Brenus Pharma Reports Promising Phase Ia Results for STC-1010 in Metastatic Colorectal Cancer, With 57% Objective Response Rate
Brenus Pharma, a clinical-stage biotechnology company developing innovative immunotherapies for cancer, has announced the first clinical results from the Phase Ia dose-escalation portion of its BreAK CRC-001 study evaluating STC-1010 in patients with metastatic colorectal cancer. The initial findings indicate a favorable safety profile, encouraging signs of clinical activity, and measurable changes in tumor-associated immune responses among patients with advanced disease.
The study enrolled nine patients with unresectable metastatic colorectal cancer, a population with significant treatment challenges and limited options for achieving long-term disease control. At baseline, 89% of enrolled patients had liver metastases, and 89% had KRAS-mutant tumors. These characteristics reflect a population in which conventional immunotherapy approaches have historically demonstrated limited effectiveness, particularly among patients whose tumors exhibit low immunogenicity.
At the time of the analysis, the median follow-up was eight months, with individual follow-up periods ranging from one to 14 months. The data cut-off was June 8, 2026. Among the seven patients evaluable for clinical activity under Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), the study reported a disease control rate of 100% and an objective response rate of 57%, corresponding to four patients achieving an objective response.
Additionally, three of the seven evaluable patients, or 43%, became eligible for surgery after treatment. Two of these patients subsequently had no evidence of disease. The preliminary results also showed substantial reductions in circulating tumor DNA (ctDNA), alongside changes in immune-cell infiltration and composition that support further investigation of STC-1010’s proposed mechanism of action.
According to Brenus Pharma, these findings provide an early indication that STC-1010 may help address important challenges associated with treating immunologically unresponsive colorectal tumors.
Addressing Immunotherapy Resistance in Colorectal Cancer
Colorectal cancer remains a significant oncology challenge, particularly when the disease has progressed to an unresectable or metastatic stage. Although immune checkpoint inhibitors have transformed treatment for several cancer types, their effectiveness in colorectal cancer depends substantially on the molecular and immunological characteristics of the tumor.
Approximately 95% of metastatic colorectal cancers are characterized by proficient mismatch repair (pMMR) and microsatellite stability (MSS). These tumors generally have fewer features that make them readily recognizable to the immune system and are often described as immunologically “cold” tumors.
Unlike tumors with deficient mismatch repair or high microsatellite instability, which can be more responsive to immune checkpoint inhibitors, pMMR/MSS colorectal cancers frequently demonstrate resistance to conventional immunotherapy. Their tumor microenvironment may restrict the recruitment, activation, or effective function of immune cells capable of recognizing and destroying cancer cells.
This resistance presents a major unmet medical need, particularly for patients with metastatic disease involving the liver or tumors carrying mutations such as KRAS. Developing treatments that can stimulate an effective antitumor immune response in these patients could expand future therapeutic options.
Brenus Pharma is developing STC-1010 as an in vivo dendritic cell engager designed to help make immunologically cold tumors more visible to the immune system. The company’s approach seeks to stimulate immune recognition and promote a coordinated response against cancer cells within the tumor microenvironment.
The initial results from BreAK CRC-001 are intended to evaluate whether this therapeutic strategy can produce measurable biological and clinical effects in patients with advanced colorectal cancer.
Phase Ia Study Design and Patient Characteristics
BreAK CRC-001 is an early-stage clinical study investigating STC-1010 through a dose-escalation approach. The Phase Ia portion is designed to evaluate the treatment’s safety and tolerability while generating initial information about its potential clinical activity and biological effects.
Nine patients with unresectable metastatic colorectal cancer were treated in the reported analysis. The patient population included individuals with disease characteristics associated with difficult-to-treat metastatic cancer.
Liver metastases were present in 89% of patients, while 89% had KRAS-mutant tumors. These features are clinically relevant because metastatic colorectal cancer involving the liver can be difficult to control, and KRAS mutations can influence treatment selection and therapeutic outcomes.
The median follow-up period was eight months, ranging from one to 14 months, with data collected through June 8, 2026. Clinical activity was assessed in seven evaluable patients using RECIST 1.1, a standardized framework for determining changes in tumor burden during cancer treatment.
Because the study remains in an early phase and the efficacy analysis includes only seven evaluable patients, the findings should be considered preliminary. Nevertheless, the reported response rates, surgical outcomes, molecular changes, and immune measurements provide several areas for further investigation.
Favorable Initial Safety and Tolerability Findings
Safety and tolerability are central objectives of the dose-escalation stage of an early-phase oncology trial. The initial findings from BreAK CRC-001 indicated that STC-1010 was well tolerated in the nine treated patients.
