TSR-022 for Advanced Cancer

Recruiting in Palo Alto (17 mi)

+50 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: GlaxoSmithKline

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Steroids

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

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing TSR-022, a new medicine that helps the immune system fight cancer by blocking a protein called TIM-3. TIM-3 has gained prominence as a potential candidate for cancer immunotherapy, where it has been shown that blocking TIM-3 with other treatments enhances the body's ability to fight tumors and suppress their growth. It targets patients with tumors, especially those who may not respond to standard treatments. The goal is to see if this medicine can help the immune system better attack cancer cells.

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.

What safety data exists for TSR-022 (Cobolimab) in humans?

The research articles do not provide specific safety data for TSR-022 (Cobolimab) in humans, but they discuss its potential in enhancing anti-tumor immunity and its role in cancer immunotherapy. ^{1 2 3 4 5}

How is the drug TSR-022 (Cobolimab) unique compared to other treatments for advanced cancer?

TSR-022 (Cobolimab) is unique because it targets TIM-3, a protein that can suppress the immune system's ability to fight cancer, making it a novel approach in cancer immunotherapy. This mechanism of action is different from other treatments that may target different pathways or proteins involved in cancer progression. ^{6 7 8 9 10}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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.

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• TSR-022 (Monoclonal Antibodies)

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).

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

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

Identification and characterization of M6903, an antagonistic anti-TIM-3 monoclonal antibody. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Tim-3 finds its place in the cancer immunotherapy landscape. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Tim-3 and its role in regulating anti-tumor immunity. [2022]

6. United States 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. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A new format of single chain tri-specific antibody with diminished molecular size efficiently induces ovarian tumor cell killing. [2006]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Development of a fully human anti-GITR antibody with potent antitumor activity using H2L2 mice. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Therapeutic effect of ansamitocin targeted to tumor by a bispecific monoclonal antibody. [2019]