On November 7, 2025 Researchers from Rutgers Cancer Institute, New Jersey’s only National Cancer Institute (NCI) – designated Comprehensive Cancer Center, and RWJBarnabas Health, along with colleagues from the National Cancer Institute, a center of the National Institutes of Health, reported findings from two HPV-related studies that highlight the potential of novel T cell therapies to achieve long-lasting remission and complete tumor regression in patients with advanced epithelial cancers. Christian Hinrichs, MD, Co-Director of the Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence at Rutgers Cancer Institute and Chief of the Section of Cancer Immunotherapy, led the studies and presented these findings at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, in National Harbor, Maryland, November 5–9, 2025.

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In one study, researchers reported encouraging interim results from a Phase II clinical trial evaluating genetically engineered T cell receptor (TCR)-T cells designed to target the HPV16 E7 oncoprotein (E7 T cells) in patients with metastatic HPV-associated cancers. The treatment consisted of a conditioning regimen, a single infusion of up to 50 billion E7 T cells, and a median of three doses of adjuvant aldesleukin. All 10 patients had advanced cancers that are generally regarded as incurable and for which there are limited treatment options. Five had head and neck cancer, two had cervical cancer, two had anal cancer, and one had esophageal cancer. The treatment was generally well tolerated, with side effects consistent with the preparative regimen and aldesleukin. Six out of 10 patients achieved substantial tumor shrinkage, including two patients who experienced complete tumor regression that remains ongoing at 11 and 12 months, respectively. Both of these patients had previously received immunotherapy and other standard therapeutic options.

"Metastatic HPV-associated cancers remain difficult to treat," said Dr. Hinrichs. "We found that E7-directed T cells can induce meaningful, and sometimes complete, responses in patients with limited options. It’s an encouraging step toward effective engineered T cell therapies for these and other epithelial cancers."

Development of this treatment has been through a collaboration between the National Cancer Institute and Rutgers Cancer Institute, with the phase II study conducted at Rutgers Cancer Institute. The cell products for the study were manufactured in a Good Manufacturing Practices (GMP) facility on-site at Rutgers Cancer Institute, a part of the Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence. The Center is uniquely positioned to advance the development of novel cell therapies through its specialized research capabilities and GMP infrastructure, supporting both innovative clinical trials and the translation of laboratory discoveries into patient care.

"When I finished my treatment, I couldn’t believe how quickly I started feeling better," said Maria, a patient from Philadelphia. "Within a month, the nodules were gone, and for the first time in years, I felt free, full of energy and living the life. I can spend time with my son, do the things I love, and really enjoy life again. I’m so grateful to the team that made this possible and proud to be living proof of the difference their research can make."

In a second study, investigators reported the extraordinary finding that two patients with metastatic cervical cancer remain in complete remission 10 years after receiving a single infusion of tumor-infiltrating lymphocyte (TIL) therapy. Conducted as part of clinical trial NCT01585428, the study represents the strongest evidence-to-date that cellular therapy can produce long-term, potentially curative responses in epithelial cancers, the most common type of malignancy. A decade after treatment, patients exhibited no evidence of disease based on imaging and circulating tumor DNA analysis. Administered anti-tumor T cells underwent a temporary expansion phase that coincided with tumor shrinkage and apparent elimination. Tumor responses have continued long after the T cell responses suggesting that the tumors were cleared during the initial response.

"Findings like these highlight the importance of conducting research at an NCI-designated Comprehensive Cancer Center such as Rutgers Cancer Institute," said Steven K. Libutti, MD, FACS, William N. Hait Director, Rutgers Cancer Institute and Senior Vice President, Oncology Services, RWJBarnabas Health. "Centers like ours, the only one in New Jersey, bring together the scientific expertise, clinical resources and collaborative environment needed to translate new discoveries from the laboratory into clinical trials, and ultimately into meaningful treatments for patients."

One patient who has had an ongoing complete response is Sue of Washington, DC. "Participating in this clinical trial felt like a calling. When I joined the study, my cancer was very advanced, and I wanted to use whatever time I had left to help enhance research that could benefit others. I never imagined the treatment would work for me, but just two months after receiving my TIL infusion, my cancer was undetectable on the scans," said Sue. "Now, 12 years later, I’m still cancer-free and deeply grateful to the doctors and researchers who made that possible. It’s an incredible and unexpected blessing to see how my participation has led to new discoveries that have the potential to help other patients in the future."