No dose-limiting toxicities were reported during the analysis. In addition, treatment-related adverse events were limited to Grade 1 or Grade 2 events, indicating that the reported related toxicities were mild to moderate in severity.
The absence of observed dose-limiting toxicity is an encouraging early finding because it supports continued evaluation of the treatment within the study’s dose-escalation framework. However, a small patient population cannot fully characterize the frequency of less common adverse events or establish the overall safety profile of an investigational therapy.
Further enrollment and longer follow-up will be important to determine whether this initial tolerability profile remains consistent as more patients receive treatment and investigators explore additional dose levels or treatment schedules.
Brenus Pharma said the safety findings support continued clinical investigation of STC-1010, while the accompanying clinical and biological signals provide a basis for further evaluating its therapeutic potential.
Clinical Activity: 100% Disease Control and 57% Objective Response Rate
The efficacy analysis included seven evaluable patients, all of whom achieved disease control according to the reported RECIST 1.1 assessment. This corresponded to a disease control rate of 100%.
Four of the seven evaluable patients achieved an objective response, producing an objective response rate of 57%. Objective responses generally include complete responses, in which no evidence of measurable disease remains under the assessment criteria, and partial responses, in which tumor burden decreases by a specified amount.
Disease control includes objective responses as well as stable disease, where the cancer does not meet the criteria for either sufficient tumor shrinkage or disease progression.
The reported response rate provides an initial signal of antitumor activity in a population characterized by advanced disease and a high prevalence of KRAS mutations. The disease control findings are also noteworthy because patients with pMMR/MSS colorectal cancer frequently experience limited benefit from conventional immunotherapy.
However, the results do not establish the comparative effectiveness of STC-1010 against existing treatment options. The study is an early-phase investigation, and its small evaluable population means that response estimates may change as additional patients are treated and followed.
Future analyses will need to establish the durability of responses, the extent of tumor reduction across different disease subgroups, and whether the early findings can be reproduced in a larger clinical population.
Conversion to Surgical Eligibility in Three Patients
One of the notable observations from the initial analysis was the change in surgical eligibility among patients whose disease had initially been considered unresectable.
Three of the seven evaluable patients, representing 43%, became eligible for surgery following treatment. Of these three patients, two had no evidence of disease afterward.
In metastatic colorectal cancer, surgery may be considered in selected patients when the distribution and extent of disease allow the removal of visible cancer. However, many patients with extensive metastatic involvement cannot undergo potentially curative surgery at diagnosis.
Treatment that reduces tumor burden or changes the distribution of disease may create an opportunity for surgical intervention in selected cases. This can be particularly relevant when metastases involve the liver, although the suitability of surgery depends on individual patient characteristics, disease location, response to treatment, and multidisciplinary clinical assessment.
The reported surgical conversions therefore represent a potentially meaningful finding. They suggest that treatment may have helped some patients reach a point at which surgery became feasible.
The observation must nevertheless be interpreted cautiously. Only seven patients were included in the evaluable efficacy population, and additional information about the surgical procedures, pathological findings, follow-up, and long-term outcomes will be needed to determine the durability and clinical significance of these results.
Even so, the possibility of converting initially unresectable disease into a surgically manageable situation is an important area for further research in metastatic colorectal cancer.
Molecular Findings Show Substantial Reductions in Circulating Tumor DNA
The study also examined circulating tumor DNA as a potential indicator of treatment-associated changes in cancer burden.
ctDNA consists of small fragments of DNA released into the bloodstream by tumor cells. Measuring these fragments can help investigators monitor molecular changes during treatment and assess whether cancer-associated genetic signals are increasing or decreasing.
In the reported analysis, ctDNA levels declined by as much as 97% within two months of treatment. The company also reported that TP53 and KRAS mutations became nearly undetectable in the circulating molecular measurements.
These findings provide a biological signal that may be consistent with a reduction in detectable tumor-derived material in the bloodstream. The observations are particularly relevant in a study population in which KRAS-mutant disease was common.
However, a reduction in ctDNA does not by itself establish complete tumor eradication or guarantee long-term disease control. Molecular measurements must be interpreted alongside radiographic assessments, clinical outcomes, and subsequent follow-up.
Additional research will be needed to determine how consistently ctDNA changes correlate with objective responses, surgical outcomes, and longer-term disease control in patients receiving STC-1010.
Immune Profiling Indicates Changes Within the Tumor Microenvironment
Beyond clinical and molecular outcomes, Brenus Pharma reported immune-profiling findings from the first six patients treated in the study. These analyses were intended to examine whether STC-1010 could influence the immune-cell populations associated with tumor recognition and destruction.
