MYTX-011 for Lung Cancer

Recruiting at 72 trial locations

Overseen By William T Downing

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mythic Therapeutics

Disqualifiers: CNS metastases, Interstitial lung disease, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing MYTX-011, a new medication that targets advanced lung cancer cells with specific genetic markers. It uses an antibody to guide a powerful drug directly to the cancer cells to kill them.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug MYTX-011 for lung cancer?

The research does not provide direct information about MYTX-011, but studies on similar treatments like paclitaxel and carboplatin show they are used in treating advanced non-small cell lung cancer, suggesting potential effectiveness for MYTX-011 if it shares similar properties. ^{1 2 3 4 5}

What safety data exists for MYTX-011 in humans?

MYTX-011, which works by blocking PD-1/PD-L1, has been studied for safety in lung cancer. Some people experience side effects like pneumonitis (lung inflammation) and other immune-related issues, but these are generally manageable with proper care. ^{6 7 8 9 10}

Research Team

Ting Wu, MD MSc

Principal Investigator

Mythic Therapeutics

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) who have tried standard treatments. They must have measurable tumors, acceptable organ function, and agree to use birth control. People can't join if they've had recent major surgery, untreated brain metastases, significant liver disease, active infections needing IV treatment, or certain lung conditions.

Inclusion Criteria

My advanced lung cancer has been confirmed and I've tried all standard treatments.

My cancer does not have treatable EGFR mutations but may have other mutations.

My squamous NSCLC is advanced, recurrent, or metastatic with high cMET levels.

Exclusion Criteria

I have brain metastases that haven't been treated.

My neuropathy is mild or I don't have it.

I have not had major surgery in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 assesses the safety and tolerability of MYTX-011 and identifies the dose to be studied in Part 2

Up to 21 days

Multiple visits (in-person)

Dose Expansion

Part 2 includes subjects with NSCLC with cMET overexpression or MET amplification/exon 14 skipping mutations

24 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• MYTX-011

Trial Overview The study tests MYTX-011, an antibody-drug conjugate targeting cMET in NSCLC. It's given to see how safe it is and how well it works at different stages of the disease based on prior treatments and tumor characteristics like cMET expression levels.

Participant Groups

Group I: Part 2 Cohort E2 Experimental Treatment 1 Intervention

Part 2 Cohort E2 patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1

Group II: Part 2 Cohort E Experimental Treatment 1 Intervention

Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose.

Group III: Part 2 Cohort D Experimental Treatment 1 Intervention

Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose.

Group IV: Part 2 Cohort C Experimental Treatment 1 Intervention

Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose.

Group V: Part 2 Cohort B2 Experimental Treatment 1 Intervention

Part 2 Cohort B2 patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1

Group VI: Part 2 Cohort B Experimental Treatment 1 Intervention

Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose.

Group VII: Part 2 Cohort A Experimental Treatment 1 Intervention

Part 2 Cohort A patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1.

Group VIII: Part 1 Dose Escalation Experimental Treatment 1 Intervention

Part 1 patients will receive MYTX-011.

Who Is Running the Clinical Trial?

Mythic Therapeutics

Lead Sponsor

Trials

1

Recruited

250+

Findings from Research

In a phase II study involving 14 patients with advanced non-small cell lung cancer (NSCLC) who had already undergone multiple treatments, the combination of S-1 with either irinotecan or docetaxel did not demonstrate significant efficacy as a salvage treatment.

The median survival time for participants was only 5.6 months, and the study was halted early due to a lack of responses, indicating that this treatment approach is not recommended for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of S-1 Plus Either Irinotecan or Docetaxel for Non-small Cell Lung Cancer Patients Treated with More Than Three Lines of Treatment. Kim, DY., Lee, DH., Jang, SJ., et al.[2021]

In a study of 40 patients with completely resected stage II and IIIA non-small cell lung cancer, combining concurrent carboplatin/paclitaxel chemotherapy with thoracic radiotherapy (TRT) showed promising outcomes, with 2-year and 5-year overall survival rates of 92% and 88%, respectively.