"These studies indicate that one-time cell therapies can achieve durable responses in epithelial cancers, which historically have been more resistant to these treatments than blood cancers," said Dr. Hinrichs. "The decade-long complete responses to TIL therapy give hope that these patients may be cured. The E7 T cell results that include complete responses are encouraging and support continued study of the approach."

(Press release, Rutgers Cancer Institute of New Jersey, NOV 7, 2025, View Source [SID1234659647])

On November 7, 2025 Halozyme Therapeutics, Inc. (NASDAQ: HALO) (Halozyme) reported that Johnson & Johnson received U.S. Food and Drug Administration (FDA) approval of a new indication for DARZALEX Faspro (daratumumab and hyaluronidase-fihj) co-formulated with ENHANZE, as single agent treatment of adult patients with high-risk smoldering multiple myeloma (HR-SMM). DARZALEX Faspro is the first and only approved treatment for HR-SMM, enabling earlier intervention before the disease progresses to active multiple myeloma.

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"DARZALEX Faspro is the first approved treatment in the U.S. for adult patients with high risk smoldering multiple myeloma," said Dr. Helen Torley, President and CEO of Halozyme. "The approval expands the indications for DARZALEX Faspro with ENHANZE, further solidifying its role as a cornerstone therapy across all stages of multiple myeloma."

Smoldering multiple myeloma (SMM) is an asymptomatic malignancy that is genomically the same as active multiple myeloma and where these abnormal cells can be detected in the bone marrow.1,2,3 In 2025, it is estimated that more than 36,000 people will be diagnosed with multiple myeloma in the U.S., and approximately 15 percent of those are classified as smoldering.4,5 An estimated 50 percent of patients diagnosed with HR-SMM are likely to progress to active disease within two years of diagnosis.5 Currently, the standard of care for HR-SMM is active monitoring to track signs of biochemical progression and/or end-organ damage. Recent evidence suggests that people at high-risk of progressing to active multiple myeloma could benefit from earlier therapeutic intervention.5

The FDA approval is based on findings from the AQUILA study (NCT03301220), which evaluated the efficacy and safety of DARZALEX Faspro compared to active monitoring (or "Watch and Wait") in the largest Phase 3 trial in patients with HR-SMM. For more information on the study and its findings, please view Johnson & Johnson’s press release issued on November 6, 2025.

(Press release, Halozyme, NOV 7, 2025, View Source [SID1234659645])

On November 7, 2025 Gilead Sciences, Inc. (Nasdaq: GILD) reported the Phase 3 ASCENT-07 study investigating Trodelvy (sacituzumab govitecan-hziy) versus chemotherapy as a first-line treatment post-endocrine therapy in HR+/HER2-negative metastatic breast cancer patients did not meet the primary endpoint of progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1 criteria.

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Overall survival is a key secondary endpoint and was not mature at the time of the primary analysis; however, an early trend was observed favoring patients treated with Trodelvy compared to chemotherapy. The ASCENT-07 study will continue to further assess overall survival.

"HR+/HER2-negative metastatic breast cancer is a highly heterogeneous disease, and this complexity makes it particularly challenging to manage, especially in patients whose disease has already progressed on multiple lines of endocrine therapy," said Hope S. Rugo, MD, ASCENT-07 Principal Investigator, Chief, Division of Breast Oncology, Director of Women’s Cancer Program, City of Hope Comprehensive Cancer Center. "It will be critical that we continue to follow patients for overall survival to better understand the potential impact of sacituzumab govitecan long-term in this treatment setting."

The safety profile was consistent with prior Trodelvy breast cancer studies and no new safety signals were identified in this patient population.

"Trodelvy remains a standard of care for pre-treated HR+/HER2-negative metastatic breast cancer based on the demonstrated overall survival results seen in the TROPiCS-02 study," said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. "We are deeply grateful to the patients, their families, advocates, and investigators who continue to contribute to this important research. We look forward to sharing the full data of ASCENT-07 at an upcoming medical conference."

