Breakthrough Clinical Results
Mythic Therapeutics announced positive efficacy data from the Phase 1 KisMET-01 study of MYTX-011, a cMET-targeting antibody-drug conjugate (ADC), in patients with non-small cell lung cancer (NSCLC). The data, presented at the 2025 ASCO Annual Meeting, showed meaningful anti-tumor activity across various cMET expression levels, histologies, and genetic alterations. MYTX-011 utilizes Mythic's FateControl™ technology, designed to improve tumor uptake and drug exposure. The KisMET-01 study is a first-in-human, open-label, multi-center trial evaluating MYTX-011 in patients with previously treated, locally advanced or metastatic NSCLC.
Key Highlights
- Positive efficacy data from Phase 1 KisMET-01 study of MYTX-011 in NSCLC presented at ASCO 2025.
- MYTX-011 demonstrated meaningful anti-tumor activity across different cMET expression levels, histologies, and genetic alterations.
- MYTX-011 leverages Mythic's innovative FateControl™ technology for improved safety, tolerability, and efficacy.
- Data represents the first disclosure of efficacy data for MYTX-011.
Incidence and Prevalence
Global Incidence and Prevalence of Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer deaths worldwide and the most common cause of cancer-related death. The majority of lung cancer cases are classified as non-small cell lung cancer (NSCLC), with estimates varying slightly between sources:
- 80-85% of lung cancer cases can be classified as NSCLC according to one source
- Another source indicates that 85% of all lung cancer cases reported are NSCLC
- One study states that NSCLC constitutes 70% of lung cancer cases
- Approximately 85% of all lung cancer incidences involve NSCLC
In terms of global incidence, NSCLC has a worldwide annual incidence of around 1.3 million cases.
Despite advancements in chemotherapy and targeted therapies, the 5-year survival rate has remained at 16% for the past forty years. The majority of patients are diagnosed with advanced disease and survival remains poor.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Non-small Cell Lung Cancer
Recent publications in PubMed highlight several key mechanisms of action (MoA) emerging for non-small cell lung cancer (NSCLC) treatment:
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors represent a key emerging MoA for NSCLC treatment with several important advantages:
- Anti-CTL4 and anti-PD1 antibodies are important immune checkpoint inhibitors used in NSCLC
- Pembrolizumab received accelerated approval for metastatic NSCLC whose tumors express programmed death-ligand 1 (PD-L1)
- PD-1 and PD-1 ligand inhibitors including nivolumab, MK3475, and MPDL3280 have demonstrated clinical efficacy in advanced/metastatic NSCLC
- These inhibitors are generally better tolerated and less toxic compared to conventional chemotherapy
Tyrosine Kinase Inhibitors (TKIs)
TKIs are specifically indicated for NSCLC adenocarcinoma positive for epidermal growth factor mutations:
- Three TKIs can be used as first-line treatment: gefitinib, erlotinib, and afatinib
- Osimertinib is administered when T790M mutation is diagnosed in disease relapse
Anti-angiogenesis Therapy
Targeting angiogenesis has emerged as an important approach:
- Ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor-2 (VEGFR-2), is used in combination with docetaxel
Taxanes
Taxanes work through a unique mechanism in NSCLC treatment:
- Paclitaxel and docetaxel promote assembly of microtubules and render them resistant to depolymerization
- Response rates of 21-24% for paclitaxel and 28-38% for docetaxel in advanced NSCLC
Recent Approvals for Early-Stage NSCLC
Several treatments have recently been approved for early-stage NSCLC:
- Adjuvant treatments: osimertinib, atezolizumab, and pembrolizumab
- Neoadjuvant therapy: nivolumab combined with chemotherapy
These emerging mechanisms of action represent significant advances in the treatment landscape for NSCLC, offering new options for patients with different disease characteristics and at various stages of treatment.
