IPH5201 + Durvalumab + Chemotherapy for Lung Cancer

(MATISSE Trial)

Recruiting at 38 trial locations

Overseen By Innate Pharma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Innate Pharma

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: EGFR mutations, ALK translocations, Autoimmune disorders, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

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

Compensation: Varies

Number of Visits: 1

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a combination of treatments—IPH5201, an experimental treatment, and durvalumab, an immunotherapy drug—along with standard chemotherapy to assess safety and effectiveness for certain lung cancer types. It targets patients with early-stage non-small cell lung cancer (NSCLC) that can be surgically removed. Eligible participants should have newly diagnosed, resectable NSCLC and be preparing for specific surgeries, such as lobectomy. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take any other chemotherapy, investigational drugs, or immunosuppressive medications during the study.

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

Research has shown that the combination of IPH5201 and durvalumab was generally well-tolerated in earlier studies. IPH5201, whether used alone or with durvalumab, proved safe at effective doses. Participants in those studies experienced few serious side effects, and any minor issues were manageable.

Durvalumab is already approved for treating certain cancers, indicating extensive study and safety when used correctly.

Overall, this combination of treatments has not raised any major safety concerns. This should reassure potential participants about the treatment's safety in this new study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of IPH5201 and durvalumab with standard chemotherapy for lung cancer because it targets the CD39 pathway, which is different from most current treatments. While standard options like chemotherapy and immune checkpoint inhibitors focus on directly attacking cancer cells or boosting the immune system, IPH5201 works by inhibiting CD39, an enzyme that can suppress immune responses in the tumor environment. This unique approach has the potential to enhance the effectiveness of the immune system’s attack on cancer cells, offering hope for improved outcomes in lung cancer treatment.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that combining IPH5201 with durvalumab and standard chemotherapy, as studied in this trial, might improve treatment for early-stage non-small cell lung cancer (NSCLC). IPH5201 blocks CD39, a protein that can weaken the immune system's ability to fight cancer. Studies suggest that targeting this protein may enhance the effectiveness of durvalumab, an existing cancer treatment. Durvalumab has already proven effective in treating lung cancer, but adding IPH5201 could lead to better patient outcomes. Early trials demonstrated that this combination is safe and may help the immune system fight cancer cells more effectively. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with early-stage (II to IIIA) non-small cell lung cancer that can be surgically removed. They must have proper organ function, not be pregnant, and agree to use contraception. Excluded are those with small-cell lung cancer, certain genetic mutations, autoimmune diseases, another primary malignancy, or severe cardiovascular disease.

Inclusion Criteria

You are expected to live for at least 12 more weeks.

I am using birth control during the study period.

My organs and bone marrow are working well.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I have previously been given durvalumab or IPH5201 in this study.

Participation in another clinical study with an investigational product administered within 30 days prior to enrolment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant therapy with IPH5201 and durvalumab in addition to standard chemotherapy before surgery

16 weeks

Multiple visits for treatment administration

Surgery

Participants undergo surgical resection

1 week

1 visit for surgery

Adjuvant Treatment

Participants receive adjuvant treatment with IPH5201 and durvalumab post-surgery

Up to 4 months

Multiple visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• IPH5201
• Standard Chemotherapy

Trial Overview The study tests the combination of IPH5201 and durvalumab with standard chemotherapy before surgery (neoadjuvant therapy), followed by the same drugs after surgery (adjuvant therapy). It aims to evaluate safety and effectiveness in untreated NSCLC patients eligible for tumor removal.

How Is the Trial Designed?

Group I: IPH5201 + durvalumab + standard chemotherapy Experimental Treatment 1 Intervention

Patients will receive Neoadjuvant therapy with IPH5201 and durvalumab in addition to standard chemotherapy. Following surgery, patients will receive adjuvant treatment with IPH5201 and durvalumab.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Innate Pharma

Lead Sponsor

Trials

29

Recruited

3,100+

Published Research Related to This Trial

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

In the phase 3 POSEIDON study involving 1013 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC), the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Patients receiving the combination treatment also experienced a longer time to deterioration in quality of life and various symptoms, indicating better overall health status compared to those on chemotherapy, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). Garon, EB., Cho, BC., Luft, A., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to provide a survival benefit as a maintenance therapy for patients with unresectable stage III non-small-cell lung cancer (NSCLC) after chemoradiotherapy, and it is approved by major regulatory agencies.

