Enhanced Cell Therapy Gets Fast Track Designation for HPV16+ Solid Tumors

SQZ Biotechnologies’ SQZ-eAPC-HPV, an investigational cell therapy intended to treat patients with HPV16+ advanced or metastatic solid tumors, has been granted fast track designation by the FDA.

SQZ-eAPC-HPV is based on the company’s second-generation Enhanced Antigen Presenting Cell (eAPC) platform. The platform "simultaneously delivers five different mRNAs—each encoding for a different protein which plays a part in stimulating key T-cell activation signals required to generate an immune response against tumors—to 4 different cell types." SQZ-eAPC-HPV is currently being investigated in the phase 1/2 COMMANDER-001 clinical trial (NCT05357898). Data from the trial presented at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress, being held December 7-9, 2022, in Geneva, Switzerland, included the observation of stable disease in 2 of 4 evaluable patients, with 1 patient having achieved a pronounced pharmacodynamic response with prolonged stable disease. In terms of safety, there were no dose-limiting toxicities (DLTs) experienced by the patients in cohort 1 during the 28-day DLT period, and no serious adverse events (AEs) related to treatment were reported. The company additionally stated that SQZ-eAPC-HPV is capable of being manufactured in less than 24 hours.

SQZ Biotechnologies previously presented data from a phase 1/2 clinical trial of SQZ-PBMC-HPV (NCT04084951), its APC cell therapy candidate for the same indication, at ESMO-IO 2021. SQZ-PBMC-HPV was granted fast track designation by the FDA in April of this year; however, the company expects to discontinue enrollment in the clinical trial by the end of 2022 in order to transition enrollment to COMMANDER-001.

“Receiving FDA Fast Track Designation underscores the significant potential of our SQZ eAPC candidate, which is designed to generate an even more powerful immune response than our APC candidate,” Marshelle Smith Warren, MD, chief medical officer, SQZ Biotechnologies, said in a statement regarding the news. “The initial safety and tolerability data presented at ESMO-IO today supports our recent portfolio prioritization decision to focus on our eAPC program. In addition to the clean safety profile, we were pleased to observe stable disease in 2 of the 4 evaluable patients in the eAPC trial. The team is working diligently to add more eAPC sites to our study to achieve our goal of a highest-dose monotherapy data readout by the middle of 2023.”

The 2-part, open-label, multicenter COMMANDER-001 study is expected to enroll approximately 60 patients aged 18 years or older with histologically confirmed incurable or metastatic HPV16+ solid tumors. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, at least 1 measurable lesion, a lesion that can be biopsied with acceptable clinical risk, and adequate organ function and bone marrow reserve within the 14 days before leukapheresis. Patients in the second part of the trial must additionally not have previously been treated with immune check-point inhibitors. Patients with active central nervous system metastases; those with grade 2 or higher AEs related to previous anticancer or investigational therapy that have not resolved at least 2 weeks prior to leukapheresis (excepting grade 2 neuropathy, ototoxicity, mucositis, fatigue, alopecia, or endocrine disorders managed with hormone replacement); and those with HIV infection, active hepatitis B or hepatitis C infection, or active mycobacterium tuberculosis infection will be excluded from the study. Additional exclusion criteria relate to patient health status, health history, and treatment history.

The trial is investigating SQZ-eAPC-HPV as both a monotherapy and as part of a combination therapy with pembrolizumab. The first part of the study will evaluate treatment-experienced patients in a dose-escalation scheme for the monotherapy approach and in a dose de-escalation scheme for the combination therapy approach. The trial’s second part will evaluate a combination therapy approach for patients who are treatment-naïve for immune checkpoint inhibitors. The study’s primary end points are the number of participants with treatment-emergent AEs and the number of participants who experience DLTs in the various treatment schemes. The study’s secondary end points include the objective response rate, best overall response, progression-free survival, duration of response, disease-control rate, overall survival, and the amount of investigational product from individual patient blood collection in terms of batch yield and number of product failures. The study is currently recruiting at locations in Arizona, Colorado, and Tennesse, and has an estimated completion date of March 24, 2024.

REFERENCE

SQZ Biotechnologies receives FDA fast track designation for its eAPC therapeutic candidate for treatment of HPV16+ tumors and presents clinical data for multiple programs at the European Society for Medical Oncology Immuno-Oncology Congress. News release. SQZ Biotechnologies Company. December 6, 2022. https://investors.sqzbiotech.com/news/news-details/2022/SQZ-Biotechnologies-Receives-FDA-Fast-Track-Designation-for-its-eAPC-Therapeutic-Candidate-for-Treatment-of-HPV16-Tumors-and-Presents-Clinical-Data-for-Multiple-Programs-at-the-European-Society-for-Medical-Oncology-Immuno-Oncology-Congress/default.aspx