UT Health San Antonio Treats First Patient in Groundbreaking Solid Tumor Immunotherapy Trial

A Milestone in Cancer Research at UT Health San Antonio

In a significant advancement for cancer treatment innovation, the UT Health San Antonio Multispecialty and Research Hospital has successfully enrolled and treated its first clinical trial participant in a phase 2 study targeting advanced solid tumors. This event, announced in late March 2026, underscores the institution's pivotal role as an academic health center driving forward-thinking medical research. Affiliated with The University of Texas at San Antonio (UTSA), the hospital represents the culmination of efforts to integrate patient care, cutting-edge research, and medical education under one roof, providing South Texans with access to therapies typically available only at elite national facilities.

The trial focuses on invikafusp alfa, known as STAR0602, a pioneering immunotherapy developed by Marengo Therapeutics. Administered via intravenous infusion and combined with sacituzumab govitecan (SG), an established antibody-drug conjugate, this regimen aims to supercharge the patient's immune system against solid tumors—those non-blood-based cancers like breast, lung, and colorectal that have long resisted immunotherapy successes seen in blood cancers.

Unpacking the Novel Immunotherapy: STAR0602 and Its Mechanism

Invikafusp alfa (STAR0602) stands out as a first-in-class selective T-cell receptor-targeting bifunctional antibody-fusion protein. It functions as a dual agonist, mimicking OX40 ligand (OX40L) and interleukin-2 (IL-2) to selectively activate tumor-reactive T cells. Unlike traditional checkpoint inhibitors that broadly unleash the immune system, STAR0602 precisely targets T cells already primed against cancer, potentially minimizing off-target effects and cytokine storms that plague other therapies.

In preclinical models, STAR0602 demonstrated potent anti-tumor activity across antigen-rich solid tumors, particularly those with high tumor mutational burden (TMB-H). The phase 2 dose-expansion arm of the STARt-002 trial (NCT06067931) evaluates its safety, tolerability, and efficacy when paired with SG, which delivers a cytotoxic payload to TROP2-expressing cancer cells. Early data from Marengo's phase 1/2 studies showed promising single-agent responses in PD-1 refractory tumors, with objective response rates exceeding expectations in hard-to-treat settings.

The treatment protocol requires up to 72 hours of inpatient monitoring post-infusion to track immune activation, a capability made possible by the hospital's state-of-the-art design. This setup not only ensures patient safety but also generates real-time data to refine dosing and predict responses, accelerating the path from bench to bedside.

Mays Cancer Center: The Academic Powerhouse Behind the Trial

Central to this achievement is the Mays Cancer Center at UT Health San Antonio, the region's only National Cancer Institute (NCI)-designated Comprehensive Cancer Center. As part of UTSA's academic ecosystem, it bridges translational research with clinical application, boasting over 175 active trials and substantial funding from sources like the Cancer Prevention & Research Institute of Texas (CPRIT), which awarded $3 million in 2025 for South Texas-focused initiatives.

Recent accolades include $12.6 million for drug resistance studies, $1.6 million in Recruitment of Rising Stars (STARs) Awards, and V Foundation grants, fueling breakthroughs in genomics, immunotherapy, and disparities research. The center's emphasis on Latino health—given South Texas's demographics—aligns with NCI priorities, positioning UT Health San Antonio as a leader in equitable oncology advancements.

The new Multispecialty and Research Hospital, opened in December 2024, enhances this mission by enabling inpatient trials previously limited to outpatient settings. This integration fosters multidisciplinary collaboration among oncologists, immunologists, nurses, and pharmacologists, training the next generation of researchers through hands-on involvement.

Navigating Challenges in Solid Tumor Immunotherapy

While immunotherapies like CAR-T cells have revolutionized blood cancers—with response rates up to 80-90% in leukemias—solid tumors present formidable hurdles. The immunosuppressive tumor microenvironment (TME), characterized by exhausted T cells, regulatory T cells, and myeloid-derived suppressor cells, dampens immune attacks. Antigen heterogeneity leads to escape variants, and physical barriers like dense stroma hinder T-cell infiltration.

Statistics highlight the gap: only 10-20% of solid tumor patients respond to checkpoint inhibitors, compared to over 50% in melanomas. CAR-T trials in solids report median progression-free survival under 6 months, versus years in hematologic malignancies. Therapies like STAR0602 address these by selectively expanding tumor-specific T cells, bypassing broad activation risks.

• TME Suppression: Chronic antigen exposure causes T-cell exhaustion; bifunctional agonists like STAR0602 reinvigorate without overstimulating.
• Trafficking Issues: Chemokine mismatches prevent infiltration; combination with ADCs like SG may disrupt stroma.
• Antigen Loss: TMB-H tumors provide neoantigens, targeted via TCR engagement.

SG itself boasts robust efficacy, with TROPiCS-02 trial showing 5-month PFS in pretreated metastatic triple-negative breast cancer (mTNBC), setting a strong foundation for combos.

The Research Team Leading the Charge

Principal investigator Virginia Kaklamani, MD, DSc, leads Mays' breast cancer program. A prolific researcher with over 350 publications, her work spans targeted therapies and genetics linking obesity to breast cancer risk. Previously at Northwestern, she designs trials emphasizing biomarkers for personalized medicine.

Treating physician Jessica Treviño Jones, MD, an associate professor in hematology/oncology, highlights the patient-centered approach: spacious rooms allow family stays during monitoring, easing emotional burdens. Chief medical officer W. Allen Fink, DO, MHA, calls this a "defining milestone," operationalizing the hospital's healing-through-discovery ethos.

Executive director Lei Zheng, MD, PhD, notes expanded inpatient capabilities, while Therica Miller oversees research administration, ensuring bidirectional knowledge flow from labs to clinics.

Patient Impact and Trial Design Insights

For the inaugural participant with advanced solid tumors, this trial offers hope where standard options faltered. Requiring 72-hour observation, it balances innovation with safety, using multidisciplinary teams for holistic care. Broader enrollment targets TMB-H colorectal, breast, and other solids, building on phase 1 data showing tumor regressions.

Marengo's STARt-002 spans 25 sites globally, with UT Health SA as Texas's sole participant—a testament to its expertise. Endpoints include overall response rate, duration of response, and safety, with memory T-cell formation as a novel proxy for long-term efficacy.

South Texas Focus: Addressing Cancer Disparities

South Texas bears a heavy cancer burden, with higher incidences among Latinos. Mays Cancer Center's NCI designation amplifies efforts like the Advancing Cancer Research for Latinos conference (Feb 2026), fostering community trials and prevention. This trial exemplifies equitable access, bringing phase 2 innovation locally versus distant hubs.

Educational Ripple Effects in Higher Education

As UTSA's health arm, these trials enrich curricula. Medical students rotate through Mays, witnessing immunotherapy evolution firsthand. Residencies in oncology gain exposure to bifunctional agents, preparing graduates for academia-industry hybrids. Research funding sustains PhD programs, with CPRIT supporting rising stars in immuno-oncology.

Future Horizons: From Trial to Standard Care

Positive phase 2 data could propel STAR0602 toward approval, transforming solid tumor management. UT Health SA plans more inpatient trials, leveraging its infrastructure. Nationally, overcoming TME barriers promises broader immunotherapy wins, with bifunctionals like this heralding a new era.

For aspiring researchers, this exemplifies academic medicine's triad: discovery, delivery, dissemination—fueling careers in oncology at institutions like UTSA.

Photo by Annie Spratt on Unsplash