NKTR-255 + Durvalumab for Lung Cancer

Overseen By Steven H. Lin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-PD-1, Anti-PD-L1, IL-2, IL-5

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 year

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing NKTR-255 and durvalumab in patients with advanced lung cancer who have had previous treatment. The goal is to boost their immune system to better fight the cancer. Durvalumab has shown survival benefits for patients after their initial treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Durvalumab for lung cancer?

Research shows that Durvalumab significantly improves survival in patients with stage III non-small-cell lung cancer (NSCLC) who have not progressed after chemoradiotherapy. It has been shown to prolong both overall survival and progression-free survival, making it an effective treatment option for this condition. ^{1 2 3 4 5}

Is the combination of NKTR-255 and Durvalumab safe for humans?

Durvalumab, also known as MEDI4736 or Imfinzi, has been shown to have a manageable safety profile in treating various cancers, including non-small-cell lung cancer. It is generally well-tolerated, but some patients may experience side effects like reduced appetite and diarrhea. The combination of durvalumab with other drugs, such as tremelimumab, has shown increased adverse events, so careful monitoring is important. ^{4 5 6 7 8}

What makes the drug Durvalumab unique for lung cancer treatment?

Durvalumab is unique because it is the only drug approved as a consolidation treatment after chemoradiotherapy for stage III non-small cell lung cancer (NSCLC), working by blocking PD-L1, a protein that helps cancer cells evade the immune system. ^{2 4 5 9 10}

Research Team

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with non-small cell lung cancer (NSCLC) who intend to undergo definitive cancer treatment, have an ECOG performance status of 0-2, and proper liver and kidney function. Participants must not have other current malignancies except certain skin cancers or a history of another cancer cured over five years ago without recurrence.

Inclusion Criteria

I have been diagnosed with non-small cell lung cancer.

My liver and kidney tests are within normal limits.

My treatment is aimed at curing my cancer.

Exclusion Criteria

I do not have any serious illnesses or infections that need treatment.

Other condition or prior therapy that, in the opinion of the Investigator, compromises the subject's welfare or may confound study results

Pregnancy: a female subject defined as a WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Participants undergo chemoradiotherapy (CRT) as part of the standard treatment for NSCLC

6-8 weeks

Treatment

Participants receive NKTR-255 and durvalumab after completing CRT. The first dose of NKTR-255 is given within 72 hours after CRT, followed by a second dose at 3 weeks, and then every 4 weeks for up to 1 year.

1 year

1 visit every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Durvalumab
• NKTR-255

Trial Overview The study tests the effects of NKTR-255 combined with durvalumab on NSCLC after chemoradiotherapy (CRT). NKTR-255 is investigational, while durvalumab is standard care. The goal is to see how well these drugs work together following CRT in advanced lung cancer cases.

Participant Groups

Group I: NKTR-255 combination (Durvalumab) Experimental Treatment 2 Interventions

Participants will receive vein over about 30 minutes. Participants receive the first dose within 72 hours (3 days) after you complete CRT and the second dose at 3 weeks after you complete CRT. Then, you will receive NKTR-255 one (1) time every 4 weeks after that for up to 1 year. Durvalumab Participants will receive durvalumab by vein over about 30 minutes. You will receive the first dose at 3 weeks after you complete CRT therapy. Then, you will receive durvalumab one (1) time every 4 weeks after that for up to 1 year

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Nektar Therapeutics

Industry Sponsor

Trials

59

Recruited

9,900+

Howard W. Robin

Nektar Therapeutics

Chief Executive Officer since 2007

B.S. in Accounting and Finance from Fairleigh Dickinson University

Dr. Dimitry Nuyten

Nektar Therapeutics

Chief Medical Officer since 2022

MD

Findings from Research

In a phase 3 trial involving 713 patients with stage III unresectable non-small-cell lung cancer, durvalumab significantly improved overall survival compared to placebo, with a 24-month survival rate of 66.3% versus 55.6%.

Durvalumab also prolonged progression-free survival, with a median duration of 17.2 months compared to 5.6 months for placebo, and no new safety concerns were identified, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. Antonia, SJ., Villegas, A., Daniel, D., et al.[2022]

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 PACIFIC trial, durvalumab significantly improved overall survival (OS) and progression-free survival (PFS) in patients with unresectable stage III non-small-cell lung cancer after chemoradiotherapy, with a 5-year OS rate of 42.9% compared to 33.4% for placebo.

The updated analyses, with a median follow-up of 34.2 months, showed that durvalumab continues to provide durable benefits, establishing a new standard of care for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. Spigel, DR., Faivre-Finn, C., Gray, JE., et al.[2022]

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]

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]

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]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

The PACIFIC study demonstrated that durvalumab, an immune checkpoint inhibitor, significantly improves both progression-free and overall survival in patients with unresectable stage III non-small cell lung cancer (NSCLC) when used as consolidation therapy after concurrent chemotherapy and radiation, marking a major advancement in treatment for this patient group.

Durvalumab has a favorable safety profile and has been approved as a standard treatment in multiple countries, addressing the urgent need for effective therapies in a population that has seen no improvement in outcomes for over a decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives. Inoue, H., Okamoto, I.[2020]

In a study of 924 patients with unresectable stage III non-small cell lung cancer treated with durvalumab, race did not significantly affect treatment patterns such as initiation delays, interruptions, or discontinuations.

Black patients experienced fewer immune-related adverse events and pneumonitis compared to White patients, suggesting potential differences in safety profiles between racial groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration. Moore, AM., Nooruddin, Z., Reveles, KR., 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]

References

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

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. [2022]

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

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

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

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [2022]

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

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

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

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

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

Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration. [2023]

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

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