Chemo-Immunotherapy for Breast Cancer

(AIPAC-003 Trial)

Recruiting at 22 trial locations

Overseen By Chief Medical Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Immutep S.A.S.

Must be taking: Paclitaxel

Must not be taking: PD-1/PD-L1 therapy

Disqualifiers: Prior chemotherapy, ET therapy, others

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

Compensation: Varies

Number of Visits: Unknown

849 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare the safety and efficacy of eftilagimod alpha (efti) in combination with paclitaxel standard of care chemotherapy in participants with metastatic breast cancer. The main questions it aims to answer are: * What is the optimal biological dose (OBD) of efti in combination with weekly paclitaxel chemotherapy? * Can efti combined with weekly paclitaxel chemotherapy prolong overall survival in participants with metastatic breast cancer if compared to weekly paclitaxel chemotherapy alone? In the first component of the trial (phase 2, lead-in) researchers will compare two groups (different dose levels of efti in combination with standard chemotherapy) to see if the treatment is safe and well tolerated and evaluate which is the optimal biological dose. In the second component of the trial (phase 3) researchers will assess if the treatment of metastatic breast cancer with the optimal biological dose of efti in combination with paclitaxel is superior compared to chemotherapy alone (placebo-controlled). The treatment concept of each trial component consists of a chemo-immunotherapy phase followed by an immunotherapy phase. In the first phase participants will be treated with efti plus paclitaxel chemotherapy or placebo plus paclitaxel chemotherapy. After completion of the chemotherapy per standard of care, participants will be treated with the study agent alone.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants should not have had prior chemotherapy for metastatic breast cancer, which might imply some restrictions. It's best to discuss your current medications with the trial coordinators.

What data supports the effectiveness of the drug combination including Eftilagimod Alpha and Paclitaxel for breast cancer?

Research shows that Paclitaxel, a component of the treatment, is effective in improving survival rates and reducing tumor recurrence in breast cancer patients. It has shown significant antitumor activity, especially in combination with other drugs, and is effective even in cases resistant to other treatments. ^{1 2 3 4 5}

Is the chemo-immunotherapy treatment safe for humans?

Paclitaxel, a component of the treatment, has been studied extensively and is generally safe for humans, though it can cause side effects like low white blood cell counts, nerve damage, and allergic reactions. These side effects are often managed with premedication and careful dosing. ^{6 7 8 9 10}

What makes the chemo-immunotherapy treatment with Eftilagimod Alpha and Paclitaxel unique for breast cancer?

This treatment is unique because it combines Eftilagimod Alpha, an immunotherapy agent that helps the immune system fight cancer, with Paclitaxel, a chemotherapy drug that disrupts cancer cell division. This combination aims to enhance the overall effectiveness against breast cancer by using two different mechanisms of action. ^{1 5 7 11 12}

Eligibility Criteria

This trial is for individuals with metastatic breast cancer who are set to receive paclitaxel chemotherapy. It's open to those with triple-negative breast cancer not getting PD-1/PD-L1 therapy, or hormone receptor-positive patients after at least one endocrine therapy. Participants should be in good physical condition (ECOG 0-1) and expected to live more than three months.

Inclusion Criteria

I have triple-negative breast cancer and am to receive paclitaxel without PD 1/PD-L1 therapy for metastatic disease.

My HR+ breast cancer has worsened after endocrine therapy, and I need chemotherapy.

My breast cancer is either hormone receptor positive or negative, and HER2 negative.

Exclusion Criteria

My cancer returned less than a year after my last chemotherapy.

My breast cancer responds to hormone therapy and I am eligible for such treatment.

I have HR+ metastatic breast cancer and received less than one line of hormone therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Optimization Lead-in (Phase 2)

Evaluation of safety and tolerability of different dose levels of efti combined with paclitaxel to define the optimal biological dose

24 months

Chemo-Immunotherapy Phase

Participants receive efti plus paclitaxel chemotherapy or placebo plus paclitaxel chemotherapy

6 cycles of 4 weeks each

Immunotherapy Phase

Participants are treated with the study agent alone following chemotherapy

13 cycles (approx. 12 months)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Eftilagimod Alpha
• Paclitaxel
• Placebo

Trial Overview Researchers are testing eftilagimod alpha (efti), an immunotherapy drug, combined with standard paclitaxel chemotherapy against placebo plus chemotherapy. They aim to find the best dose of efti and see if it improves survival rates compared to chemotherapy alone in two phases: chemo-immunotherapy followed by immunotherapy.