The reported results showed that the STC-1010 regimen was associated with a 285% increase in cytotoxic CD8-positive T-cell infiltration within tumors at the second assessment time point compared with baseline. This corresponds to nearly a fourfold level relative to the initial measurement.
Cytotoxic CD8-positive T cells play an important role in antitumor immunity because they can recognize and destroy cancer cells displaying relevant antigens. Increasing their presence within a tumor may indicate that the tumor microenvironment has become more accessible to immune-mediated attack.
The analysis also showed a 2.5-fold increase in the CD4-positive T-cell-to-regulatory T-cell ratio, with a reported p-value below 0.05.
Regulatory T cells, commonly known as Tregs, help control immune activity and maintain immune tolerance. Although this function is important under normal physiological conditions, regulatory T cells within tumors can suppress antitumor immune responses. A higher CD4-positive T-cell-to-Treg ratio may therefore reflect a shift in the local immune environment, although the clinical meaning depends on the specific cell populations and their functional characteristics.
Investigators also observed an increase in circulating T cells. The company said this finding was consistent with the possibility that immune cells were moving toward the tumor. However, additional analyses would be required to establish the mechanisms responsible for these changes and determine whether they directly contribute to clinical responses.
In a presented patient case, immune profiling identified antigen-presenting macrophages within the tumor. These cells can contribute to immune regulation and antigen presentation, potentially helping other immune cells recognize tumor-associated targets.
The analysis also showed a shift in peripheral T cells toward a memory phenotype and expansion of tumor-reactive PD-1-positive, CD39-positive T cells. Memory T cells can support sustained immune responses, while the PD-1 and CD39 markers can help researchers characterize T-cell populations associated with chronic antigen exposure and tumor reactivity.
Taken together, these observations suggest that treatment was associated with measurable changes in the immune environment in the small group evaluated. Further studies will be required to determine how these changes relate to the proposed mechanism of STC-1010 and whether they can predict treatment benefit across a broader patient population.
Company and Investigator Perspectives
Paul Bravetti, Chief Executive Officer of Brenus Pharma, said the first clinical findings support the company’s initial safety assessment and provide early evidence of potential efficacy.
“These data validate STC-1010’s safety. They reinforce our hypotheses with early efficacy signals and the potential to improve the therapeutic landscape of cold tumor,” Bravetti said.
His comments highlight the company’s objective of developing an approach that could address the limited responsiveness of immunologically cold tumors to existing immunotherapy strategies.
Prof. François Ghiringhelli of Centre Georges-François Leclerc in Dijon, the study’s principal investigator, emphasized the importance of the surgical outcomes observed in the study.
“Making initially unresectable patients eligible for surgery is what matters most in first-line metastatic colorectal cancer. Seeing it alongside immune activation in MSS tumors is a remarkable signal for patients,” Ghiringhelli said.
The comments underscore two important aspects of the preliminary findings: the potential to alter treatment possibilities for selected patients and the evidence of immune activation in a cancer type that has historically been difficult to treat with immunotherapy.
Next Steps for STC-1010 Development
The Phase Ia findings provide an initial assessment of STC-1010’s safety, clinical activity, molecular effects, and immunological impact in metastatic colorectal cancer. The combination of disease control, objective responses, conversion to surgical eligibility, ctDNA reductions, and changes in immune-cell populations offers several directions for continued investigation.
The next stages of clinical development will need to establish whether these early observations are reproducible in larger patient groups and whether treatment-associated changes translate into durable clinical benefits. Longer follow-up will also be important for assessing progression-free survival, overall survival, the durability of objective responses, and outcomes following surgery.
Further research will need to clarify which patients are most likely to benefit, how treatment response relates to tumor characteristics, and whether the observed immune changes can serve as biomarkers of activity.
For patients with pMMR/MSS metastatic colorectal cancer, the need for additional therapeutic approaches remains substantial. Brenus Pharma’s STC-1010 program is seeking to address this unmet need by promoting immune recognition and activity within tumors that are typically resistant to conventional immunotherapy.
While the initial results are promising, the small study population and early stage of development mean that definitive conclusions about efficacy and long-term benefit cannot yet be drawn. Continued clinical evaluation will determine whether the signals observed in BreAK CRC-001 can support the further development of STC-1010 as a potential treatment option for patients with advanced colorectal cancer.
About BreAK CRC-001 (NCT06934538) is an international, open-label Phase I/II trial in unresectable locally advanced or metastatic pMMR/MSS, BRAF wild-type CRC. STC-1010 is administrated with oral low-dose cyclophosphamide per os ± GM-CSF, in frontline combined with chemotherapy.