Combination Therapies for Breast Cancer

(Morpheus-panBC Trial)

Recruiting at 29 trial locations

Overseen By Reference Study ID Number: CO40115 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Antibiotics

Disqualifiers: Autoimmune disease, CNS metastases, 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: 21

580 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer. The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in parallel in this study: Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \[1L\] PD-L1+ cohort). Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \[2L\] CIT-naive cohort). Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative disease with PIK3CA mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (HR+cohort). Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort). In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). In addition, participants in the 2L CIT-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination (Stage 2), provided Stage 2 is open for enrollment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as investigational therapies, biologic treatments, and systemic immunosuppressive medications, at least 2 weeks prior to the study. It's best to discuss your specific medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug combination therapies for breast cancer?

The combination of atezolizumab (Tecentriq) with nab-paclitaxel has shown to significantly prolong progression-free survival in patients with advanced triple-negative breast cancer, according to the phase III IMpassion130 trial. This suggests that the combination therapy can be effective in treating this type of breast cancer. ^{1 2 3 4 5}

Is the combination therapy for breast cancer generally safe for humans?

Research shows that eribulin and capecitabine, when used in combination with other treatments, are generally well-tolerated in breast cancer patients, with minimal side effects like myelosuppression (low blood cell counts) and alopecia (hair loss). ^{2 6 7 8 9}

What makes this drug combination unique for breast cancer treatment?

This combination therapy is unique because it includes atezolizumab, an immunotherapy drug that targets PD-L1, and is the first of its kind approved for advanced triple-negative breast cancer when used with nab-paclitaxel. This approach leverages the immune system to fight cancer, offering a novel mechanism compared to traditional chemotherapy. ^{3 4 9 10 11}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with metastatic or locally advanced breast cancer, including those who haven't had systemic therapy for TNBC, have progressed after first-line chemo, or have HR+/HER2- disease with PIK3CA mutation. Participants must be able to take capecitabine and agree to contraception if of childbearing potential. They should not have received certain prior treatments and must meet specific health criteria.

Inclusion Criteria

I haven't had any systemic treatment for my advanced triple-negative breast cancer.

My cancer is HER2 positive or low, and my blood sugar levels are within normal limits.

Your blood sugar levels are within a certain range when fasting and your HbA1c level is not too high.

Exclusion Criteria

I do not meet the exclusion criteria for Stage 1.

You have or had a condition where your immune system attacks your own body, or your immune system doesn't work properly.

Eligibility only for the control arm

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage 1

Participants are assigned to one of several treatment arms based on their cohort and receive treatment until unacceptable toxicity or disease progression

Variable, based on individual response

Regular visits as per treatment cycle (21 or 28 days)

Treatment Stage 2

Participants in the 2L CIT-naïve cohort who experience disease progression or loss of clinical benefit during Stage 1 may continue treatment with a different combination

Variable, based on individual response

Follow-up

Participants are monitored for safety and effectiveness after treatment

120 days after last dose

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• Capecitabine
• Gemcitabine + Carboplatin or Eribulin
• Ipatasertib
• Nab-Paclitaxel
• Sacituzumab Govitecan
• Selicrelumab
• SGN-LIV1A
• Tocilizumab

Trial Overview The study tests various treatment combinations (chemotherapy, targeted drugs like Inavolisib and Ribociclib, immunotherapies such as Atezolizumab) in four different patient cohorts based on their type of breast cancer and previous treatments. It's a two-stage trial where patients may switch treatments if they don't benefit from the initial one.

Participant Groups

Group I: Inavolisib + Ribociclib (dose #2) + Letrozole Experimental Treatment 3 Interventions

Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Group II: Inavolisib + Ribociclib (dose #2) + Fulvestrant Experimental Treatment 3 Interventions

Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Group III: Inavolisib + Ribociclib (dose #1) + Letrozole Experimental Treatment 3 Interventions

Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Group IV: Inavolisib + Ribociclib (dose #1) + Fulvestrant Experimental Treatment 2 Interventions

Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Group V: Inavolisib + Abemaciclib + Letrozole Experimental Treatment 2 Interventions

Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Group VI: Inavolisib + Abemaciclib + Fulvestrant Experimental Treatment 3 Interventions

Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Group VII: Inavolisib (dose #2) + Trastuzumab Deruxtecan Experimental Treatment 1 Intervention

HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Group VIII: Inavolisib (dose #1) + Trastuzumab Deruxtecan Experimental Treatment 2 Interventions

HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Group IX: Atezolizumab + Selicrelumab + Bevacizumab Experimental Treatment 3 Interventions

2L-CIT-naive participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.

Group X: Atezolizumab + Sacituzumab Govitecan Experimental Treatment 2 Interventions

1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.

Group XI: Atezolizumab + SGN-LIV1A Experimental Treatment 2 Interventions

2L CIT-naive participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.

Group XII: Atezolizumab + Nab-Paclitaxel + Tocilizumab Experimental Treatment 3 Interventions

1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.

Group XIII: Atezolizumab + Ipatasertib Experimental Treatment 2 Interventions

2L CIT-naive participants will receive doublet combination treatment with atezolizumab + ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.

Group XIV: Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin) Experimental Treatment 2 Interventions

2L CIT-naive participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naive participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemotherapy (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.

Group XV: Capecitabine Active Control 1 Intervention

2L CIT-naive participants will receive capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.