Participant Groups

Group I: open label lead-in (phase 2): eftilagimod alpha 90mg + paclitaxel Experimental Treatment 2 Interventions

eftilagimod alpha 90mg s.c. + 80mg/m\^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned.

Group II: open label lead-in (phase 2): eftilagimod alpha 30mg + paclitaxel Experimental Treatment 2 Interventions

eftilagimod alpha 30mg s.c. + 80mg/m\^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned.

Group III: Phase 3: eftilagimod alpha + paclitaxel Experimental Treatment 2 Interventions

eftilagimod alpha s.c. (OBD) + 80mg/m\^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned.

Group IV: Phase 3: placebo + paclitaxel Placebo Group 2 Interventions

placebo s.c. + 80mg/m\^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned.

Who Is Running the Clinical Trial?

Immutep S.A.S.

Lead Sponsor

Trials

15

Recruited

2,600+

Findings from Research

In two large randomized trials, adding intravenous paclitaxel to standard doxorubicin-cyclophosphamide (AC) therapy significantly improved disease-free survival at 5 years for women with early breast cancer, with one trial also showing improved overall survival.

While paclitaxel demonstrated efficacy in neoadjuvant therapy by increasing response rates and eligibility for breast-conserving surgery, it was associated with notable grade 3-4 adverse events, primarily hematological issues like neutropenia and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel: as adjuvant or neoadjuvant therapy in early breast cancer. Simpson, D., Plosker, GL.[2018]

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

In a phase II study involving 25 patients with metastatic breast cancer, paclitaxel demonstrated significant efficacy, with 14 patients achieving a major response and a median survival time of 20 months.

Paclitaxel remains effective even in patients who have undergone multiple prior chemotherapy regimens, including those resistant to anthracyclines, although combination therapies can lead to serious side effects like neutropenic fever and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. Hortobagyi, GN., Holmes, FA., Ibrahim, N., et al.[2015]

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]

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

Paclitaxel (TAXOL) is an effective chemotherapy drug that works by disrupting microtubule function, showing significant activity against advanced ovarian, breast, and non-small cell lung cancers, among others.

With proper premedication, the incidence of hypersensitivity reactions to paclitaxel has been reduced to 3%, although neutropenia remains a major dose-limiting side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. Hájek, R.[2015]

Taxol, when administered intravenously, has a well-established safety profile based on data from 655 patients, with myelosuppression, particularly neutropenia, identified as the main dose-limiting toxicity, which was less severe with a 3-hour infusion schedule.

Severe hypersensitivity reactions were effectively managed with a premedication regimen, and while mild to moderate peripheral neuropathy was observed, it rarely led to treatment discontinuation, indicating a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Taxol safety. Onetto, N., Canetta, R., Winograd, B., et al.[2015]

Paclitaxel, a drug used to treat various cancers, has traditionally been known to cause cell death by inducing mitotic arrest, but new evidence suggests that it may actually lead to multipolar cell divisions due to low intratumoral concentrations.

This new understanding of paclitaxel's mechanism of action could help develop a biomarker to identify the approximately 50% of patients who are likely to benefit from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Taxol/paclitaxel kills cancer cells. Weaver, BA.[2022]

In a study of 33 patients with progressive or recurrent non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, Abraxane showed a partial response rate of 33.3%, with better outcomes in patients with squamous cell carcinoma (41.7% response) compared to those with adenocarcinoma (21.1%).

The treatment demonstrated a disease control rate of 75.8% and a median progression-free survival of five months, with manageable side effects, indicating that Abraxane is a potentially effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. Yuan, DM., Lv, YL., Yao, YW., et al.[2019]

Paclitaxel (Taxol) is a significant new chemotherapy drug for breast cancer, showing promise in both single-agent and combination treatments.

Ongoing research at Memorial Sloan-Kettering Cancer Center aims to optimize the use of paclitaxel in various treatment settings, including metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. Seidman, AD., Hudis, CA., Fennelly, D., et al.[2015]

References

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

Paclitaxel: as adjuvant or neoadjuvant therapy in early breast cancer. [2018]

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

Management of breast cancer: status and future trends. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

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

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. [2015]

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

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

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

Paclitaxel (taxol). [2019]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. [2015]

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

Overview of Taxol safety. [2015]

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

How Taxol/paclitaxel kills cancer cells. [2022]

10. Singapore pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. [2019]

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

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. [2015]

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

Phase I study of escalating doses of mitoxantrone and paclitaxel with granulocyte-macrophage colony stimulating factor support. [2015]