CureVac N.V. (Nasdaq: CVAC) announced today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for CVHNLC, paving the way for Phase 1 clinical trials in patients with squamous non-small cell lung cancer (sqNSCLC). This regulatory milestone marks a significant advancement for the company's oncology pipeline and its mRNA-based precision immunotherapy approach.
CVHNLC represents a novel approach to cancer immunotherapy, consisting of two different mRNA constructs that encode eight tumor-associated antigens (TAAs) prevalent across sqNSCLC patients. Notably, the therapy includes a novel class of TAAs that have not been previously tested in cancer immunotherapy trials.
Novel Therapeutic Design and Mechanism
CVHNLC has been developed using CureVac's advanced second-generation mRNA backbone. The therapy features two different constructs utilizing unmodified mRNA formulated in lipid nanoparticles (LNPs). Its multi-epitope design includes four well-established antigens with proven relevance in solid tumors, alongside four novel antigens uniquely identified through CureVac's proprietary whole-genome discovery platform.
Dr. Myriam Mendila, CureVac's Chief Scientific Officer, explained the rationale behind the approach: "Squamous non-small cell lung cancer exhibits a high prevalence of shared tumor antigens among patients, presenting a unique opportunity for developing targeted off-the-shelf mRNA immunotherapies. We believe by administering CVHNLC with checkpoint inhibition, we will trigger an amplified and targeted immune response, thereby increasing the efficacy against the cancer."
Phase 1 Trial Design
The upcoming Phase 1 study will be a dose-finding, open-label trial assessing the safety and tolerability of CVHNLC in combination with pembrolizumab in patients with advanced sqNSCLC. The study is structured in two parts:
-
Part A (Dose Escalation): First-line maintenance treatment after either chemotherapy combined with pembrolizumab or pembrolizumab monotherapy. Patients with metastatic Stage IV sqNSCLC who have received at least three cycles of pembrolizumab will be enrolled. CVHNLC doses will range between 100μg and 400μg, administered with pembrolizumab maintenance therapy for up to 12 months or until disease progression or undue toxicity occurs.
-
Part B (Optional Dose Expansion): CVHNLC will be tested in combination with first-line chemotherapy and pembrolizumab.
Primary endpoints include the incidence of dose-limiting toxicities and treatment-related adverse events. Secondary endpoints encompass overall response rate, progression-free survival, duration of response, and disease control rate. Patient treatment is anticipated to begin in the second half of 2025.
Addressing an Urgent Medical Need
Squamous non-small cell lung cancer represents approximately 20-30% of all NSCLC cases, which account for 87% of the approximately 225,000 new lung cancer cases diagnosed annually in the U.S. According to the American Cancer Society. SqNSCLC is considered a more aggressive form of lung cancer with poorer prognosis compared to other NSCLC types.
"Immune checkpoint blockade has become a new standard of care for patients with metastatic squamous non-small cell lung cancer; however, overall prognosis still remains poor in advanced as well as in early settings of this disease, highlighting the urgent need for new therapeutic options," noted Dr. Mendila.
The disease is characterized by a 30-40% relapse rate within two years in early settings after neoadjuvant treatment, with median overall survival of only 15-17 months in metastatic settings.
Strategic Significance for CureVac's Oncology Pipeline
CVHNLC represents CureVac's second oncology program to enter clinical development, highlighting the company's growing focus on cancer immunotherapy applications for its mRNA technology platform.
"CVHNLC is our second oncology program to enter the clinical stage, highlighting the continued progress we are making with our mRNA-based precision immunotherapies," said Dr. Alexander Zehnder, Chief Executive Officer of CureVac. "Importantly, we have been able to design CVHNLC using both known, shared tumor antigens and novel proprietary antigens discovered using our differentiated in-house technology platform."
The company is leveraging this approach in the design of multiple novel cancer mRNA programs in collaboration with MD Anderson Cancer Center, with additional candidates anticipated to enter clinical trials in the next 18-24 months.
About CureVac
Founded in 2000, CureVac (Nasdaq: CVAC) is a pioneering multinational biotech company focused on developing transformative medicines based on messenger RNA (mRNA) technology. With more than two decades of experience in mRNA development, the company has refined key technologies that were essential to the production of mRNA vaccines against COVID-19.
CureVac is now applying its expertise to new therapeutic areas with significant unmet medical needs, particularly in oncology. The company is leveraging mRNA technology alongside advanced omics and computational tools to design both off-the-shelf and personalized cancer immunotherapy product candidates. CureVac also maintains programs in prophylactic vaccines and treatments enabling the human body to produce its own therapeutic proteins.
Headquartered in Tübingen, Germany, CureVac operates additional sites in the Netherlands, Belgium, Switzerland, and the United States.
