TY-2136b for Solid Tumors

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TYK Medicines, Inc

Must not be taking: Immunosuppressants, Anti-arrhythmics, PPIs, others

Disqualifiers: Symptomatic CNS metastases, Cardiovascular disease, Active infections, others

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

Compensation: Varies

Number of Visits: 1

282 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate the safety and tolerability of TY-2136b and to determine the recommended phase 2 dose (RP2D), with dose-escalation stage and dose-expansion stage.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as strong inhibitors or inducers of specific enzymes (CYP3A, P-glycoprotein) and proton pump inhibitors, before starting the study drug. If you're on these medications, you may need to stop them 2 weeks or a few days before the trial, depending on the type.

What data supports the effectiveness of the drug TY-2136b for solid tumors?

The research highlights that drugs targeting the ErbB protein family, like tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, have shown effectiveness in treating various solid tumors, including lung and breast cancer. These drugs work by blocking signals that help cancer cells grow and survive, suggesting that similar mechanisms might support the effectiveness of TY-2136b. ^{1 2 3 4 5}

What makes the drug TY-2136b unique for treating solid tumors?

TY-2136b is a novel treatment for solid tumors, potentially involving a unique mechanism of action or targeting specific pathways not addressed by existing therapies. While specific details about TY-2136b are not provided, it may share similarities with other targeted therapies like tyrosine kinase inhibitors, which block specific proteins involved in cancer cell growth. ^{3 6 7 8 9}

Research Team

TYK Medicines, Inc

Principal Investigator

TYK Medicines, Inc

Eligibility Criteria

Adults with advanced solid tumors and specific genetic changes (ALK, ROS1, NTRK1-3) who've tried standard treatments without success or can't tolerate them. They must be able to swallow tablets, have a life expectancy of at least 3 months, use effective contraception if of childbearing potential, and not have symptomatic brain metastases or certain lung diseases.

Inclusion Criteria

I am 18 years old or older.

At least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumor Version 1.1 (RECIST v1.1)

I have had chemotherapy or immunotherapy for cancer before.

Exclusion Criteria

Concurrent participation in another therapeutic clinical trial, unless in follow-up period of a previous interventional clinical trial

I haven't had serious heart problems in the last 6 months.

I haven't had major surgery in the last 4 weeks or radiation therapy in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Multiple doses of TY-2136b are administered to find the maximum tolerated dose

28 days

Cycle 1 Day 1 and Cycle 1 Day 21 (at pre-dose, 0.5, 1, 2, 4, 6, 24 hours post-dose)

Dose Expansion

4 distinct expansion cohorts receive TY-2136b to evaluate safety and efficacy

Up to 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TY-2136b

Trial Overview The trial is testing the safety and ideal dosage of TY-2136b in two stages: dose escalation to find the safe maximum dose and dose expansion to study its effects more broadly. Participants will take TY-2136b to see how it affects their tumors.

Participant Groups

Group I: Expansion stage Experimental Treatment 1 Intervention

Expansion stage: 4 distinct expansion cohorts

Group II: Escalation stage Experimental Treatment 1 Intervention

Escalation stage: Multiple doses of TY-2136b for oral administration to find the maximum tolerated dose

Who Is Running the Clinical Trial?

TYK Medicines, Inc

Lead Sponsor

Trials

13

Recruited

2,300+

Findings from Research

Imatinib is an effective tyrosine kinase inhibitor that targets specific pathways involved in cancer, showing significant activity in chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GISTs), with response rates over 50% in clinical trials.

In large randomized trials, imatinib demonstrated a higher complete hematological and cytogenetic response rate compared to traditional treatments for CML, and higher doses were associated with improved progression-free survival, highlighting its potential as a targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development and application of imatinib. Jones, RL., Judson, IR.[2019]

ErbB signaling plays a crucial role in the development of many solid cancers, leading to the creation of targeted therapies like monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) for treatment.

Despite their effectiveness, both mAbs and TKIs face challenges with cancer resistance, prompting a shift towards combination therapies as a promising strategy for improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ErbB antagonists patenting: "playing chess with cancer". Aifa, S., Rebai, A.[2019]

Gefitinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), has shown significant efficacy in treating non-small-cell lung cancer (NSCLC), leading to its FDA approval for this refractory disease.

