DC50292A tablets for MTAP-deleted advanced or metastatic solid tumors

An Open-Label Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of DC50292A Tablet in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors

This trial tests whether daily DC50292A tablets are safe, reach useful blood levels, and may help adults with advanced or metastatic solid tumors that lack MTAP.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Heronova Pharmaceuticals (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 8 sites (Fuzhou, Fujian and 7 other locations)
• Trial ID: NCT07071090 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, non-randomized, open-label study using a dose-escalation (accelerated 3+3) design followed by dose expansion to measure safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of DC50292A tablets in patients with MTAP-deficient advanced or metastatic solid tumors. Planned escalation cohorts span several dose levels with initial single-dose PK sampling, a 21-day daily dosing period with a 3-day break for DLT assessment in Cycle 1, and continuous dosing in subsequent cycles adjusted by safety and PK/PD findings. Patients with documented MTAP homozygous deletion or loss of MTAP protein and at least one measurable lesion who have exhausted standard therapies are eligible to continue treatment until progression or other protocol-specified discontinuation criteria. Study procedures require serial blood sampling, possible fresh biopsy or archived tissue for MTAP testing, and regular clinic visits at one of the participating centers in China.

Who should consider this trial

Good fit: Adults (≥18) with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors that are MTAP-deficient, with at least one measurable lesion and prior standard treatment failure, who can consent and comply with study visits are ideal candidates.

Not a fit: Patients whose tumors are not MTAP-deficient, who cannot provide tissue for testing or consent, or who have poor organ function or performance status that precludes trial participation are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, DC50292A could provide a new targeted oral treatment option for patients with MTAP-deleted tumors who have progressed on standard therapies.

How similar studies have performed: Targeting vulnerabilities in MTAP-deleted tumors is an emerging strategy with early-phase clinical activity reported for related agents, but it remains experimental and not yet broadly validated.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily signs the informed consent form, demonstrates understanding of the study, and is willing and able to comply with all trial procedures.
2. Age ≥18 years, regardless of gender.
3. Patients with histologically and/or cytologically confirmed solid tumors who are assessed by the investigator as having locally advanced, recurrent, or metastatic disease and have failed standard treatments at the current stage.
4. At least one measurable lesion as per RECIST v1.1 criteria, assessed via imaging (tumor lesions located in previously irradiated areas or those having undergone other local-regional therapies are generally not considered measurable unless clear progression is confirmed by the investigator).
5. MTAP deficiency, defined by one of the following: willingness to provide sufficient archived tumor tissue or fresh biopsy samples for MTAP testing; or documentation of MTAP homozygous deletion via NGS/IHC or loss of MTAP protein expression in tissue; or availability of a prior NGS report (within 3 years) confirming MTAP homozygous deletion or an IHC report confirming loss of MTAP expression, as accepted by the investigator.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Life expectancy ≥3 months.
8. Absence of severe hematological, hepatic, renal, coagulation, or cardiac dysfunction.
9. Male and female participants of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 3 months after the last dose of the study drug. Female participants of childbearing potential must have a negative serum pregnancy test result prior to the first dose of the study medication.

Exclusion Criteria:

1. Received chemotherapy, radiotherapy, biologics, endocrine therapy, immunotherapy, or other antitumor treatments within 4 weeks or 5 half-lives (whichever is shorter) before the first dose of the study drug, including: nitrosoureas or mitomycin C within 6 weeks prior; oral fluoropyrimidines or small-molecule targeted agents within 2 weeks or 5 half-lives (whichever is shorter); Chinese herbal medicines with antitumor indications within 2 weeks prior.
2. Received any non-marketed investigational drugs or therapies within 4 weeks prior to the first dose.
3. Undergone major organ surgery (excluding needle biopsy or surgery for pathologic fractures), significant trauma, or planned elective surgery during the trial within 4 weeks prior.
4. Used CYP3A4-sensitive substrates, strong inhibitors/inducers, CYP2C8-sensitive substrates, or P-gp inhibitors (see Appendix 3) within 14 days or 5 half-lives (whichever is shorter) prior.
5. Previously treated with PRMT5 or MAT2A inhibitors.
6. QTc interval ≥480 ms (mean of 3 measurements) on screening/baseline 12-lead ECG.
7. Prior allogeneic hematopoietic stem cell/bone marrow transplantation or solid organ transplantation, or current use of immunosuppressants/anti-rejection drugs.
8. Known allergy to any active/inactive ingredient of the study drug.
9. Adverse reactions from prior antitumor therapy not resolved to CTCAE v5.0 Grade ≤1 (except non-risks like alopecia, Grade 2 peripheral neuropathy, or stable hypothyroidism on hormone replacement).
10. Hepatitis B (HBsAg+ with HBV-DNA ≥2500 copies/mL or 500 IU/mL), HCV (HCV-RNA \> lower limit of detection), HIV-positive, or syphilis (both specific/non-specific antibodies positive).
11. Symptomatic/active CNS metastases, leptomeningeal disease, or spinal cord compression. Asymptomatic CNS metastases may enroll if:

    1. Measurable extracranial lesions per RECIST v1.1;
    2. No new/progressive CNS lesions for ≥4 weeks with stable neurologic symptoms;
    3. No seizures/increased intracranial pressure;
    4. No steroids/antiepileptics/dehydrants for ≥2 weeks.
12. Clinically significant third-space fluid accumulation (e.g., massive ascites/pleural effusion).
13. Cardiovascular Disease: severe arrhythmias (e.g., ventricular arrhythmias requiring intervention, AV block II-III); ACS, CHF, aortic dissection, stroke, or Grade ≥3 cardiovascular events within 6 months; NYHA Class ≥II or high-risk structural heart disease; uncontrolled hypertension (SBP ≥150 mmHg and/or DBP ≥95 mmHg); QTc prolongation risks (e.g., heart failure, uncorrected hypokalemia, congenital/family history of long QT syndrome, concomitant QT-prolonging drugs).
14. Systemic treatment for active infection within 4 weeks prior.
15. Acute esophageal/GI diseases affecting drug absorption (e.g., bowel obstruction, Crohn's disease, ulcerative colitis, short bowel syndrome).
16. Pulmonary Disease: interstitial lung disease (ILD), pulmonary fibrosis, or drug-induced pneumonitis requiring treatment.
17. Other Severe Conditions: hepatic, renal, neurologic/psychiatric, endocrine, hematologic, or immune disorders compromising study participation.
18. Other malignancies within 5 years (except cured malignancies like basal/ squamous cell skin cancer, low-risk prostate cancer, papillary thyroid cancer, or excised in situ cancers).
19. Known alcohol/drug dependence.
20. Psychiatric disorders or poor adherence.
21. Pregnant or breastfeeding women.
22. Investigator's Discretion: any other clinical/laboratory abnormalities deemed unsuitable for the study.

Where this trial is running

Fuzhou, Fujian and 7 other locations

• Fujian Cancer Hospital — Fuzhou, Fujian, China (Recruiting)
• Sun Yat-Sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Guangxi Medical University Cancer Hospital — Nanning, Guangxi, China (Recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• Shandong Cancer Hospital — Jinan, Shandong, China (Recruiting)
• Sir Run Run Shaw Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Kang Ren

Conditions Solid Tumor Malignancies