TSR-022 for Cancer

Not currently recruiting at 94 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tesaro, Inc.

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

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) aimed at combating various types of advanced or metastatic cancers. The study consists of two parts: the first determines the safest dose, and the second evaluates the treatment's effectiveness alone or with other cancer drugs. Individuals with advanced cancer that has spread, such as certain lung, liver, or skin cancers, and who have not responded to previous treatments, might be suitable candidates. The trial aims to determine if TSR-022 can slow or stop the growth of these difficult-to-treat cancers. 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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you must stop these at least 7 days before starting the study treatment. It's best to discuss your specific medications with the study team.

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

Research has shown that TSR-022 is still undergoing safety testing in humans. Early studies suggest that TSR-022, whether used alone or with other drugs like TSR-042 (dostarlimab), is generally well-tolerated, meaning most participants did not experience serious side effects. For instance, in studies involving patients with non-small cell lung cancer (NSCLC), the combination of TSR-022 and TSR-042 was found to be safe at various doses.

When combined with docetaxel, another cancer drug, TSR-022 was also well-tolerated and showed early signs of efficacy against tumors. The same applies to combinations with other drugs like nivolumab, pemetrexed, and cisplatin, where TSR-022 was tested for potential benefits and safety.

However, this is early-stage research focused primarily on determining the right dose and identifying any safety issues. While the results are promising, more information is needed to fully understand the safety of TSR-022 in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TSR-022 for cancer treatment because it targets the TIM-3 pathway, which is a fresh approach compared to standard treatments like chemotherapy or PD-1/PD-L1 inhibitors. Unlike traditional therapies that often attack cancer cells directly, TSR-022 works by boosting the immune system's ability to fight cancer, potentially leading to more durable responses. Additionally, when combined with other agents like TSR-042, pemetrexed, or cisplatin, TSR-022 may enhance the effectiveness of these drugs, offering a new hope for patients with difficult-to-treat cancers like non-small cell lung cancer, melanoma, and colorectal cancer.

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

Research shows that TSR-022, one of the treatments in this trial, has shown early promise in treating cancer when combined with other treatments like TSR-042 and docetaxel. This trial includes various treatment arms, such as TSR-022 with TSR-042 and docetaxel, specifically for patients with advanced cancers, including non-small cell lung cancer. Participants receiving TSR-022 and TSR-042 in this trial have shown early signs of treatment effectiveness. In other arms, TSR-022 is used alone, leading to partial improvements and stable conditions in some patients, suggesting it might help control the cancer. However, more research is needed to confirm these results and determine its true effectiveness. Overall, early signs of potential exist, but ongoing studies will provide more information. ^{3 4 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 advanced solid tumors who've had no more than two prior therapies, including a platinum-based chemo and an anti-PD-(L)1 antibody. They must have measurable disease progression, adequate organ function, ECOG performance status of 0 or 1, and a life expectancy of at least three months. Women of childbearing potential need a negative pregnancy test.

Inclusion Criteria

I've had up to 2 treatments for my advanced cancer, including platinum chemotherapy and anti-PD-1/L1 therapy.

My cancer has worsened after treatments including platinum chemotherapy and anti-PD-1 or PD-L1 therapy.

I agree to provide a tissue sample from my cancer that was not treated with radiation.

Exclusion Criteria

Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study.

My cancer has a specific change in the EGFR, ALK, or ROS-1 gene.

My cancer progressed within 8 weeks after starting treatment with a PD-1 or PD-L1 inhibitor.

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

8-12 weeks

Dose Expansion

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

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TSR-022

Trial Overview The AMBER study tests TSR-022, an anti-TIM-3 antibody for treating tumors. It has two parts: dose escalation to find the safe dosage (Part 1), and dose expansion to assess antitumor activity in combination with other drugs like TSR-042 or docetaxel or as monotherapy (Part 2).

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?

Tesaro, Inc.

Lead Sponsor

Trials

57

Recruited

10,600+

Published Research Related to This Trial

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 TIM-3 monoclonal antibody, LY3321367, demonstrated an acceptable safety profile in a phase Ia/b study with no dose-limiting toxicities observed in 30 patients receiving monotherapy and 28 patients receiving combination therapy.

While LY3321367 showed favorable pharmacokinetics and pharmacodynamics, its antitumor activity was modest, with only 4% objective response rate in combination therapy and 7% in monotherapy for patients previously treated with anti-PD-1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody. Harding, JJ., Moreno, V., Bang, YJ., et al.[2023]

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]

Bispecific antibodies (bsAbs) targeting glioblastoma-associated antigens can effectively activate T cells to kill tumor cells, with the anti-CD28 bsFab2 showing superior co-stimulation when targeting the chondroitin-sulfate proteoglycan (CSPG) due to its higher expression on the tumor surface.

