C-TIL051 + Anti-PD1 Therapy for Lung Cancer

Recruiting at 3 trial locations

Overseen By Nurat Quadri, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbelZeta, Inc.

Must be taking: Anti-PD1

Must not be taking: Immunosuppressives, Live vaccines

Disqualifiers: CNS metastases, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new treatment for non-small cell lung cancer that resists standard treatments. It combines a specially developed therapy using a person's own tumor cells (C-TIL051) with other immune-boosting drugs, including Anti-PD1 therapy, to evaluate its effect on the cancer. People with stage IV or recurring non-small cell lung cancer, who have surgically removable tumors and have not received certain immune therapies, might be suitable candidates. The trial involves several steps, including receiving the new treatment and regular check-ups to monitor progress. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does exclude those who have used immunosuppressive medications within 14 days before tumor harvest. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

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

Research shows that C-TIL051, a new lung cancer treatment, is being tested for safety and tolerability. This treatment uses a person's own immune cells, grown in a lab, to fight cancer. As this is an early-stage study, unknown risks may exist.

Studies of similar treatments have shown that side effects can occur, but they are often manageable. These might include fever, chills, or tiredness. However, the specific effects of C-TIL051 remain uncertain due to its novelty.

The study also includes NKTR-255 and pembrolizumab. NKTR-255 aims to boost the immune system. Pembrolizumab, already used for other cancers, has some known safety information. Common side effects include tiredness, skin rash, or nausea.

Overall, this study provides an early look at how these treatments work together. Safety remains a primary focus, and more data will clarify any risks involved. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about C-TIL051 because it combines a novel approach with existing immunotherapy to tackle lung cancer. Unlike standard treatments that typically focus on chemotherapy or radiation, this therapy uses a combination of C-TIL051 with IL-15 (NKTR-255) and pembrolizumab to enhance the body's immune response specifically against cancer cells. The unique aspect of C-TIL051 is its potential to boost immune cell activity, offering a targeted approach that might lead to more effective and sustained cancer control. This method could represent a significant advancement over current options by potentially reducing side effects and improving treatment outcomes.

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

Research shows that a type of immune cell treatment called tumor infiltrating lymphocytes (TILs), specifically C-TIL051, has potential in treating non-small cell lung cancer (NSCLC). In earlier studies, about 21% of patients with NSCLC responded to TIL therapy, with some remaining cancer-free for a long time. This trial will administer a combination of C-TIL051 with NKTR-255, which helps immune cells survive and remember cancer, and Pembrolizumab, a therapy that blocks cancer's defenses. This combination is designed to boost the immune system's fight against cancer. By increasing the number and staying power of TILs, this approach aims to enhance the body's ability to combat tumors. These findings suggest possible benefits for patients with hard-to-treat NSCLC. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with stage IV or recurrent non-small cell lung cancer (NSCLC) who haven't responded to standard treatments. They must have a heart function test showing normal results, adequate organ and marrow function, and no serious infections like HIV or hepatitis. Pregnant women, those unwilling to use contraception, and patients with certain lung conditions or recent immunosuppressive drug use are excluded.

Inclusion Criteria

Your recent lung function tests show that your lungs are working well.

My lung cancer is confirmed to be stage IV or recurrent NSCLC with adenocarcinoma or squamous cell type.

Your heart tests from the past 6 months show that your heart is working well and there are no signs of heart problems.

Exclusion Criteria

Any condition that may interfere with evaluation of study treatment, safety or study results

I am allergic to certain cancer drugs or their ingredients.

I am willing to use contraception during and 6 months after the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tumor Sample Collection

Participants provide a tumor sample prior to the start of any treatment which will be used to make the C-TIL051

1 week

Standard of Care Treatment

Participants receive standard of care treatment until their lung cancer no longer responds

Variable

Lymphodepletion Chemotherapy

Participants receive chemotherapy (called lymphodepletion) for 3 days followed by 2 days of rest

1 week

C-TIL051 Infusion and NKTR-255 Administration

C-TIL051 is infused on day 0 followed by NKTR-255 (IL-15) about 12 to 24 hours later

1 day

Pembrolizumab Treatment

Pembrolizumab is administered every 3 weeks for up to 2 years

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• C-TIL051

Trial Overview The study tests C-TIL051 combined with NKTR-255 and anti-PD1 therapy in NSCLC patients whose cancer hasn't improved with standard care. It involves taking a tumor sample to create C-TIL051, chemotherapy preparation, followed by infusions of C-TIL051 and NKTR-255, then regular Pembrolizumab injections for up to two years.

