Chemo-Immunotherapy for Breast Cancer

(AIPAC-003 Trial)

Not currently recruiting at 26 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with metastatic breast cancer. It aims to determine if adding eftilagimod alpha (efti, an immunotherapy) to standard chemotherapy (paclitaxel) is safe and whether it extends patient survival compared to chemotherapy alone. The study consists of two parts: first, identifying the optimal dose of efti, and second, comparing the new treatment to standard care. It seeks participants with metastatic breast cancer that has spread and who have already tried at least one other line of endocrine therapy or require chemotherapy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that the combination of eftilagimod alpha (efti) and paclitaxel is generally safe for patients. In studies, this treatment demonstrated a manageable safety profile for individuals with certain types of breast cancer. Reports indicate that patients tolerated the combination well, with side effects similar to those expected from standard treatments.

Specifically, previous patients with HR+/HER2-low breast cancer experienced few serious side effects, suggesting that the treatment usually does not cause unexpected or severe problems.

Overall, the data so far suggests that the combination of efti and paclitaxel is safe and tolerable for people with metastatic breast cancer. These findings help ensure that participants in the clinical trial can feel more confident about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they combine a novel immunotherapy agent, eftilagimod alpha, with the chemotherapy drug paclitaxel. Unlike traditional treatments that mainly rely on chemotherapy or hormone therapy, eftilagimod alpha aims to boost the body's immune response against cancer cells. This approach may enhance the effectiveness of paclitaxel, potentially leading to improved outcomes. Moreover, the use of eftilagimod alpha in combination with paclitaxel could offer a more comprehensive attack on the cancer, targeting it from multiple angles, which is a significant advancement over current standard treatments.

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

Research shows that combining eftilagimod alpha (efti) with paclitaxel, a common chemotherapy drug, may help treat metastatic breast cancer. In this trial, some participants will receive this combination, which studies have found safe for patients. Although previous studies did not achieve all main goals, such as stopping cancer from worsening, they showed expected effects on the body and confirmed safety. Efti targets LAG-3, a protein that can weaken the immune system's response to cancer, helping the body fight the disease more effectively. These findings suggest the combination could improve overall survival for patients with metastatic breast cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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, 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]

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]

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 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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10831339/

Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in ...

The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer 2019;19 ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05747794

NCT05747794 | Study in Metastatic Breast Cancer Patients ...

Can efti combined with weekly paclitaxel chemotherapy prolong overall survival in participants with metastatic breast cancer if compared to weekly paclitaxel ...

3.

onclive.com

onclive.com/view/eftilagimod-alpha-plus-chemotherapy-lead-in-proves-safe-in-hr-her2-low-breast-cancer

Eftilagimod Alpha Plus Chemotherapy Lead-In Proves ...

Eftilagimod alpha in combination with chemotherapy displayed a manageable safety profile in HR+/HER2-low breast cancer.

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.1050

Combination of paclitaxel and a LAG-3 fusion protein ...

Combination of paclitaxel and a LAG-3 fusion protein (eftilagimod alpha), as a first-line chemoimmunotherapy in patients with metastatic breast ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37939105/

Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, ...

Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile ...

6.

immutep.com

immutep.com/immutep-presents-data-from-safety-lead-in-phase-of-aipac-003-at-esmo-breast-2024/

Immutep Presents Data from Safety Lead-in Phase of ...

... paclitaxel continue to be safe and well tolerated in these metastatic breast cancer patients. It is also positive at this early stage to see ...