The treatment was generally well-tolerated, with 92% of patients receiving the planned TRT doses, although some experienced significant side effects, including grade 3 esophagitis and pneumonitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of concurrent carboplatin and paclitaxel and thoracic radiotherapy for completely resected stage II and IIIA non-small cell lung cancer. Feigenberg, SJ., Hanlon, AL., Langer, C., et al.[2015]

In a randomized phase II study of 62 patients with advanced non-small cell lung cancer, the combination of larotaxel and cisplatin showed a higher objective response rate and longer progression-free survival compared to larotaxel and gemcitabine.

Both treatment combinations were manageable in terms of safety, but the larotaxel-cisplatin group had better efficacy outcomes, suggesting it may be the more promising option for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized multicenter phase II study of larotaxel (XRP9881) in combination with cisplatin or gemcitabine as first-line chemotherapy in nonirradiable stage IIIB or stage IV non-small cell lung cancer. Zatloukal, P., Gervais, R., Vansteenkiste, J., et al.[2022]

The maximum tolerated dose (MTD) for the carboplatin and paclitaxel combination was established at 235 mg/m2 and 375 mg/m2, respectively, showing a good safety profile with minimal neutropenia and no thrombocytopenia in 50 patients with advanced non-small cell lung cancer.

The treatment resulted in an overall response rate of 38%, with a median overall survival time of 51.81 weeks and a 1-year survival rate of 49%, indicating that this combination therapy is both effective and well tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II dose finding study of paclitaxel and carboplatin in advanced non-small cell lung cancer. Scagliotti, GV., Crinó, L., Pozzi, E., et al.[2019]

In a phase II study involving 20 patients with locally advanced non-small cell lung cancer, the combination of weekly paclitaxel and cisplatin with thoracic radiotherapy showed a 43.8% objective response rate, indicating some efficacy in treating this aggressive cancer.

However, the treatment was associated with a high incidence of severe toxicities (75% of patients experienced grade 3/4 side effects), leading to early discontinuation of treatment for some patients and ultimately prompting the study's closure due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of weekly paclitaxel, cisplatin and concurrent radiation therapy for locally-advanced unresectable non-small cell lung cancer: early closure due to lack of efficacy. Park, SH., Kim, MK., Kyung, SY., et al.[2021]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

In a study of 191 patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors, those who experienced immune-related adverse events (irAEs) had significantly better treatment outcomes, with an objective response rate of 42.0% compared to 25.8% in those without irAEs.

The presence of irAEs was associated with improved progression-free survival, suggesting that these adverse events may indicate a more effective immune response to the treatment, although they did not correlate with overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China. Chen, X., Nie, J., Dai, L., et al.[2022]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

In a study of 66 patients with operable stage III non-small cell lung cancer (NSCLC), the combination of Camrelizumab with Docetaxel and Cisplatin showed good overall safety, with most adverse events (AEs) being mild (grade 1-2) and only 9.1% being severe (grade 3-4).

The supervision of adverse events during neoadjuvant therapy not only helped in managing complications but also led to an improvement in patients' quality of life, indicating that careful monitoring can enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC]. Zhang, Y., Zhou, S., Tao, W., et al.[2023]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase II Study of S-1 Plus Either Irinotecan or Docetaxel for Non-small Cell Lung Cancer Patients Treated with More Than Three Lines of Treatment. [2021]

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

A phase II study of concurrent carboplatin and paclitaxel and thoracic radiotherapy for completely resected stage II and IIIA non-small cell lung cancer. [2015]

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

Randomized multicenter phase II study of larotaxel (XRP9881) in combination with cisplatin or gemcitabine as first-line chemotherapy in nonirradiable stage IIIB or stage IV non-small cell lung cancer. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Phase I/II dose finding study of paclitaxel and carboplatin in advanced non-small cell lung cancer. [2019]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

A phase II study of weekly paclitaxel, cisplatin and concurrent radiation therapy for locally-advanced unresectable non-small cell lung cancer: early closure due to lack of efficacy. [2021]

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

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021]

9. China pubmed.ncbi.nlm.nih.gov

[Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC]. [2023]

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

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. [2022]