breast cancer. The goal is to boost the immune system's ability to fight the cancer while also killing the cancer cells directly.

Research Team

Clinical Trial

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

Interventions

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

Participant Groups

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

Findings from Research

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]

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]

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 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 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]

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]

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]

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]

References

1. United States 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. [2022]

2. England 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. [2022]

3. United States 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. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Efficacy and Safety of Upfront Weekly Nanoparticle Albumin-bound Paclitaxel for HER2-negative Breast Cancer. [2017]

5. Japan 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. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Adverse event profiles of solvent-based and nanoparticle albumin-bound paclitaxel formulations using the Food and Drug Administration Adverse Event Reporting System. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Species difference in paclitaxel disposition correlated with poor pharmacological efficacy translation from mice to humans. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Taxol(®)-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor(®) EL. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel in cancer treatment: perspectives and prospects of its delivery challenges. [2022]

11. Switzerland 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. [2018]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Liposomal formulations of anthracycline antibiotics]. [2014]

13. England pubmed.ncbi.nlm.nih.gov

Lung cancer combination therapy: co-delivery of paclitaxel and doxorubicin by nanostructured lipid carriers for synergistic effect. [2022]

14. New Zealand pubmed.ncbi.nlm.nih.gov

Aptamer-drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity. [2022]

15. England pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. [2022]