How Is the Trial Designed?

Group I: C-TIL051 Experimental Treatment 1 Intervention

C-TIL051 plus IL-15 (NKTR-255) and Pembrolizumab

Who Is Running the Clinical Trial?

AbelZeta, Inc.

Lead Sponsor

Trials

1

Recruited

20+

AbelZeta Inc.

Lead Sponsor

Cellular Biomedicine Group, Inc.

Lead Sponsor

Trials

3

Recruited

270+

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

In a study of 74 patients with stage III non-small cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy, high density of CD8+ tumor-infiltrating lymphocytes (TILs) was found to be a significant predictor of better progression-free survival (PFS) and overall survival (OS), while PD-L1 expression did not correlate with these outcomes.

Patients with low PD-L1 expression and high CD8+ TIL density had the best survival rates, suggesting that assessing both PD-L1 and CD8+ TILs could serve as a valuable predictive biomarker for treatment efficacy in stage III NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy. Tokito, T., Azuma, K., Kawahara, A., et al.[2022]

In a study of 378 non-small cell lung cancer (NSCLC) patients, high levels of CD8+PD-L1+ tumor-infiltrating lymphocytes (TILs) were associated with a worse prognosis in patients not receiving immunotherapy, indicating an immunosuppressive tumor microenvironment.

However, in patients undergoing anti-PD-1 treatment, higher levels of CD8+PD-L1+ TILs correlated with better responses to therapy, suggesting that PD-1 pathway blockade can alleviate immunosuppression and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Massive PD-L1 and CD8 double positive TILs characterize an immunosuppressive microenvironment with high mutational burden in lung cancer. Zhang, L., Chen, Y., Wang, H., et al.[2022]

A total of 686 clinical trials are currently investigating anti-PD-(L)1 agents for intrathoracic tumors, with a significant focus on non-small cell lung cancer (NSCLC), indicating a robust interest in this area of immunotherapy.

The majority (81%) of these trials are exploring combination treatments, often pairing PD-(L)1 blockade with chemotherapy or other immunotherapies, highlighting a trend towards more comprehensive treatment strategies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors. Kareff, SA., Samtani, S., Burotto, M., et al.[2022]

In a review of 23 randomized controlled trials involving 15,797 patients, PD-1 inhibitors significantly improved overall survival (OS) by an average of 4.80 months compared to standard care, while PD-L1 inhibitors improved OS by 2.59 months.

PD-1 inhibitors were found to provide greater OS benefits than PD-L1 inhibitors, suggesting that PD-1 inhibitors may be the preferred choice for treating advanced non-small-cell lung cancer (NSCLC), especially in patients with varying PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relative and absolute benefit of programmed death receptor-1 vs programmed death ligand 1 therapy in advanced non-small-cell lung cancer: A systematic review and meta-analysis. Yi, K., Zhu, Q., Kuang, YK., et al.[2021]

PD-L1 is a critical factor in regulating T-cell activation and immune response, particularly in non-small cell lung cancer (NSCLC), where higher PD-L1 expression is associated with better responses to PD-1 inhibitors like pembrolizumab.

The study emphasizes the importance of assessing PD-L1 expression levels across different lung cancer subtypes, as this can significantly influence treatment decisions and the effectiveness of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies? Ullah, A., Pulliam, S., Karki, NR., et al.[2022]

Inhibition of the PD1/PDL1 pathway shows promise in treating non-small cell lung cancer (NSCLC), with anti-PD1 antibody nivolumab achieving objective responses in 13-18% of patients who had previously failed treatment, and anti-PDL1 antibodies showing similar responses of 6-22%.

While these therapies can restore immune response against tumors, they also carry risks of new adverse events, including autoimmune diseases, and further research is needed to clarify treatment duration and evaluation criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy in non-small cell lung cancer: inhibition of PD1/PDL1 pathway]. Guilleminault, L., Carmier, D., Heuzé-Vourc'h, N., et al.[2018]

Lung cancer cells express both membrane-bound PD-L1 and soluble PD-L1, which significantly inhibit the proliferation of T lymphocytes, suggesting a mechanism for immune evasion by tumors.

