Novel Drug Regimens for Lung Cancer

No longer recruiting at 81 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Docetaxel, Immunosuppressants, others

Disqualifiers: Autoimmune disease, CNS metastases, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new drug combinations to treat advanced non-small cell lung cancer (NSCLC) that has returned or resisted previous treatments. Researchers compare these new drug regimens to standard care to determine which is more effective. The trial consists of two parts: one gathers safety data, and the other directly compares new treatments with standard care. It suits those who have experienced disease progression after up to two lines of treatments for advanced NSCLC. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on medications that strongly affect certain liver enzymes (CYP3A4). It's best to discuss your current medications with the study team.

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

Research shows that the treatment combinations in this trial have yielded different safety results in other studies.

For the group receiving dostarlimab and GSK4428859A/EOS884448 (belrestotug), previous studies suggest a manageable safety profile. Side effects were reported but generally remained manageable. The development of belrestotug stopped due to mixed effectiveness results, not safety issues.

The group receiving dostarlimab, GSK4428859A/EOS884448, and GSK6097608 has also been studied. These studies showed promising response rates, and while safety was closely monitored, no major safety problems were reported.

For those in the feladilimab and docetaxel group, past research indicates that this combination is usually well-tolerated. Common side effects in similar studies included fatigue and nausea, but these were often manageable with standard care.

Lastly, the combination of feladilimab and ipilimumab is being explored for its potential to improve treatment outcomes. While specific safety data for these combinations are limited, the individual drugs have been used in cancer treatments before, suggesting a known safety profile.

Overall, while some known side effects exist, previous research suggests that the treatment regimens have a safety profile considered manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they target the disease through innovative mechanisms. Dostarlimab and GSK4428859A/EOS884448, for instance, are promising due to their action as immune checkpoint inhibitors, which help the immune system recognize and attack cancer cells more effectively. Feladilimab, combined with docetaxel, offers a novel approach by potentially enhancing the immune response alongside chemotherapy. Additionally, the inclusion of GSK6097608 in some regimens adds another layer of immune modulation, potentially improving outcomes for patients who do not respond well to current standard treatments like docetaxel alone. These combinations offer hope for more personalized and effective treatment options, aiming to improve survival rates and quality of life for lung cancer patients.

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

Research has shown that combining the drugs belrestotug and dostarlimab in patients with high levels of PD-L1 in their tumors results in a better response than dostarlimab alone. However, this combination did not slow the disease, leading to its development being stopped. In this trial, one group of participants will receive dostarlimab plus GSK4428859A/EOS884448/belrestotug, while another group will receive dostarlimab plus GSK4428859A/EOS884448/belrestotug plus GSK6097608.

In contrast, combining feladilimab with docetaxel, which another group of participants will receive, has improved patient survival, with an average survival time of 17.1 months. Meanwhile, the combination of feladilimab and ipilimumab, another treatment group in this trial, has been less successful, with only one patient showing partial improvement. These findings offer early insights into how these treatments might work for advanced lung cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer (NSCLC) who've had disease progression after standard treatments, including a platinum-based chemotherapy and PD(L)1 inhibitor therapy. They must have measurable disease, be in good physical condition (ECOG score of 0 or 1), and have proper organ function. Women participating should not be pregnant or breastfeeding and must follow contraceptive guidance if of childbearing potential.

Inclusion Criteria

I am a man and will use effective birth control during and for 4 months after treatment.

I had a positive response to previous PD(L)1 therapy but my cancer later progressed.

I can provide a tissue sample from my lung cancer, either new or from past tests.

Exclusion Criteria

Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator

I have not had major surgery within the last 28 days.

Toxicity from previous anticancer treatment that includes: Greater than or equal to (>=) Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation. History of myocarditis of any grade during a previous treatment with immunotherapy. Toxicity related to prior treatment that has not resolved to <= Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be <= Grade 2). History (current and past) of idiopathic pulmonary fibrosis, pneumonitis (for past- pneumonitis exclusion only if steroids were required for treatment), interstitial lung disease, or organizing pneumonia. Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions. Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Safety and PK/PD Evaluation

Open-label, optional, non-randomized part based on safety and pharmacokinetics/pharmacodynamics evaluation to generate additional data for novel regimens

Up to 2 years

Part 2: Randomized Treatment

Randomized, Phase II open-label part comparing the efficacy and safety of novel regimens with standard of care

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cobolimab
• Docetaxel
• Dostarlimab
• Feladilimab
• GSK4428859A/EOS884448
• GSK6097608
• Ipilimumab
• Niraparib

Trial Overview The trial is testing new treatments against the standard care for NSCLC that has relapsed or is refractory. It includes novel regimens either combined or as single agents. Part 1 assesses safety and pharmacokinetics, while Part 2 compares efficacy in a randomized phase II study.

How Is the Trial Designed?