The effectiveness of anti-CD3 bsFab2 is enhanced when targeting the EGF receptor (EGFR), suggesting that factors beyond just antigen expression, like membrane mobility, influence T-cell activation; this has led to the use of EGFR-targeting bsFab2 in a clinical trial for glioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of target antigen in bispecific-antibody-mediated killing of human glioblastoma cells: a pre-clinical study. Pfosser, A., Brandl, M., Salih, H., et al.[2019]

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]

The compound ML-T7 effectively targets Tim-3, enhancing the survival and antitumor activity of CD8+ T cells and CAR T cells, while also reducing T cell exhaustion in both laboratory and animal studies.

ML-T7 not only improves T cell function but also boosts the activity of natural killer (NK) cells and dendritic cells, showing comparable tumor inhibition to Tim-3 blocking antibodies and greater efficacy when combined with anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models. Ma, S., Tian, Y., Peng, J., et al.[2023]

Glofitamab, a bispecific antibody targeting CD20 and CD3, demonstrated clinical activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma during a phase 1 trial, showing T-cell activation and tumor cell killing.

The study identified that tumor intrinsic factors, such as TP53 signaling, may contribute to resistance against glofitamab, indicating that these factors could serve as important biomarkers for predicting treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Bröske, AE., Korfi, K., Belousov, A., et al.[2022]

Tim-3 is a promising new target for cancer immunotherapy, particularly in breast cancer, where its expression on both immune and tumor cells can influence treatment outcomes.

Genetic variations in the Tim-3 gene are linked to a higher risk of developing breast cancer, suggesting that targeting Tim-3 could enhance therapeutic strategies for patients who do not respond to current immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Emerging Role of T-Cell Immunoglobulin Mucin-3 in Breast Cancer: A Promising Target For Immunotherapy. Cong, Y., Liu, J., Chen, G., et al.[2021]

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]

GFRA1 has been identified as a promising tumor-associated antigen in breast cancer, showing limited expression in normal tissues but overexpression in certain breast cancer subsets, making it a potential target for treatment.

The GFRA1-targeted antibody-drug conjugate (ADC) demonstrated effective cytotoxicity in GFRA1-positive cancer cell lines and patient-derived xenograft models, with a safety profile indicating no on-target toxicity, although some transient effects were noted in bone marrow and peripheral blood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of a GFRA1 targeted antibody-drug conjugate in breast cancer. Bosco, EE., Christie, RJ., Carrasco, R., et al.[2019]

TIM-3 is expressed in tumor infiltrating lymphocytes (TILs) in all 109 samples of triple-negative breast cancer (TNBC) studied, and higher levels of TIM-3 are associated with younger patients, higher tumor stages, and increased expression of PD-1 and PD-L1.

High TIM-3 expression is linked to significantly better disease-free survival and overall survival in TNBC patients, indicating it may serve as an independent positive prognostic factor despite being associated with more aggressive disease features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer. Byun, KD., Hwang, HJ., Park, KJ., 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]

Citations

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

Cobolimab/Dostarlimab Combination Shows Initial Efficacy ... Among the 84 patients in the total study population, cobolimab plus dostarlimab elicited an overall response rate (ORR) of 8.3% (95% CI, 3.4%- ...

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

Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and ... Conclusions: Cobolimab + dostarlimab was well tolerated and showed preliminary anti-tumor activity, warranting further investigation of the RP2D ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04655976

Study Details | NCT04655976 | Efficacy Comparison of ... This is a multi-center, parallel group treatment, Phase 2/3 open label study evaluating cobolimab in combination with dostarlimab and docetaxel in participants ...

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

Combined Targeting of PD-1 and TIM-3 in Patients with ... The overall response rate (95% confidence interval) was 42.9% (24.5–62.8) and 4.7% (0.6–15.8) for patients in parts 1c/1e and 2A, respectively, and the disease ...

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

A Study of TSR-022 in Participants With Advanced Solid ... Among the 20 evaluable patients treated with the 300 milligram dose of TSR-022, 3 had confirmed partial responses and 8 had stable disease...Preliminary safety ...

6. medchemexpress.com medchemexpress.com/cobolimab.html?srsltid=AfmBOorS7DwfOsinD-yXSZ3Ej7MChG9URG03fh6IGodgnu5bqL86wraZ

Cobolimab (TSR-022) | Anti-TIM-3 mAb | MedChemExpress Cobolimab has potential application in solid tumors and non-small cell lung cancer (NSCLC). For research use only. We do not sell to patients.

7. 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.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12351275/

Combined Targeting of PD-1 and TIM-3 in Patients with ... In conclusion, the combination of cobolimab plus dostarlimab showed acceptable safety and early evidence of efficacy across three cobolimab doses in a subset of ...