Trodelvy is the only globally approved Trop-2-directed antibody-drug conjugate (ADC) to show meaningful overall survival advantages in two distinct types of metastatic breast cancer: pre-treated HR+/HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) metastatic breast cancer and second-line and later metastatic triple-negative breast cancer (TNBC). Trodelvy is recognized as a Category 1 preferred treatment for both approved indications per the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelinesi) and is the only ADC with a European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) rating of 5 for metastatic TNBC and a rating of 4 for HR+/HER2-negative mBC.

Trodelvy also stands as the only ADC to demonstrate a statistically significant and clinically meaningful PFS improvement in the first-line metastatic TNBC setting regardless of PD-L1 status across two positive Phase 3 studies (ASCENT-04 and ASCENT-03) presented earlier this year.

Gilead continues to build on this foundation with a robust development program exploring Trodelvy across multiple disease stages and tumor types, including the ongoing Phase 3 ASCENT-05 study in high-risk early-stage TNBC (eTNBC) and additional Phase 3 studies evaluating its potential in lung and gynecologic cancers.

The use of Trodelvy in patients as a first treatment post-endocrine therapy in HR+/HER2-negative metastatic breast cancer is investigational, and its safety and efficacy have not been established in this population. The use of Trodelvy in first-line metastatic TNBC is also investigational and the safety and efficacy have not been established for that use.

About HR+/HER2-negative Metastatic Breast Cancer (First Treatment Post-Endocrine Therapy)
HR+/HER2-negative is the most common breast cancer subtype, representing ~70% of cases (~400,000 diagnoses globally each year). While endocrine therapies have extended survival, nearly all patients with metastatic disease eventually progress and become resistant. Once patients are no longer candidates for endocrine therapy, chemotherapy becomes the primary treatment option but is often linked to higher rates of disease resistance and limited clinical outcomes. Attrition between treatment lines is substantial, underscoring the need for more effective and better-tolerated options earlier in care, regardless of IHC status (IHC 0, 1+, 2+/ISH-).

About the ASCENT-07 Study
The ASCENT-07 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of Trodelvy (sacituzumab govitecan-hziy) compared with treatment of physician’s choice chemotherapy in patients with locally advanced, inoperable, or HR+/HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) metastatic breast cancer who have received prior endocrine therapy and are candidates for cytotoxic chemotherapy. The study enrolled 654 patients across nearly 30 countries.

Patients were randomized 2:1 to receive either sacituzumab govitecan-hziy (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) or treatment of physician’s choice, which included a choice of single-agent chemotherapy including capecitabine, paclitaxel and nab-paclitaxel. Treatment continued until BICR-verified disease progression or unacceptable toxicity.

The primary endpoint of the study is PFS as assessed by BICR according to RECIST v1.1 criteria. Key secondary endpoints include overall survival, objective response rate, quality of life, and safety.

More information about ASCENT-07 is available at ClinicalTrials.gov: NCT05840211.

About Trodelvy
Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2-negative metastatic breast cancer. With more than 60,000 cancer patients treated globally over the past five years, healthcare professionals have extensive real-world experience with Trodelvy, which has shown generally consistent outcomes across clinical and real-world settings.

Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2-negative breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.

INDICATIONS

TRODELVY (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: NEUTROPENIA AND DIARRHEA

TRODELVY can cause severe, life-threatening, or fatal neutropenia. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Primary prophylaxis with G-CSF is recommended for all patients at increased risk of febrile neutropenia. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
TRODELVY can cause severe diarrhea. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to TRODELVY.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur as early as the first cycle of treatment and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 of USPI.

Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions.

Nausea and Vomiting: TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

ADVERSE REACTIONS

In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY.

Please see full Prescribing Information, including BOXED WARNING.

(Press release, Gilead Sciences, NOV 7, 2025, View Source [SID1234659644])

On November 7, 2025 Phio Pharmaceuticals Corp. (NASDAQ: PHIO) a clinical-stage siRNA biopharmaceutical company developing therapeutics using its proprietary INTASYL gene silencing technology to eliminate cancer, reported that it will present clinical data from its ongoing Phase 1b clinical trial at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), which will be held in National Harbor, Maryland from November 7-9, 2025.

