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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effects of a new drug, NKTR-255, combined with the standard immunotherapy drug durvalumab, on non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT). The research focuses on whether this combination can improve treatment outcomes for patients with locally advanced NSCLC. The trial seeks participants who have completed CRT and have been diagnosed with NSCLC without other active cancers. This trial may suit individuals who have finished their primary cancer treatment and are not dealing with other serious health issues. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

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

Research has shown that the combination of NKTR-255 and durvalumab is generally well-tolerated by people with non-small cell lung cancer (NSCLC). One study found that this treatment aids immune system recovery after chemoradiation, which uses drugs and radiation to kill cancer cells. Patients did not report major safety issues, indicating the treatment is manageable.

Additionally, durvalumab alone has a safety profile that is easy to manage for treating various cancers, including NSCLC. While some side effects may occur, they are usually not severe and can be handled easily. Overall, early findings suggest that the NKTR-255 and durvalumab combination is safe for most people in this setting. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lung cancer?

Researchers are excited about the NKTR-255 and Durvalumab combination because it offers a novel approach to treating lung cancer. Unlike standard treatments that often rely on chemotherapy or radiation, this combination enhances the immune system's ability to fight cancer. NKTR-255 works by stimulating natural killer cells and memory T cells, potentially leading to a more robust and sustained anti-cancer response. Durvalumab, an immune checkpoint inhibitor, helps the immune system detect and attack cancer cells. Together, they offer a promising new strategy that could improve outcomes for patients with lung cancer.

What evidence suggests that the NKTR-255 and durvalumab combination could be effective for lung cancer?

Research has shown that durvalumab can help patients with stage III non-small cell lung cancer (NSCLC) live longer after chemoradiotherapy (CRT). Studies found that durvalumab extended life for those whose cancer hadn't worsened post-CRT. In this trial, participants will receive a combination of durvalumab and NKTR-255. NKTR-255 has effectively reversed a drop in white blood cells caused by radiation. Specifically, one study showed that 9 out of 10 patients fully recovered their white blood cell counts within 8 weeks. This combination aids the immune system's recovery, which is crucial for fighting cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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]

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]

Citations

1. targetedonc.com targetedonc.com/view/nktr-255-shows-promise-for-reversing-radiation-induced-lymphopenia-in-nsclc

NKTR-255 Shows Promise for Reversing Radiation ... NKTR-255 in combination with durvalumab following chemoradiation was well-tolerated in patients with non–small cell lung cancer, with a safety

2. onclive.com onclive.com/view/dr-lin-on-the-safety-of-nktr-255-in-enhancing-immune-recovery-post-chemoradiation-in-locally-advanced-nsclc

Dr Lin on the Safety of NKTR-255 in Enhancing Immune ... Findings showed that in the first cohort of 10 patients, 9 experienced a complete recovery of lymphocyte counts by week 8, Lin explains. He ...

3. ir.nektar.com ir.nektar.com/news-releases/news-release-details/nektar-and-collaborators-present-late-breaking-results-phase-2

Nektar and Collaborators Present Late-breaking Results ... NKTR-255 effectively reversed radiation induced lymphopenia in patients with locally advanced NSCLC receiving consolidation therapy with durvalumab.

4. withpower.com withpower.com/trial/phase-2-lung-cancers-3-2023-2a5e2

NKTR-255 + 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 ...

5. imfinzihcp.com imfinzihcp.com/nsclc/stage-3/efficacy.html

IMFINZI® Efficacy for unresectable Stage III NSCLC Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. J Clin Oncol. 2022;40(12): ...

6. prnewswire.com prnewswire.com/news-releases/nektar-and-collaborators-present-late-breaking-results-from-phase-2-study-of-nktr-255-for-the-treatment-of-radiation-induced-lymphopenia-in-locally-advanced-non-small-cell-lung-cancer-patients-at-society-for-immunotherapy-of-cance-302298158.html

Nektar and Collaborators Present Late-breaking Results ... NKTR-255 effectively reversed radiation induced lymphopenia in patients with locally advanced NSCLC receiving consolidation therapy with durvalumab.