Study Design Parameters
Study Design Parameters and Endpoints in Key NSCLC Trials
EGFR Inhibitor Trials
- Twelve trials examining gefitinib compared to chemotherapy (n=6) or BSC (n=1), erlotinib compared to chemotherapy (n=3) or BSC (n=1), and gefitinib versus erlotinib (n=1)
- Patient populations categorized by EGFR mutation status: EGFR M+, EGFR M-, and EGFR unknown
- Data sources included EMBASE, MEDLINE, The Cochrane Library, PubMed
- Primary endpoints: overall survival (OS), progression-free survival (PFS)
Pembrolizumab Trials
- KEYNOTE-010: Phase II/III study comparing pembrolizumab (2 or 10 mg/kg) versus docetaxel in previously treated patients
- Randomization 1:1:1 with HRQoL measured using EORTC QLQ-C30, QLQ-LC13, and EuroQoL-5D
- 1,033 patients with PD-L1-expressing advanced NSCLC
- Treatment duration: up to 35 cycles/2 years
- After 42.6-month median follow-up: Pembrolizumab improved OS over docetaxel in PD-L1 TPS ≥50% (HR 0.53) and ≥1% groups (HR 0.69)
- Endpoints: OS, PFS, response rates, treatment-related adverse events
Neoadjuvant Pembrolizumab Trial
- Phase II study (NCT02818920) with primary endpoint of safety and secondary endpoints of efficacy
- Enrolled patients with untreated clinical stage IB to IIIA NSCLC
- Two cycles of pembrolizumab (200 mg) administered before surgery
Spanish Lung Cancer Group Trial (Elderly NSCLC)
- Single-arm, open-label, phase II clinical trial
- Conducted at ten sites in Spain (2018-2019)
- Included patients ≥70 years with stage IIIB or IV aNSCLC and PD-L1 expression ≥1%
- Treatment: 200 mg intravenous pembrolizumab every three weeks for maximum two years
- Primary endpoint: OS at one year
- Secondary endpoints: PFS, disease-specific survival, response rate, tolerability, quality of life changes, geriatric assessments
- Results: 83 patients recruited, estimated OS at one year was 61.7%, median OS was 19.2 months
Erlotinib Adjuvant Therapy Trial
- Open-label phase II trial for resected stage IA to IIIA EGFR-mutant NSCLC
- Patients received erlotinib 150 mg daily for 2 years after standard adjuvant chemotherapy
- Primary endpoint: 2-year disease-free survival (DFS)
- Powered to demonstrate 2-year DFS >85% (vs. historic data of 76%)
- Enrolled 100 patients across seven sites
PROFILE 1014 Trial (ALK-positive NSCLC)
- International multicenter phase III trial
- Compared crizotinib versus standard chemotherapy
- Established crizotinib as standard first-line therapy for advanced ALK-positive NSCLC
- Endpoints: Demonstrated superiority of crizotinib over standard chemotherapy
Anti-PD-1/L1 Agents Network Meta-analyses
- Evaluated nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab
- Nineteen randomized clinical trials (RCTs) involving 11,456 patients
- Analyzed OS, PFS, objective response rate, and adverse events
- Results presented according to treatment lines and PD-L1 status
Selpercatinib Trial (LIBRETTO-001)
- Global, open-label, phase I/II study in RET fusion-positive NSCLC
- Patients completed EORTC QLQ-C30 at baseline and throughout treatment
- Change of ≥10 points considered clinically meaningful
- 239 patients categorized by prior therapy: treatment-naïve (n=39), one prior line (n=64), two+ prior lines (n=136)
F-FDG PET Dynamic Modeling Study
- Clinical trial registration number: NCT03679936
- Included 62 NSCLC cases: 37 with early and locally advanced lung cancer without distant metastases and 25 with metastatic lung cancer
- Methodology: Dynamic F-FDG PET scans with Patlak graphic analysis and SUV analysis
- Endpoints: Imaging characteristics of primary tumor and metastatic lymph nodes
Drug used in other indications
Based on the provided context, there is no specific information available about MYTX-011 clinical trials for indications other than Non-small cell lung cancer. The context does not contain any references to MYTX-011, its clinical applications, or any intervention models for trials involving this particular treatment.
The context does mention various other cancer treatments and their intervention models, including:
- Cetuximab added to first-line chemotherapy for patients with high epidermal growth factor receptor (EGFR) expression
- Afatinib compared to chemotherapy for patients with EGFR-mutation-positive adenocarcinomas
- Crizotinib compared to second-line chemotherapy with docetaxel or pemetrexed for patients with advanced anaplastic lymphoma kinase-positive NSCLC
- Selumetinib added to docetaxel compared with docetaxel alone in patients with advanced KRAS-mutant NSCLC
- Nintedanib added to docetaxel in the second-line therapy of patients with advanced NSCLC
Additionally, the context mentions other treatments like ramucirumab, erlotinib, resveratrol, selpercatinib, vandetanib, and various EGFR tyrosine kinase inhibitors for different cancer indications.
However, none of these treatments are identified as MYTX-011, and no specific information about MYTX-011 trials or intervention models is provided in the context.