GT103 + Pembrolizumab for Lung Cancer

No longer recruiting at 5 trial locations

Overseen By Jeffrey Clarke, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jeffrey Clarke

Must not be taking: Anticancer therapies, Immunosuppressants

Disqualifiers: Auto-immune conditions, Pneumonitis, HIV, 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: 21

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with advanced lung cancer that hasn't responded to other treatments. Researchers aim to determine if GT103 (an experimental treatment) combined with pembrolizumab (an immunotherapy drug) is safe and tolerable for patients. This combination targets those whose cancer has returned or hasn't improved after previous immunotherapy or chemotherapy. It suits individuals with metastatic lung cancer who have tried up to two previous treatments but still need new options. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering access to potentially effective new therapies.

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 mention that you cannot be on certain anticancer therapies or medications that suppress the immune system beyond a certain level. It's best to discuss your specific medications with the trial team.

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

Research has shown that combining GT103 and pembrolizumab is generally safe and well-tolerated. Earlier studies did not reveal any new safety issues with this treatment, and some patients experienced long-lasting benefits. The FDA has already approved pembrolizumab for other uses, indicating its well-established safety. Overall, data from other studies suggest that the combination appears safe. ^{1 2 3 4 5}

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

Researchers are excited about the combination of GT103 and pembrolizumab for lung cancer because it potentially enhances the immune system's ability to fight tumors. Pembrolizumab is an established immunotherapy that blocks a specific protein to help the immune system attack cancer cells. GT103 is unique because it targets a different pathway, potentially boosting pembrolizumab's effectiveness. This combination aims to offer a more robust response than existing treatments like chemotherapy and radiation, which often come with significant side effects. By working together, these drugs could provide a more targeted and less toxic approach to treating lung cancer.

What evidence suggests that this treatment might be an effective treatment for lung cancer?

Research has shown that using GT103 with pembrolizumab, the combination studied in this trial, may help treat certain types of non-small cell lung cancer (NSCLC). Studies have found this combination to be generally safe for patients, without causing new safety issues. Some patients have experienced lasting benefits, with their cancer either stopping growth or shrinking for extended periods. Pembrolizumab is already known to enhance the immune system's ability to fight lung cancer. While further research is needed, these results offer hope that the GT103 and pembrolizumab combination could be an effective treatment option. ^{1 3 6 7 8}

Who Is on the Research Team?

Jeffrey M. Clarke

Principal Investigator

Duke Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with Stage III-IV recurrent or metastatic NSCLC, who have relapsed or are refractory to immunotherapy and possibly chemotherapy. They must have adequate organ function, not be pregnant or breastfeeding, use contraception if of childbearing potential, and cannot have other conditions that might interfere with the trial.

Inclusion Criteria

Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to C1D1.

Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception as outlined in protocol.

As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria

Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.

Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

You cannot tolerate pembrolizumab or other drugs that help the immune system fight cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A safety lead-in phase to determine the safest dose of GT103 in combination with pembrolizumab

6 months

Regular visits as per protocol

Treatment

Participants receive GT103 and pembrolizumab intravenously on Day 1 of a 21-day cycle

3 years

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• GT103
• Pembrolizumab

Trial Overview The trial is testing GT103 in combination with Pembrolizumab for safety and effectiveness in treating NSCLC. It includes an initial phase to determine the safest dose followed by treatment of up to 60 patients at this dose level.

How Is the Trial Designed?

Group I: Experimental Group Experimental Treatment 2 Interventions

Pembrolizumab will be given intravenously on Day 1 of the 21 day cycle (For all cycles). GT103 dose will be determined by the safety lead in prior to the study. Dosing calculations should be based on actual body weight where applicable. It will be taken intravenously on Day 1 of the 21 day cycle (For all cycles).

Who Is Running the Clinical Trial?

Jeffrey Clarke

Lead Sponsor

Jeffrey Clarke

Lead Sponsor

Trials

4

Recruited

110+

Grid Therapeutics

Industry Sponsor

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Grid Therapeutics

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07017829

Study Details | NCT07017829 | GT103 in Combination With ... This phase II trial tests how well GT103 in combination with pembrolizumab works in treating patients with STK11 mutant non-small cell lung cancer that may ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41129008/

A Phase II study of GT103 in combination with ... Combination of GT103 with pembrolizumab was well tolerated with no new safety signals. A subset of patients experienced durable responses and disease ...

3. trial.medpath.com trial.medpath.com/clinical-trial/6d62f7475863d3e4/nct07017829-gt103-pembrolizumab-stk11-mutant-nsclc

GT103 in Combination With Pembrolizumab for the Treatment ... This phase II trial tests how well GT103 in combination with pembrolizumab works in treating patients with STK11 mutant non-small cell lung cancer that may ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05617313

Study of GT103 in Combination With Pembrolizumab ... This open-label, non-randomized Phase II trial is designed to assess the safety and tolerability of GT103 in combination with pembrolizumab in adult ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40157574/

the phase III 3475A-D77 trial Conclusions: Overall exposure and trough concentrations of pembrolizumab s.c. 790 mg q6w were noninferior to those of pembrolizumab i.v. 400 mg q6w given with ...

6. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70141?af=R

A Phase II study of GT103 in combination with pembrolizumab ... A single arm, Simon two-stage, Phase II study was conducted that evaluated efficacy and safety of GT103 plus pembrolizumab in patients with ...

7. jitc.bmj.com jitc.bmj.com/content/12/Suppl_3/A1717?rss=1

1487 Results from a phase II study of GT103 in ... A phase I trial of GT103 monotherapy has demonstrated the therapy to be well tolerated in advanced NSCLC patients. Preclinical data suggests combination with ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-01818

GT103 and Pembrolizumab for the Treatment of Patients ... Giving GT103 with pembrolizumab may kill more cancer cells and improve outcomes in patients with recurrent or refractory metastatic non-small cell lung cancer.