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Phio’s poster presentation will highlight the clinical results from the ongoing Phase 1b dose escalation clinical trial. This clinical trial is designed to evaluate the safety and tolerability of intratumoral injection of PH-762 in patients with cutaneous squamous carcinoma, Merkel cell carcinoma, and melanoma.

Presentation Details are as follows:

Title: PD-1 Directed Intratumoral Immunotherapy for Cutaneous Carcinomas: A Clinical Study of INTASYL PH-762
Abstract Number: 610
Presenting Author: Mary Spellman, M.D.
Date: Saturday November 8, 2025
Location: Prince George ABC Exhibit Halls Gaylord National Resort and Convention Center

(Press release, Phio Pharmaceuticals, NOV 7, 2025, View Source [SID1234659643])

On November 7, 2025 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported new data from its ongoing Phase 2 clinical trial evaluating vilastobart, a tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab (Tecentriq) in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). A 40% objective response rate (ORR) was demonstrated in heavily pre-treated patients with MSS mCRC without liver metastases and with high plasma TMB (≥10 mutations/Mb), as well as a statistically significant correlation between plasma TMB status and response. These new clinical data are being presented in a late-breaking poster presentation (Abstract # 1315) today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 40th Annual Meeting, taking place from November 5-9, 2025, in National Harbor, Maryland.

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"These compelling new Phase 2 data for vilastobart in combination with atezolizumab demonstrated a 40% objective response rate in heavily pre-pretreated patients with MSS mCRC without liver metastases and with high plasma TMB, signifying an important advance in our understanding of response to novel immunotherapy in MSS mCRC," said Katarina Luptakova, M.D., chief medical officer of Xilio. "In addition, these data showed a statistically significant correlation between plasma-based TMB and response. We estimate that approximately 55% of patients with MSS CRC have high plasma TMB, representing a meaningful patient population who could ultimately benefit from combination treatment with vilastobart and a substantially greater prevalence of patients with high TMB than previously estimated using traditional tissue-based assays."

"These new data highlight the potential to use plasma TMB as a predictive biomarker and identify patients with MSS mCRC who may benefit from treatment with vilastobart, a tumor-activated anti-CTLA-4, in combination with a PD-(L)1," said Diwakar Davar, M.D., Associate Professor of Medicine, Clinical Director of the Melanoma Program and Medical Oncologist/Hematologist at the UPMC Hillman Cancer Center. "This biomarker guided approach, utilizing a feasible and reproducible biomarker, together with vilastobart’s differentiated safety profile, continue to support the promising opportunity for vilastobart in combination with PD-(L)1 or PD1-VEGF in MSS mCRC, as well as other tumor types."

Promising Opportunity for Plasma-Based TMB as a Biomarker Predictive of Response to Combination Treatment with Vilastobart in Patients with MSS mCRC

Tissue-based TMB has demonstrated potential as a biomarker predictive of response to immune checkpoint inhibitors in many tumor types. However, tissue-based TMB assays have not shown predictive utility in MSS mCRC historically, and these tissue-based assays may underestimate the mutational burden in patients. In particular, tissue-based assays are limited to evaluating mutations in a single-site biopsy specimen, which is typically taken once at the time of diagnosis, and cannot account for tumor heterogeneity or changes in TMB over time.

Newer plasma-based assays show potential to better assess TMB status and be used as a biomarker predictive of response in patients with MSS mCRC. These plasma-based assays are more sensitive than traditional tissue-based assays in that plasma-based TMB assays provide a comprehensive assessment of mutational load and account for tumor heterogeneity. In addition, plasma can be readily obtained from blood samples throughout the course of treatment, accounting for changes in TMB over time without the need for invasive procedures.

Approximately 55% of non-MSI-H CRC patients were plasma TMB high (>10 mutations/Mb) based on an analysis of the GuardantINFORM real-world clinical-genomic database in approximately 8,000 patients who received the Guardant360 Liquid (Infinity) assay and who had non-MSI-H disease and a reportable TMB result. In contrast, historical data for tissue-based TMB assays have suggested <10% of patients with MSS mCRC were TMB-high.

These data support the meaningful opportunity to use plasma-based TMB as a biomarker predictive of response to combination treatment with vilastobart in patients with MSS mCRC.