In combination with standard chemotherapy, gefitinib has demonstrated improved response rates in colorectal cancer (75% vs. 55%) and has a mild toxicity profile, making it a promising addition to cancer treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefitinib (Iressa, ZD1839) and tyrosine kinase inhibitors: the wave of the future in cancer therapy. Penne, K., Bohlin, C., Schneider, S., et al.[2019]

Overactivation of the ErbB protein family is linked to various cancers, leading to the development of targeted therapies like EGFR and HER2 inhibitors, which have shown clinical activity in treating non-small cell lung cancer (NSCLC) and breast cancer.

Agents such as afatinib, dacomitinib, and neratinib are currently in advanced clinical trials, with afatinib already approved for EGFR mutation-positive NSCLC, indicating promising efficacy for these targeted treatments in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer. Subramaniam, D., He, AR., Hwang, J., et al.[2019]

Erlotinib demonstrated a disease control rate of 52.5% in patients with non-small cell lung cancer who previously responded to gefitinib, indicating it can be an effective treatment option after gefitinib failure.

There was no significant difference in efficacy between patients who received erlotinib immediately after gefitinib failure and those who had chemotherapy in between, suggesting flexibility in treatment sequencing for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of erlotinib after the failure of gefitinib in patients with metastasis of non-small cell lung cancer with unknown EGFR mutation status]. Wang, Y., Li, JL., Wang, ZP., et al.[2018]

Afatinib is an irreversible blocker of the ErbB family of receptors that has shown strong anti-tumor effects in preclinical studies and clinical efficacy in patients with non-small-cell lung cancer, as well as activity in head and neck squamous cell carcinoma and breast cancer.

The development of afatinib is particularly important as it addresses the growing issue of treatment resistance seen with existing therapies targeting ErbB signaling, offering a potential new option for patients with these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and clinical development of afatinib: a focus on breast cancer and squamous cell carcinoma of the head and neck. Harbeck, N., Solca, F., Gauler, TC.[2019]

Gefitinib is an orally active EGFR-tyrosine kinase inhibitor that effectively blocks cancer cell growth by interfering with signaling pathways, and it has been approved for use in several countries since the early 2000s.

Current clinical trials are exploring gefitinib's efficacy across various solid tumors, including non-small-cell lung cancer and breast cancer, both as a standalone treatment and in combination with other therapies, highlighting its potential to improve cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefitinib: current and future status in cancer therapy. Herbst, RS., Kies, MS.[2018]

Recent advances in antibody-based therapies, such as trastuzumab and bevacizumab, have shown promise in treating various solid tumors, including breast and colorectal cancers, with acceptable safety profiles.

Combining monoclonal antibodies with small-molecule inhibitors may enhance treatment efficacy and specificity, suggesting a potential direction for future cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances relating to the clinical application of naked monoclonal antibodies in solid tumors. Argyriou, AA., Kalofonos, HP.[2021]

Targeted and immunological therapies have significantly improved survival rates in patients with solid tumors, demonstrating the effectiveness of treatments that focus on specific genetic and immunological changes in tumors.

Current clinical trials are exploring the optimal timing and sequencing of these therapies, which include various approved agents for cancers like prostate, breast, lung, and melanoma, indicating a shift towards more personalized cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. Grünwald, V., Rickmann, M.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

The development and application of imatinib. [2019]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

ErbB antagonists patenting: "playing chess with cancer". [2019]

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

Gefitinib (Iressa, ZD1839) and tyrosine kinase inhibitors: the wave of the future in cancer therapy. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer. [2019]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy of erlotinib after the failure of gefitinib in patients with metastasis of non-small cell lung cancer with unknown EGFR mutation status]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Preclinical and clinical development of afatinib: a focus on breast cancer and squamous cell carcinoma of the head and neck. [2019]

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

Gefitinib: current and future status in cancer therapy. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Recent advances relating to the clinical application of naked monoclonal antibodies in solid tumors. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]