GSK4381562 for Cancer

Recruiting at 21 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: Organ transplant, Recent malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

158 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, GSK4381562, for individuals with certain solid tumors that have returned or spread after other treatments failed. The goal is to determine the safety of this treatment and its behavior in the body. Participants will receive either GSK4381562 alone or with other drugs to explore different treatment effects. This trial suits those with head and neck, lung, breast, kidney, stomach, colorectal, endometrial, or ovarian cancers that did not respond to standard therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain prior treatments and therapies are not allowed within specific time frames before starting the study. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that GSK4381562 is being tested in humans for the first time, so limited information exists about its safety. As this is an early-stage study, researchers are carefully monitoring for any side effects.

Dostarlimab, however, has more safety information available. The FDA has approved it for treating certain cancers, such as endometrial cancer, indicating it has generally been well-tolerated in past studies. Some patients have used dostarlimab for over a year with manageable side effects.

For combinations like GSK4381562 with dostarlimab, and other drug mixes in the trial, detailed safety information is still being gathered. Dostarlimab and belrestotug have been studied together before, showing promise in other cancers with tolerable side effects.

Overall, for those considering joining the trial, the existing safety evidence for dostarlimab is reassuring, but the safety of GSK4381562 is still under exploration. Researchers will closely monitor participants to manage any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GSK4381562 for cancer because it offers a novel approach compared to current treatments like chemotherapy and immunotherapy. Unlike traditional therapies, GSK4381562 may work by targeting specific pathways that cancer cells use to grow, potentially leading to more effective outcomes with fewer side effects. Additionally, when combined with other agents like dostarlimab and belrestotug, it aims to enhance the body's immune response against cancer cells, offering a promising synergistic effect. This innovative mechanism of action sets it apart from existing options, providing hope for improved cancer treatment.

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

Research has shown that GSK4381562, a new treatment tested in this trial, aims to strengthen the body's immune system to fight cancer. Early studies suggest it could improve outcomes for some difficult-to-treat cancers. Participants in this trial may receive GSK4381562 alone or with other drugs. Dostarlimab, one of the drugs used, has already delivered impressive results, with some patients showing no signs of disease after treatment. When combined with other drugs like belrestotug, as in some trial arms, it has shown promise in treating cancers such as non-small cell lung cancer. This drug combination aims to be more effective by attacking cancer cells in different ways. Overall, initial findings suggest potential benefits in treating various advanced cancers. ^{1 3 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, like lung, breast, or colorectal cancer, that have worsened after standard treatments or when such treatments aren't suitable. Participants must not be pregnant or breastfeeding and should use effective contraception. They need to have a life expectancy of at least 12 weeks and good organ function.

Inclusion Criteria

I agree to have two tumor biopsies: one before and one 6 weeks after starting treatment.

I am not pregnant or breastfeeding.

My organs are functioning well.

Exclusion Criteria

I have experienced side effects from previous cancer treatments.

I have another cancer that has worsened or needed treatment in the last 2 years.

My side effects from previous treatments have mostly gone away.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GSK4381562 as monotherapy or in combination with other anticancer agents

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term follow-up

Participants are monitored for long-term safety and overall response rate

27 months

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• GSK4381562
• GSK4428859A

Trial Overview The study tests GSK4381562's safety and effects in humans for the first time. It will also look at how the body processes it (pharmacokinetics) and if it triggers immune responses (immunogenicity). Dostarlimab and GSK4428859A are other interventions under investigation.

How Is the Trial Designed?

Group I: Participants receiving dostarlimab plus belrestotug plus nelistotug (Arm F) Experimental Treatment 3 Interventions

Group II: Participants receiving dostarlimab plus belrestotug plus GSK4381562 (Arm E) Experimental Treatment 3 Interventions

Group III: Participants receiving dostarlimab plus belrestotug (Arm D) Experimental Treatment 2 Interventions

Group IV: Participants receiving GSK5764227 plus dostarlimab (Arm I) Experimental Treatment 2 Interventions

Group V: Participants receiving GSK4381562 plus dostarlimab plus belrestotug (Arm C) Experimental Treatment 3 Interventions

Group VI: Participants receiving GSK4381562 plus dostarlimab (Arm B) Experimental Treatment 2 Interventions

Group VII: Participants receiving GSK4381562 monotherapy (Arm A) Experimental Treatment 1 Intervention

Group VIII: China Cohort: Participants receiving dostarlimab plus belrestotug (Arm H) Experimental Treatment 2 Interventions

Group IX: China Cohort: Participants receiving dostarlimab (Arm G) Experimental Treatment 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

Published Research Related to This Trial

SGI-1776 demonstrated significant anti-tumor effects on human ovarian cancer HO-8910 cells, inhibiting cell proliferation, migration, and invasion in a dose-dependent manner, and causing cell cycle arrest in the G1 phase.

The mechanism of action involves the down-regulation of Pim-1 kinase activity and its downstream targets, indicating that Pim-1 could be a potential therapeutic target for treating ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGI-1776, an imidazo pyridazine compound, inhibits the proliferation of ovarian cancer cells by inactivating Pim-1. Xie, J., Bai, J.[2018]

Elraglusib, a GSK-3 inhibitor, enhances immune cell-mediated killing of colorectal cancer (CRC) cells by sensitizing them to immune attacks and promoting immune cell function, which could improve treatment outcomes.

In a murine model, elraglusib combined with immune checkpoint blockade (anti-PD-1/L1) led to improved survival rates, increased tumor-infiltrating T cells, and a favorable shift in cytokine profiles, suggesting its potential as an effective therapy for CRC and possibly other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GSK-3 Inhibitor Elraglusib Enhances Tumor-Infiltrating Immune Cell Activation in Tumor Biopsies and Synergizes with Anti-PD-L1 in a Murine Model of Colorectal Cancer. Huntington, KE., Louie, AD., Srinivasan, PR., et al.[2023]

GSK-3β mutations were found in about 1% of over 100,000 tumors analyzed, with uterine endometrioid carcinoma showing the highest mutation rate at 4%, indicating its potential role in cancer development.

Tumors with GSK-3β mutations exhibited increased PD-L1 expression and a higher infiltration of immune cells, suggesting that these mutations may influence the tumor microenvironment and immune response, which could have implications for targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Landscape of Glycogen Synthase Kinase-3 Beta Genomic Alterations in Cancer. Borden, BA., Baca, Y., Xiu, J., et al.[2021]

NT157, a tyrosine kinase inhibitor, effectively inhibits glioma cell growth in vitro by causing cell cycle arrest and inducing apoptosis through mechanisms involving p21, p27, and the DR5 pathway.

Combining NT157 with TRAIL enhances apoptosis in glioma cells and significantly reduces tumor growth in vivo, suggesting that this combination therapy could be a promising strategy for treating human glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NT157 inhibits cell proliferation and sensitizes glioma cells to TRAIL-induced apoptosis by up-regulating DR5 expression. Hou, YJ., Li, D., Wang, W., et al.[2022]

LKB1/KRAS mutant non-small-cell lung cancer (NSCLC) cell lines show a significant sensitivity to the MEK inhibitor CI-1040, indicating a potential targeted treatment option for this specific cancer subtype.

These LKB1/KRAS mutant NSCLCs are also responsive to the mTOR inhibitor rapamycin, suggesting that targeting both the MAPK and mTOR pathways could be an effective therapeutic strategy for this genetically distinct group of lung cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition. Mahoney, CL., Choudhury, B., Davies, H., et al.[2022]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05565378

NCT05565378 | A Platform Study of Novel Immunotherapy ... This study will monitor the safety of novel immunotherapy combinations in participants with Programmed death ligand-1 (PD L-1) high (Tumor cells [TC]/ Tumor ...

3. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2021-005115-32/FI

Clinical Trials Register The European Union Clinical Trials Register allows you to search for protocol and results information on EU/EEA interventional clinical trials.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-of-eos884448-dostarlimab-and-inupadenant-for-patients-with-advanced-solid-tumors/

Study of EOS884448, Dostarlimab, and Inupadenant for ... This clinical trial tests the efficacy and safety of EOS884448, Dostarlimab, and Inupadenant in treating patients with advanced solid tumors ...

5. gsk.com gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-trial-continues-to-show-unprecedented-results/

Jemperli (dostarlimab) trial continues to show ... These results bring us one step closer to understanding the potential of dostarlimab in this curative-intent setting for patients with dMMR ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03739710

Study Details | NCT03739710 | Platform Trial of Novel ... Part 1: Participants receiving dostarlimab plus GSK4428859A/EOS884448/belrestotug plus GSK6097608, Intervention/Treatment, Drug : GSK4428859A ... safety data of ...

7. gsk.com gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-receives-us-fda-breakthrough-therapy-designation-for-locally-advanced-dmmrmsi-h-rectal-cancer/

Jemperli (dostarlimab) receives US FDA Breakthrough ... Designation based on data showing no evidence of disease in 100% of all 42 patients who completed treatment with dostarlimab.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761174s000lbl.pdf

JEMPERLI (dostarlimab - accessdata.fda.gov Among the 444 patients, 38% were exposed for >6 months and 12% were exposed for >1 year. Mismatch Repair Deficient (dMMR) Endometrial Cancer. The safety of ...