IPH5201 + Durvalumab + Chemotherapy for Lung Cancer

Recruiting at 32 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

Trial Summary

What is the purpose of this trial?

The study is intended to assess the safety and efficacy of neoadjuvant combination of IPH5201 and durvalumab in addition to standard chemotherapy and adjuvant combination of IPH5201 and durvalumab in untreated patients with resectable, early-stage (stage II to IIIA) non-small cell lung cancer (NSCLC).

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.

What data supports the effectiveness of the drug combination IPH5201, Durvalumab, and chemotherapy for lung cancer?

Research shows that Durvalumab, when used alone or with chemotherapy, improves survival in non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). It is particularly effective as a maintenance therapy after chemoradiotherapy in NSCLC and has shown significant survival benefits in combination with chemotherapy in SCLC. ^{1 2 3 4 5}

Is the combination of IPH5201, Durvalumab, and chemotherapy generally safe for humans?

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 like pneumonitis (lung inflammation), which can be serious. About 25% of patients in a study experienced immune-related side effects, with 3.4% having severe reactions. ^{1 2 6 7 8}

What makes the drug combination of IPH5201, Durvalumab, and chemotherapy unique for lung cancer?

This treatment combines Durvalumab, an immune checkpoint inhibitor that blocks PD-L1 to help the immune system attack cancer cells, with IPH5201, a novel antibody targeting CD39, and standard chemotherapy. This combination aims to enhance the immune response against lung cancer, potentially offering a new approach for patients who may not respond well to existing treatments. ^{1 2 4 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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 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]

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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

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

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. [2020]

3. Ireland 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). [2023]

4. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of durvalumab for the treatment of non-small-cell lung cancer. [2022]

5. Ireland 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. [2021]

6. Ireland 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. [2022]

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

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

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

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Extensive-Stage SCLC. [2022]

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

Durvalumab for the treatment of non-small cell lung cancer. [2019]