Group I: Part 2: Participants receiving feladilimab and docetaxel Experimental Treatment 2 Interventions

Group II: Part 1: Participants receiving feladilimab and ipilimumab Experimental Treatment 2 Interventions

Group III: Part 1: Participants receiving dostarlimab plus GSK4428859A/EOS884448/belrestotug plus GSK6097608 Experimental Treatment 3 Interventions

Group IV: Part 1: Participants receiving dostarlimab plus GSK4428859A/EOS884448/belrestotug Experimental Treatment 2 Interventions

Group V: Part 2: Participants receiving SoC: docetaxel Active Control 1 Intervention

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

iTeos Belgium SA

Industry Sponsor

Trials

9

Recruited

950+

Published Research Related to This Trial

In a trial involving 385 patients with advanced non-small cell lung cancer (NSCLC), the combination of ganetespib and docetaxel showed an acceptable safety profile, with neutropenia being the most common severe side effect, affecting 41% of patients in the combination group.

Although the primary endpoints for progression-free survival (PFS) were not met in the overall population, significant benefits were observed in patients diagnosed with advanced adenocarcinoma more than 6 months prior, indicating potential for this subgroup to benefit from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1). Ramalingam, S., Goss, G., Rosell, R., et al.[2020]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing improved overall survival compared to best supportive care in both first- and second-line therapies, based on randomized trials.

When combined with gemcitabine, docetaxel resulted in similar efficacy to combinations with cisplatin but caused significantly fewer severe side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of docetaxel for advanced non-small cell lung cancer. Green, MR.[2018]

In a study of 118 stage IV non-small cell lung cancer patients, combining docetaxel with a PD-1/PD-L1 inhibitor significantly improved the disease control rate (89.9% vs. 73.5%) compared to the PD-1/PD-L1 inhibitor alone.

While the combination treatment did not show a significant difference in overall response rates or 1-year progression-free survival, it was associated with a higher incidence of bone marrow suppression, although most adverse reactions were mild and tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Analysis of Docetaxel Combined with PD-1/PD-L1 Inhibitor in Second-line Treatment of Advanced Non-small Cell Lung Cancer]. Chen, Q., Li, Y., Zhang, W., et al.[2022]

In a study of 829 patients with previously treated non-small-cell lung cancer, oral topotecan demonstrated noninferiority to intravenous docetaxel in terms of 1-year survival rates, with 25.1% for topotecan compared to 28.7% for docetaxel.

Both treatments had different safety profiles; docetaxel was associated with higher rates of severe neutropenia (60% vs. 50%), while topotecan led to more cases of severe anemia and thrombocytopenia (26% vs. 10% and 26% vs. 7%, respectively).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. Ramlau, R., Gervais, R., Krzakowski, M., et al.[2018]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing survival benefits in both first- and second-line therapy, and is comparable or superior to other platinum-based chemotherapy options.

The drug has a manageable toxicity profile and has shown promising results when combined with novel targeted agents in Phase II studies, indicating its versatility in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. Wakelee, H., Ramalingam, S., Belani, CP.[2018]

Recent advancements in pharmacogenomics have led to the development of novel agents for treating non-small cell lung cancer adenocarcinoma, emphasizing the importance of testing for specific mutations like EGFR and ALK in clinical practice.

Immunotherapy, particularly with agents like nivolumab and pembrolizumab, has emerged as a promising treatment for advanced non-small cell lung cancer, although monitoring for adverse effects is crucial during patient follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases. Zarogoulidis, P., Chinelis, P., Athanasiadou, A., et al.[2020]

In a phase 3 trial involving 423 patients with untreated stage IV or recurrent non-small-cell lung cancer (NSCLC) and PD-L1 expression of 5% or more, nivolumab did not show a significant improvement in progression-free survival compared to chemotherapy, with median times of 4.2 months versus 5.9 months, respectively.

Nivolumab demonstrated a better safety profile than chemotherapy, with 71% of patients experiencing treatment-related adverse events compared to 92% in the chemotherapy group, and significantly fewer severe adverse events (grade 3 or 4) at 18% versus 51%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. Carbone, DP., Reck, M., Paz-Ares, L., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06472076

NCT06472076 | A Study of Belrestotug Plus Dostarlimab ... The goal of this clinical trial is to evaluate the safety and tolerability profile of dostarlimab in combination with belrestotug when compared with ...

2. onclive.com onclive.com/view/frontline-belrestotug-dostarlimab-boosts-responses-vs-dostarlimab-alone-in-pd-l1-high-nsclc

Frontline Belrestotug/Dostarlimab Boosts Responses Vs ... Treatment with belrestotug plus dostarlimab yielded a clinically meaningful improvement in ORR vs dostarlimab monotherapy in unresectable PD-L1–high NSCLC.

3. targetedonc.com targetedonc.com/view/belrestotug-program-terminated-after-mixed-phase-2-results-in-nsclc

Belrestotug Program Terminated After Mixed Phase 2 ... Belrestotug plus dostarlimab showed no progression-free survival benefit in NSCLC, leading GSK and iTeos to discontinue all development and ongoing trials.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03874-2/fulltext

LBA52 Interim analysis of GALAXIES Lung-201 At this IA, belrestotug + dostarlimab demonstrated clinically meaningful anti-tumor activity at each dose and a manageable safety profile, supporting further ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03739710

Study Details | NCT03739710 | Platform Trial of Novel ... Part 2 is a randomized, Phase II open-label part comparing the efficacy and safety of these novel regimens with SoC. Drug name mentioned as GSK4428859A ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04446351

NCT04446351 | Study of the Safety and Effectiveness ... This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical ...