TSR-022 for Advanced Cancer

Recruiting at 50 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Uncontrolled CNS metastases, Active infection, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

475 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TSR-022 (an anti-TIM-3 antibody) for individuals with advanced cancers, including melanoma, non-small cell lung cancer, colorectal cancer, and hepatocellular carcinoma. The main goal is to determine the optimal dose and evaluate its effectiveness against tumors, both alone and in combination with other treatments like TSR-042 or docetaxel. The trial seeks participants with tumors that are inoperable or have metastasized, and who have undergone specific previous cancer treatments. This study involves different groups, each testing TSR-022 alone or with other drugs. 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 this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, participants must not be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study treatment. It's best to discuss your current medications with the study team to ensure they align with the trial requirements.

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

Research has shown that TSR-022, a type of antibody, was tested in earlier studies. Used alone or with other drugs like TSR-042, it was generally well-tolerated by patients. Reports indicate that combining TSR-022 with TSR-042 was safe and showed early signs of tumor-fighting activity.

When combined with the chemotherapy drug docetaxel, TSR-022 also demonstrated a similar safety level. Although later testing stages for non-small cell lung cancer (NSCLC) presented some challenges, earlier studies did not find major safety issues. TSR-022, when used with another drug, nivolumab, was also tolerated by patients and showed some early positive effects.

Overall, these findings suggest that TSR-022, whether used alone or with other drugs, has been manageable in terms of safety in the studies so far. However, as this is a Phase 1 trial, it remains early in the research process. The main goal is to determine a safe dose for future studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

TSR-022 is unique because it targets the TIM-3 pathway, a mechanism not commonly addressed by standard cancer treatments like chemotherapy or PD-1 inhibitors. This approach may help the immune system more effectively recognize and fight cancer cells. Researchers are excited about combining TSR-022 with other drugs like TSR-042, as this could enhance its effectiveness, providing a new synergy in attacking cancer. This combination could potentially offer a more comprehensive treatment strategy for tough cancers like melanoma, non-small cell lung cancer, and colorectal cancer.

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

Research has shown that TSR-022, a type of antibody, may effectively treat cancer. In this trial, participants will receive TSR-022 either as monotherapy or combined with other treatments. Some participants will receive TSR-022 with TSR-042, another cancer therapy that has shown promise in shrinking tumors in patients with cancers such as non-small cell lung cancer. Others will receive TSR-022 combined with the chemotherapy drug docetaxel, which has shown some potential in fighting cancer, although recent trials for this combination encountered difficulties. These findings offer hope that TSR-022 could be a valuable treatment option for people with advanced cancers. ^{2 3 4 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors. Participants must meet certain health criteria to join, but specific inclusion and exclusion details are not provided here.

Inclusion Criteria

Negative human immunodeficiency virus (HIV) test at screening

Participant has measurable disease as per RECIST v1.1.

Documented hepatitis C virus (HCV) antibody testing conducted at screening. If HCV antibody is positive, then hepatitis C virus ribonucleic acid (HCV ribonucleic acid (RNA) must be negative.

Exclusion Criteria

I finished palliative radiotherapy less than a week ago.

Participant is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment.

Participant must not have a known hypersensitivity to TSR-042 and TSR-022 components or excipients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 of the study involves dose escalation to determine the recommended Phase 2 dose (RP2D) of TSR-022

Up to 42 days

Dose Expansion

Part 2 of the study evaluates the antitumor activity of TSR-022 in combination with TSR-042 or docetaxel and as monotherapy

Up to 2 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

• TSR-022

Trial Overview The study tests TSR-022, an antibody targeting TIM-3 in the immune system. It's a two-part study: first finding the right dose (dose escalation) and then testing its effectiveness alone or with other drugs like TSR-042 or docetaxel (dose expansion).

How Is the Trial Designed?

Group I: Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042 Experimental Treatment 2 Interventions

Group II: Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy Experimental Treatment 1 Intervention

Group III: Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy Experimental Treatment 1 Intervention

Group IV: Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042 Experimental Treatment 2 Interventions

Group V: Part 2: Cohort F- Hepatocellular carcinoma (HCC)-TSR-022 with TSR-042 Experimental Treatment 2 Interventions

Group VI: Part 2: Cohort E-Non-small cell lung cancer-TSR-022 with docetaxel Experimental Treatment 2 Interventions

Group VII: Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)-TSR-022 with TSR-042 Experimental Treatment 2 Interventions

Group VIII: Part 2: Cohort A Melanoma-TSR-022 with TSR-042 Experimental Treatment 2 Interventions

Group IX: Part 2: Cohort A Melanoma-TSR-022 as monotherapy Experimental Treatment 1 Intervention

Group X: Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin Experimental Treatment 4 Interventions

Group XI: Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin Experimental Treatment 4 Interventions

Group XII: Part 1f: TSR-022 in combination with TSR-042 and Docetaxel Experimental Treatment 3 Interventions

Group XIII: Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1) Experimental Treatment 2 Interventions

Group XIV: Part 1d: TSR-022 in combination with TSR-042 and TSR-033 Experimental Treatment 3 Interventions

Group XV: Part 1c: TSR-022 in combination with TSR-042 Experimental Treatment 2 Interventions

Group XVI: Part 1b: TSR-022 in combination with nivolumab Experimental Treatment 2 Interventions

Group XVII: Part 1a: TSR-022 monotherapy 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

Immunotherapy, particularly targeting immune checkpoint molecules like CTLA-4 and PD-1, has shown promise in treating certain cancers, but many, including colorectal cancer, still do not respond well to these treatments.

Tim-3 is emerging as a potential target for enhancing cancer immunotherapy, as blocking Tim-3 has been shown to improve anti-tumor immunity and reduce tumor growth in various preclinical models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tim-3 and its role in regulating anti-tumor immunity. Das, M., Zhu, C., Kuchroo, VK.[2022]

Novel monoclonal antibodies targeting TIM-3 and TIM-4 significantly enhance the effectiveness of cancer vaccines against established B16 murine melanomas, suggesting a new approach to improve cancer immunotherapy.

The combination of anti-TIM-3 and anti-TIM-4 mAbs not only boosts vaccine-induced antitumor responses but also reveals distinct mechanisms of action, with TIM-3 blockade enhancing natural killer cell activity and TIM-4 primarily activating CD8(+) T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas. Baghdadi, M., Nagao, H., Yoshiyama, H., et al.[2016]

M6903 is a fully human anti-TIM-3 antibody that effectively blocks TIM-3's interaction with its ligands, leading to enhanced T cell activation, which is crucial for improving anti-tumor immunity.

The combination of M6903 with bintrafusp alfa showed superior anti-tumor efficacy in preclinical models compared to either treatment alone, suggesting a promising avenue for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification and characterization of M6903, an antagonistic anti-TIM-3 monoclonal antibody. Zhang, D., Jiang, F., Zaynagetdinov, R., et al.[2021]

The 3C10 monoclonal antibody (mAb) specifically targets the type III mutant epidermal growth factor receptor (EGFRvIII) found in certain gliomas, showing significant accumulation in tumor tissues in a study involving athymic nude mice with glioma xenografts.

The study demonstrated that 3C10 mAb has a high tumor-to-blood ratio, indicating its potential as both a diagnostic and therapeutic agent for gliomas expressing EGFRvIII, with detectable tumor localization as early as 3 hours post-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor. Takasu, S., Takahashi, T., Okamoto, S., et al.[2019]

In a phase I study involving 113 patients with advanced solid tumors, MK-4166 was found to be tolerable, with only 8% of patients experiencing treatment-related grade ≥3 adverse events and no treatment-related deaths reported.

The combination of MK-4166 with pembrolizumab showed promising efficacy, particularly in patients with immune checkpoint inhibitor (ICI)-naïve melanoma, achieving an objective response rate of 62%, indicating potential for effective treatment in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. Papadopoulos, KP., Autio, K., Golan, T., et al.[2022]

The newly developed TR3H single chain tri-specific antibody (scTsAb) effectively activates T-cells to target and kill ovarian tumor cells, demonstrating its potential as a tumor immunotherapy.

TR3H has a smaller molecular size compared to the previous scTsAb format (sTRI), which may improve its pharmacokinetics and reduce immunogenicity, making it a promising candidate for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new format of single chain tri-specific antibody with diminished molecular size efficiently induces ovarian tumor cell killing. Liu, J., Zhao, Q., Zhao, B., et al.[2006]

The study highlights the potential of targeting the glucocorticoid-induced TNF receptor-related (GITR) as a co-stimulatory receptor to enhance immunotherapy efficacy by activating T cells and reducing tumor-infiltrating Treg cells.

A newly developed fully human anti-GITR antibody, hab019e2, demonstrated superior antitumor activity in a mouse model compared to existing antibodies, suggesting it could be a promising candidate for future cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a fully human anti-GITR antibody with potent antitumor activity using H2L2 mice. Tong, Q., Liu, H., Qi, Q., et al.[2022]

A bispecific monoclonal antibody was developed that targets both ansamitocins and the human transferrin receptor, showing enhanced effectiveness in suppressing tumor growth in a mouse model of A431 epidermoid carcinoma.

This targeted approach not only improved the efficacy of ansamitocin P-3 in eradicating tumors but also reduced side effects such as weight loss, liver damage, and decreased white blood cell counts, indicating a safer treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of ansamitocin targeted to tumor by a bispecific monoclonal antibody. Okamoto, K., Harada, K., Ikeyama, S., et al.[2019]

The blockade of immune checkpoint receptors, like Tim-3 and PD-1, shows promise in reducing tumor progression and enhancing T-cell responses in cancer treatment, particularly in preclinical models.

Tim-3 is expressed by various immune cells and leukemic stem cells, indicating its potential as a target for improving therapies in cancers that currently resist treatment, such as microsatellite-stable colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tim-3 finds its place in the cancer immunotherapy landscape. Acharya, N., Sabatos-Peyton, C., Anderson, AC.[2021]

Tim-3 is recognized as a key negative regulator of immune responses, particularly affecting CD4(+) T helper 1 and CD8(+) T cytotoxic 1 cells, which are crucial for fighting infections and cancer.

Recent research indicates that Tim-3 contributes to T cell exhaustion in chronic conditions like viral infections and cancer, and it also impacts cancer outcomes by influencing myeloid cells and cancer stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tim-3, a negative regulator of anti-tumor immunity. Anderson, AC.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02817633

NCT02817633 | A Study of TSR-022 in Participants With ... This is a first-in-human study evaluating the anti-T cell immunoglobulin and mucin containing protein-3 (TIM-3) antibody TSR-022.

2. clin.larvol.com clin.larvol.com/trial-detail/NCT02817633

A Study of TSR-022 in Participants With Advanced Solid ... A phase 1 study of TSR-022, an anti-TIM-3 monoclonal antibody, in combination with TSR-042 (anti-PD-1) in patients with colorectal cancer and post-PD-1 NSCLC ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12351273/

Combined Targeting of PD-1 and TIM-3 in Patients with ... Initial results demonstrated that cobolimab in combination with dostarlimab had an acceptable safety profile and was associated with antitumor activity in ...

4. onclive.com onclive.com/view/cobolimab-dostarlimab-combination-shows-initial-efficacy-and-safety-signals-in-advanced-nsclc

Cobolimab/Dostarlimab Combination Shows Initial Efficacy ... Cobolimab plus dostarlimab-gxly showed activity and acceptable safety across all dose levels assessed in patients with non–small cell lung cancer.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2504

Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and ... Results: 104 patients (pts) were included: 1A (n=46), 1B (n=7), or 1C (n=55); 4 pts from 1A crossed over to 1C (included in 1A and 1C safety and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06322693

A Study of TSR-022 in Participants With Advanced Solid ... This is a first-in-human study evaluating the anti-T cell immunoglobulin and mucin containing protein-3 (TIM-3) antibody TSR-022.

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/gsk-anti-tim-3-antibody-fails-in-phase-iii-nsclc-trial/

GSK's anti-TIM-3 antibody fails in Phase III NSCLC trial GSK's anti-TIM monoclonal antibody (mAb) cobolimab has failed a Phase III trial in non-small cell lung cancer (NSCLC).