New Data from Phase 2 Trial for Vilastobart in Combination with Atezolizumab in Patients with MSS mCRC Without Liver Metastases and with High Plasma TMB

As of a data cutoff date of May 12, 2025, 44 patients with MSS mCRC had been treated with the combination of vilastobart at 100 mg once every six weeks (Q6W) and atezolizumab at 1200 mg once every three weeks (Q3W), including 27 patients without liver metastases. Patients were heavily pre-treated, with 80% having previously received three or more prior lines of anti-cancer therapy.

In a retrospective analysis, 24 patients without liver metastases were evaluable for plasma TMB status. Baseline plasma TMB was assessed using the Guardant360 Liquid (Infinity) assay, and patients with TMB ≥10 mutations/Mb were defined as having high plasma TMB.

Clinical Efficacy Data

40% ORR in patients with MSS mCRC without liver metastases and high plasma TMB, with statistically significant correlation (p=0.05) between plasma TMB status and response.

•
40% ORR in plasma TMB-high patients, consisting of six partial responses (PRs), with five confirmed PRs (with one confirmed after the data cutoff date) and one unconfirmed PR.

•
In patients evaluable for plasma TMB status, 62.5% were TMB-high. All responders who were evaluable for plasma TMB status were TMB-high, and the correlation between plasma TMB status and response was statistically significant (p=0.05).

•
As previously reported, responses were deep and durable, with reductions in target lesions of up to 71% from baseline.

Safety Data

Vilastobart in combination with atezolizumab continued to demonstrate a differentiated and generally well-tolerated safety profile. Treatment-related adverse events (AEs) were primarily Grade 1 or 2, consistent with the tumor-activated design for vilastobart.

As previously reported, across all patients treated as of a data cutoff date of May 12, 2025 (n=44), the combination of vilastobart at 100 mg Q6W and atezolizumab at 1200 mg Q3W was generally well-tolerated. Treatment-related AEs were primarily Grade 1 or 2. Only two patients (5%) discontinued treatment for the combination of vilastobart and atezolizumab due to a treatment-related AE, and only three patients (7%) experienced colitis of any grade.

Clinical Development Plans for Vilastobart

Based on the promising clinical activity and safety profile demonstrated by vilastobart as a combination therapy, including in patients who had high plasma TMB, Xilio is actively seeking a partner to develop vilastobart in combination with PD-(L)1 or PD1-VEGF in MSS CRC and other tumor types.

Investor Conference Call Information

Xilio will host a conference call and webcast on Monday, November 10, 2025, at 4:30 p.m. ET. The webcast will feature a discussion with expert clinicians Aparna Parikh, M.D., Associate Professor of Medicine, Harvard Medical School, Program Director, GI Medical Oncology, Colorectal, Anal, and Neuroendocrine, Director of the MGB Global Cancer Care Program, Mass General Brigham Cancer Institute, Boston, MA, and Diwakar Davar, M.D., Associate Professor of Medicine, Clinical Director of the Melanoma Program and Medical Oncologist/Hematologist at the UPMC Hillman Cancer Center, Pittsburgh, PA. During the webcast, Xilio will discuss the new Phase 2 combination data for vilastobart and the promising opportunity to use high plasma TMB as a predictive biomarker for response, as well as briefly highlight additional data updates presented at SITC (Free SITC Whitepaper) across the company’s portfolio of differentiated masked immunotherapies.

Viewers can access the webcast by using this link. Listeners are encouraged to join at least 15 minutes prior to the scheduled start time. The webcast will also be accessible under "Events & Presentations" in the "Investors & Media" section of the Xilio Therapeutics website at ir.xiliotx.com. A replay of the webcast will be archived on the website for 30 days following the presentation.

About Vilastobart and the Phase 1/2 Combination Clinical Trial

Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME). In 2023, Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate vilastobart in combination with atezolizumab (Tecentriq) in a multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety of the combination in Phase 1C dose escalation in patients with advanced solid tumors and the efficacy and safety of the combination in Phase 2 in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with and without liver metastases. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

(Press release, Xilio Therapeutics, NOV 7, 2025, View Source [SID1234659642])