Novel Drug Regimens for Lung Cancer

Recruiting at 64 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

176 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new treatment plans that include a drug called belrestotug. It targets patients with advanced lung cancer that has come back or hasn't responded to other treatments. The goal is to see if these new plans work better than the usual treatments.

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.

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

Research shows that combining docetaxel with PD-1/PD-L1 inhibitors can improve outcomes for patients with advanced non-small cell lung cancer (NSCLC), suggesting potential benefits of similar combinations in the trial. Additionally, docetaxel alone has demonstrated survival benefits in NSCLC treatment. ^{1 2 3 4 5}

What safety data exists for docetaxel in lung cancer treatment?

Docetaxel has been studied in combination with other drugs for treating advanced non-small cell lung cancer, and these studies have evaluated its safety. It has been compared to other treatments, and while it is generally considered safe, like all medications, it can have side effects. ^{1 4 6 7 8}

What makes the drug regimen for lung cancer unique?

This novel drug regimen for lung cancer combines multiple agents, including Cobolimab, Dostarlimab, and Niraparib, which are not typically used together in standard treatments. These drugs target different pathways, potentially offering a more comprehensive approach to treating lung cancer compared to traditional chemotherapy alone. ^{1 2 9 10 11}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[A randomized phase II trial of docetaxel and doxorubicin in treatment for patients with non-small-cell lung cancer who have failed previous platinum-based chemotherapy]. [2018]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Addition of Anti-PD1 to Chemotherapy in Treatment of Non-Small Cell Lung Cancer. [2019]

3. China 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]. [2022]

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

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. [2018]

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

Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. [2018]

7. England 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). [2020]

8. England pubmed.ncbi.nlm.nih.gov

Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases. [2020]

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

Docetaxel (Taxotere) as a single agent and in combination chemotherapy for the treatment of patients with advanced non-small cell lung cancer. [2018]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. [2019]