The study found that activated T lymphocytes showed high levels of PD-1 expression, and blocking PD-L1 with an antibody could partially restore T cell proliferation, indicating potential therapeutic strategies to enhance anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of soluble PD-L1 released by lung cancer cells in regulating the function of T lymphocytes]. Shi, MH., Xing, YF., Zhang, ZL., et al.[2021]

In a review of 22 clinical trials involving 2,231 patients with advanced non-small cell lung cancer, the incidence of all-grade pneumonitis was found to be 2.9% for patients receiving PD-1 and PD-L1 inhibitors, which is significantly higher than the incidence in those receiving standard chemotherapy (OR=2.35).

While pneumonitis and other immune-related adverse effects (IRAEs) can be severe, the overall incidence of treatment-related deaths was low at 0.7%, indicating that while these therapies can have serious side effects, they are generally rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of rare but severe immune related adverse effects in PD-1 and PD-L1 inhibitors in non-small cell lung cancer: a meta-analysis. Hu, YB., Zhang, Q., Li, HJ., et al.[2022]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

In a meta-analysis of 18 studies involving 5,649 patients with non-small cell lung cancer, first-line therapy using PD-1/PD-L1 inhibitors showed a significantly higher risk of treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) compared to subsequent therapies, indicating a need for careful monitoring in initial treatments.

Despite the higher incidence of adverse events in first-line therapy, the types of trAEs and irAEs were largely similar across different therapy lines, suggesting that while the severity may differ, the overall spectrum of side effects remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. Yang, Y., Pang, P., Xie, Z., et al.[2022]

In a study of 56 patients with advanced non-small-cell lung cancer (NSCLC) and concurrent autoimmune disease (AID) treated with PD-1 or PD-L1 inhibitors, 55% experienced an AID flare or immune-related adverse event (irAE), but most were manageable and did not lead to treatment discontinuation.

The overall response rate to PD-(L)1 therapy in this population was 22%, indicating that while there are risks, the treatment can still be effective for patients with NSCLC and AID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders. Leonardi, GC., Gainor, JF., Altan, M., et al.[2022]

In a study of 191 patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors, those who experienced immune-related adverse events (irAEs) had significantly better treatment outcomes, with an objective response rate of 42.0% compared to 25.8% in those without irAEs.

The presence of irAEs was associated with improved progression-free survival, suggesting that these adverse events may indicate a more effective immune response to the treatment, although they did not correlate with overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China. Chen, X., Nie, J., Dai, L., et al.[2022]

Citations

1. cancer.gov cancer.gov/clinicaltrials/NCI-2024-04398

C-TIL051 in Non-Small Cell Lung Cancer - NCI The purpose of this study is to: 1. Test the safety and ability for subjects to tolerate the TIL therapy 2. Measure to see how the NSCLC responds to the TIL ...

2. ir.nektar.com ir.nektar.com/news-releases/news-release-details/nektar-therapeutics-announces-new-clinical-study-collaboration

Nektar Therapeutics Announces New Clinical Study ... C-TIL051 is an autologous adoptive cell therapy being developed by CBMG that is comprised of a patient's ex vivo expanded lymphocytes using ...

3. cgtlive.com cgtlive.com/view/new-til-therapy-to-be-assessed-in-nsclc

New TIL Therapy to be Assessed in NSCLC The FDA has granted clearance of Cellular Biomedicine Group's investigational new drug application (IND) of CT-TIL051, a tumor infiltrating lymphocyte (TIL) ...

4. mskcc.org mskcc.org/news/til-therapy-for-non-small-cell-lung-cancer-new-immunotherapy-may-be-effective

TIL Therapy for Non-Small Cell Lung Cancer May Be ... “The fact that 21% of the non-small cell lung cancer patients responded to TIL therapy is significant. Some patients remained free of cancer ...

5. app.trialscreen.org app.trialscreen.org/trials/phase-1-metastatic-non-small-cell-lung-cancer-c-til051-trial-nct05676749

C-TIL051 in Non-Small Cell Lung Cancer The combination of C-TIL051, NKTR-255, and anti-PD1 therapy may improve the proliferation and persistence of the tumor-infiltrating lymphocytes (C-TIL051), ...

6. news.biobuzz.io news.biobuzz.io/2025/07/16/cellular-biomedicine-group-announces-fda-clearance-of-ind-application-for-novel-til-therapy-c-til051/

Cellular Biomedicine Group Announces FDA Clearance of IND ... FDA granted IND clearance for C-TIL051, CBMG's novel autologous TIL therapy, for the treatment of patients with Non-Small Cell Lung Cancer (NSCLC) ...