Group XVI: Atezolizumab + Nab-Paclitaxel Active Control 2 Interventions

1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab + nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.

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

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

In a study of 29 patients with HER2-positive operable breast cancer, the combination of nab-paclitaxel and trastuzumab followed by FEC resulted in a high pathological complete response (pCR) rate of 74.0%, indicating strong efficacy in the neoadjuvant chemotherapy setting.

The treatment was generally well tolerated, with sensory neuropathy being the most common side effect; however, severe grade 3 neuropathy occurred in only 3.4% of patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Trastuzumab Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide for HER2-positive Operable Breast Cancer: A Multicenter Phase II Trial. Tokunaga, S., Takashima, T., Kashiwagi, S., et al.[2019]

In a study involving 58 patients with recurrent HER2-negative breast cancer, eribulin showed a median progression-free survival (PFS) of 6.6 months compared to 4.2 months for treatment of physician's choice (TPC), suggesting a potential benefit in delaying disease progression.

Although eribulin demonstrated improved median time to treatment failure (TTF) of 6.0 months versus 3.6 months for TPC, these differences were not statistically significant, indicating that further studies are necessary to confirm the efficacy of eribulin in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical usefulness of eribulin as first- or second-line chemotherapy for recurrent HER2-negative breast cancer: a randomized phase II study (JBCRG-19). Aogi, K., Watanabe, K., Kitada, M., et al.[2022]

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]

Combination therapies using paclitaxel with other antineoplastic agents show promise for treating metastatic breast cancer, but optimal dosing and scheduling remain unclear, which complicates their development.

Unexpected toxic interactions between paclitaxel and other drugs have been observed, highlighting the need for careful evaluation of combination therapies in clinical trials before they are used outside of research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review. Holmes, FA.[2015]

In the IMpassion131 trial involving 651 patients with advanced triple-negative breast cancer, adding atezolizumab to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS) compared to paclitaxel alone, indicating that this combination may not provide the expected benefits in treatment outcomes.

While the addition of atezolizumab showed a higher unconfirmed overall response rate and longer duration of response in the PD-L1-positive population, the overall survival results were similar between the two treatment groups, suggesting that the combination therapy does not significantly enhance long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Miles, D., Gligorov, J., André, F., et al.[2021]

In a study involving 55 women with metastatic breast cancer, the combination of weekly paclitaxel and capecitabine resulted in a 55% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally tolerable, with a clinical benefit rate of 65% and a median duration of response of 10 months, although some patients experienced notable side effects like hand-foot skin reactions and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. Blum, JL., Dees, EC., Chacko, A., et al.[2015]

Capecitabine is a well-tolerated treatment for metastatic breast cancer, showing minimal side effects like myelosuppression and hair loss, which makes it a promising option for combination therapies with other anticancer drugs.

Ongoing phase II/III trials are investigating the use of capecitabine in early breast cancer treatment, and preliminary results indicate that it may provide significant benefits when used as part of adjuvant and neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. Fumoleau, P., Cameron, D.[2019]

This phase III study will evaluate the non-inferiority of eribulin, a non-taxane microtubule inhibitor, compared to taxanes in combination with trastuzumab and pertuzumab for treating HER2-positive metastatic breast cancer in 480 Japanese women.

The primary goal is to assess progression-free survival, with the potential for eribulin to become a safer alternative to taxanes if proven equally effective, addressing safety concerns associated with taxane-induced toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first-line or second-line treatment for HER2-positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non-inferiority, phase III trial in Japan (JBCRG-M06/EMERALD). Yamashita, T., Masuda, N., Saji, S., et al.[2021]

In a study of 40 patients with HER2-positive metastatic breast cancer, the combination of trastuzumab, paclitaxel, and capecitabine resulted in a high overall response rate of 81.1%, with 24.3% achieving complete responses and 56.8% partial responses.

The treatment was well-tolerated, with manageable grade 3 adverse events, indicating that this combination therapy is both effective and safe for first-line treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer. Tonyali, O., Benekli, M., Berk, V., et al.[2021]

Atezolizumab, when used with nab-paclitaxel for treating triple negative breast cancer, can cause rare side effects like autoimmune hemolytic anemia, as seen in a case study of a 59-year-old female patient.

The patient's hemolytic anemia was effectively managed with a high-dose prednisone taper, allowing her to continue her cancer treatment without further complications through multiple cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. Younce, CM., Lawton, JM., Patel, DR.[2021]

Capecitabine, an oral chemotherapy drug, has shown improved disease-free and overall survival when combined with docetaxel in advanced breast cancer, leading to further exploration of its combinations with other agents.

The combination of capecitabine with docetaxel and epirubicin (TEX) has demonstrated promising results and manageable toxicity, and is currently being evaluated in phase III trials for advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New directions with capecitabine combinations in advanced breast cancer. Budman, DR.[2015]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Trastuzumab Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide for HER2-positive Operable Breast Cancer: A Multicenter Phase II Trial. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

Clinical usefulness of eribulin as first- or second-line chemotherapy for recurrent HER2-negative breast cancer: a randomized phase II study (JBCRG-19). [2022]

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

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

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

Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. [2021]

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

Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. [2015]

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

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. [2019]

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

Trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first-line or second-line treatment for HER2-positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non-inferiority, phase III trial in Japan (JBCRG-M06/EMERALD). [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. [2021]

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

New directions with capecitabine combinations in advanced breast cancer. [2015]