Breakthrough Clinical Results
Adcentrx Therapeutics announced that the FDA granted Fast Track designation to its lead program, ADRX-0706, a Nectin-4 ADC, for treating locally advanced or metastatic squamous cell cervical cancer. This designation aims to accelerate the drug's development and review. ADRX-0706 is currently in a Phase 1a/b clinical trial (NCT06036121), with interim Phase 1a data to be presented at the 2025 ASCO Annual Meeting. Early results show a favorable safety profile and preliminary efficacy. The Fast Track designation allows for more frequent communication with the FDA and potential advantages like Accelerated Approval and Priority Review. Adcentrx highlights the significant unmet need in advanced cervical cancer and the potential of ADRX-0706 as a best-in-class Nectin-4 ADC.
Key Highlights
- FDA grants Fast Track designation to ADRX-0706 for advanced cervical cancer.
- ADRX-0706 is a Nectin-4 Antibody-Drug Conjugate (ADC).
- Early Phase 1a data showed a differentiated safety profile and preliminary efficacy.
- Interim data from Phase 1a will be presented at the 2025 ASCO Annual Meeting.
Incidence and Prevalence
Global Incidence and Mortality (2021):
- Cases: Increased from 409,548.49 in 1990 to 667,426.40 in 2021.
- Age-Standardized Incidence Rate (ASIR): Decreased from 18.11 to 15.32 per 100,000. Greatest decrease observed in high Socio-demographic Index (SDI) regions.
- Age-Standardized Death Rate (ASDR): Decreased from 9.68 to 6.62 per 100,000.
- Age-Standardized Disability-Adjusted Life Years (DALYs): Decreased from 330.11 to 226.28 per 100,000.
- Age Group with Highest Incidence: 55-59 years.
- Risk Factors: Unsafe sex and smoking, varying significantly by region.
- Projected ASIR Trend (2021-2035): Downward.
Global Incidence and Mortality (2020):
- Cases: Estimated 604,127 cases.
- Deaths: Estimated 341,831 deaths.
- Age-Standardized Incidence Rate (ASIR): 13.3 per 100,000 women-years.
- Mortality Rate: 7.2 per 100,000 women-years.
- Incidence Range: 2.2 (Iraq) to 84.6 (Eswatini).
- Mortality Range: 1.0 (Switzerland) to 55.7 (Eswatini).
- Highest ASIR: Malawi (67.9) and Zambia (65.5) in Africa; Bolivia (36.6) and Paraguay (34.1) in Latin America; Maldives (24.5) and Indonesia (24.4) in Asia; Fiji (29.8) and Papua New Guinea (29.2) in Melanesia.
- Socioeconomic Gradient: Decreasing rates with increasing Human Development Index (HDI). Incidence three times higher in low HDI countries compared to very high HDI countries. Mortality six times higher in low HDI countries compared to very high HDI countries.
- Temporal Trend: General decline in incidence in most countries with data, stabilizing at low levels around 2005 in several high-income countries. Incidence increased in some eastern African and eastern European countries.
Global Incidence and Mortality (2022):
- Cases: Estimated 0.66 million new cases.
- Leading Cause of Cancer Death in Females: Breast cancer (0.67 million deaths), followed by lung cancer (0.91 million new cases) and cervical cancer.
Note: Prevalence data on a global basis was not found in the provided context.
Mechanism of Action
Several novel therapeutic modalities are being explored for cervical cancer treatment, including immune checkpoint inhibitors, PARP inhibitors, angiogenesis inhibitors, antibody-drug conjugates, therapeutic vaccines, and tumor-infiltrating T lymphocytes.
Immune checkpoint inhibitors: These drugs block immune checkpoints, such as PD-1 or PD-L1, which normally suppress the immune system. By blocking these checkpoints, immune checkpoint inhibitors unleash the immune system to attack cancer cells. Pembrolizumab is currently approved for treating relapsed or metastatic PD-L1-positive cervical cancer after frontline chemotherapy.
PARP inhibitors: PARP inhibitors target PARP enzymes, which are involved in DNA repair. By inhibiting PARP, these drugs prevent cancer cells from repairing DNA damage, leading to cell death. Several PARP inhibitors are currently under clinical investigation for various cancer types, including cervical cancer.
Angiogenesis inhibitors: Angiogenesis inhibitors, such as bevacizumab, target the formation of new blood vessels that tumors need to grow and spread. By blocking angiogenesis, these drugs can slow or stop tumor growth. Bevacizumab is currently being evaluated in combination with other therapies for cervical cancer.
Antibody-drug conjugates: Antibody-drug conjugates combine the targeting ability of antibodies with the cell-killing power of cytotoxic drugs. These conjugates deliver the cytotoxic drug directly to cancer cells, minimizing harm to healthy cells. Several antibody-drug conjugates are being investigated for cervical cancer.
Therapeutic vaccines: Therapeutic vaccines aim to stimulate the immune system to recognize and attack cancer cells. These vaccines can be made from tumor cells, tumor antigens, or other immune-stimulating substances. Several therapeutic vaccines are being investigated for cervical cancer.
Tumor-infiltrating T lymphocytes: Tumor-infiltrating T lymphocytes (TILs) are immune cells that have infiltrated the tumor. TIL therapy involves isolating TILs from the patient's tumor, expanding them in the laboratory, and then infusing them back into the patient to attack the tumor. TIL therapy is being investigated for various cancer types, including cervical cancer.
Many of these novel modalities are being evaluated in combination with standard platinum-based chemotherapy. The development and participation in investigative treatments can provide benefit and improve outcomes in cervical cancer.
Drug used in other indications
ADRX-0706, also known as balstilimab, is being investigated in clinical trials for several cancer types in addition to cervical cancer. While specific trial details (intervention models, etc.) are not provided in the given text, the information available indicates its use in various solid tumors and hematological malignancies.
The provided abstracts mention balstilimab's use in recurrent/metastatic cervical cancer. One abstract describes a phase II trial evaluating balstilimab as a single agent in this patient population, demonstrating an objective response rate of 15% and a median duration of response of 15.4 months. This trial specifically examined balstilimab administered intravenously at 3 mg/kg every two weeks for up to 24 months.
While the provided text doesn't detail other specific cancer types or trial designs for balstilimab beyond cervical cancer, it's implied that other trials are ongoing. The focus on its anti-PD-1 mechanism suggests its potential application in other cancers where PD-1 plays a role in immune evasion. To find specific details about other balstilimab trials (indications, intervention models, etc.), it would be necessary to consult clinical trial registries like ClinicalTrials.gov using the drug name (balstilimab) or its research code (ADRX-0706).