While durvalumab can cause immune-mediated adverse events, its safety profile is comparable to other PD-1/PD-L1 inhibitors, with most side effects being manageable and mild, although combination therapies may increase the risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of durvalumab for the treatment of non-small-cell lung cancer. Shibata, Y., Murakami, S.[2022]

In the phase III PACIFIC trial, durvalumab treatment led to a low incidence of immune-mediated adverse events (imAEs), with any-grade immune-mediated pneumonitis occurring in 9.4% of patients and grade 3/4 imAEs in only 3.4%.

Despite the occurrence of imAEs being more common with durvalumab compared to placebo, these events were generally manageable with treatments like corticosteroids, indicating that the benefits of the PACIFIC regimen outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Naidoo, J., Vansteenkiste, JF., Faivre-Finn, C., et al.[2022]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

Immune checkpoint inhibitors (ICIs), particularly durvalumab, have significantly improved treatment outcomes for patients with advanced non-small cell lung cancer (NSCLC), establishing them as the standard of care either alone or with chemotherapy.

Durvalumab is specifically approved as a consolidation treatment after chemo-radiotherapy for stage III NSCLC, highlighting its role in enhancing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. Gullapalli, S., Remon, J., Hendriks, LEL., et al.[2020]

In the phase III CASPIAN trial involving previously untreated adults with extensive-stage small cell lung cancer (ES-SCLC), the addition of durvalumab to chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Durvalumab combined with etoposide and either carboplatin or cisplatin demonstrated a manageable safety profile, making it a valuable first-line treatment option and an accepted standard of care for patients with ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Extensive-Stage SCLC. Al-Salama, ZT.[2022]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In the phase III CASPIAN study, the combination of durvalumab with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer compared to etoposide plus platinum alone.

Patient-reported outcomes showed that the addition of durvalumab not only maintained quality of life but also delayed the worsening of key symptoms like appetite loss, cough, and fatigue, indicating a beneficial impact on patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Goldman, JW., Garassino, MC., Chen, Y., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12451260/

IPH5201, an Anti-CD39 mAb, as Monotherapy or in ... This report provides the first-in-human clinical safety and efficacy data for IPH5201, an anti-CD39 mAb, administered as monotherapy or in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05742607

IPH5201 and Durvalumab in Patients With Resectable Non ... The study is intended to assess the safety and efficacy of neoadjuvant combination of IPH5201 and durvalumab in addition to standard chemotherapy and ...

3. innate-pharma.com innate-pharma.com/sites/default/files/Poster%20ESMOIO%202022%20IPH52%20preclinical.pdf

Combination of IPH5201, a blocking antibody targeting the ... Targeting the Ado pathway has recently been reported to improve Durvalumab efficacy in early-stage Non-Small Cell Lung Cancer (NSCLC) patients, through the use ...

4. withpower.com withpower.com/trial/phase-2-lung-neoplasms-1-2023-69114

IPH5201 + Durvalumab + Chemotherapy for Lung Cancer Durvalumab, a part of this treatment, has been shown to have a manageable safety profile in lung cancer patients, but it can cause immune-related side effects ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40899626/

IPH5201, an anti-CD39 monoclonal antibody, as ... Results: Overall, 38 patients received IPH5201 monotherapy and 19 received IPH5201 + durvalumab, with median duration of follow-up 7.6 months ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05742607

IPH5201 and Durvalumab in Patients With Resectable Non ... The study is intended to assess the safety and efficacy of neoadjuvant combination of IPH5201 and durvalumab in addition to standard chemotherapy and ...

7. innate-pharma.com innate-pharma.com/media/all-press-releases/first-patient-dosed-phase-2-matisse-trial-iph5201-early-stage-lung-cancer

First patient dosed in Phase 2 MATISSE trial of IPH5201 in ... The study aims to assess the potential of combining our IPH5201 drug candidate with durvalumab as neoadjuvant treatment with chemotherapy and ...

8. esmoiotech.org esmoiotech.org/article/S2590-0188(22)00231-3/pdf

188P IPH5201 as monotherapy or in combination with ... IPH5201 is a blocking anti-CD39 monoclonal antibody (mAb) that may promote antitumor im- munity by accumulating immunostimulatory ATP released by necrotic cells ...

9. researchgate.net researchgate.net/publication/395237452_IPH5201_an_Anti-CD39_mAb_as_Monotherapy_or_in_Combination_with_Durvalumab_in_Advanced_Solid_Tumors

(PDF) IPH5201, an Anti-CD39 mAb, as Monotherapy or in ... Conclusions IPH5201 as monotherapy, or in combination with durvalumab, was well tolerated at pharmacologically active doses that induced ...