SOT102 for Gastric and Pancreatic Adenocarcinoma

(CLAUDIO-01 Trial)

No longer recruiting at 8 trial locations

Overseen By Richard Kapsa

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: SOTIO Biotech a.s.

Must not be taking: Corticosteroids, Anticonvulsants

Disqualifiers: Pulmonary fibrosis, CNS malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 28

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SOT102 for individuals with advanced or metastatic pancreatic cancer. Researchers aim to evaluate the effectiveness of SOT102 both alone and in combination with standard cancer treatments. The study seeks to determine the optimal dose of SOT102 and assess its effectiveness. Individuals with advanced pancreatic cancer who have exhausted other treatment options may be suitable candidates for this trial. As a Phase 1/Phase 2 trial, the study focuses on understanding how SOT102 works in participants and measuring its effectiveness in an initial, smaller group, providing participants early access to a potentially beneficial new treatment.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on corticosteroids or anticonvulsants for central nervous system metastases, you may not be eligible. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that SOT102 is likely to be safe for humans?

Research shows that SOT102 is a new treatment being tested for safety and effectiveness. Although detailed human safety data is not yet available, lab and animal studies have demonstrated that SOT102 has strong effects against tumors, suggesting it might help fight cancer cells.

This trial is in its early stages (Phases 1 and 2), focusing on finding the safest dose and observing how people respond. Early trials aim to identify any side effects and determine if the treatment is well-tolerated. If SOT102 were unsafe, it would not have reached this stage. So far, detailed reports of negative effects are absent, but researchers are closely monitoring participants for any issues.

In summary, while detailed human data remains limited, early lab study results are promising. Participants in this trial will help gather important safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for gastric and pancreatic adenocarcinoma, which typically involve chemotherapy and targeted therapies, SOT102 introduces a novel approach with its unique mechanism of action. SOT102 is administered as an intravenous infusion and is designed to work as a monotherapy or in combination with standard treatments. Its unique feature lies in its potential to target cancer cells more precisely, minimizing damage to healthy cells and potentially reducing side effects. Researchers are excited about SOT102 because it uses a modified Fibonacci scheme to escalate doses, which might help find the most effective dose more quickly and safely.

What evidence suggests that SOT102 might be an effective treatment for pancreatic adenocarcinoma?

Research has shown that SOT102, which participants in this trial will receive, is a promising new treatment for certain cancers. SOT102 targets a protein called Claudin 18.2, found in some tumors. Early lab and animal studies demonstrated that SOT102 can effectively fight tumors with this protein. This suggests it might work on gastric and pancreatic adenocarcinomas, which are difficult-to-treat cancers. While more research is needed to confirm these results in humans, the early findings are encouraging. ^{1 2 3 4 6}

Who Is on the Research Team?

Josep Tabernero, MD, PhD

Principal Investigator

Vall d'Hebron University Hospital (HUVH)

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic gastric or pancreatic adenocarcinoma. They must have tried at least two prior therapies (one for pancreatic cancer), not be pregnant, and agree to contraception. Excluded are those with severe preexisting conditions, recent major surgery, certain lung diseases, active infections, HIV/hepatitis B/C, or specific genetic deficiencies.

Inclusion Criteria

Your disease can be measured or not according to a certain set of guidelines.

You must have already tried at least two different treatments for your advanced or metastatic disease. If you have HER2 overexpression, you must have already tried anti-HER2 therapy for stomach cancer.

You have a disease that has spread and cannot be treated with surgery.

Exclusion Criteria

Severe preexisting medical conditions as per judgement of the investigator (e.g., active gastric or GEJ ulcer with or without bleeding, complete or incomplete gastric outlet syndrome with persistent or repetitive bleeding)

Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention

You have had lung problems like interstitial pneumonitis or pulmonary fibrosis in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

First-in-human, single-agent phase 1 trial of SOT102 in advanced/metastatic pancreatic cancer patients

28 days

Every 14 days

Combination Treatment (Part B)

Phase 1b dose escalation of SOT102 in combination with nab-paclitaxel/gemcitabine for first-line treatment

28 days

Every 14 days

Expansion (Part C)

Single-agent SOT102 expansion at RP2D identified in Part A in pancreatic cancer after prior therapies

Long-term

Combination Expansion (Part D)

SOT102 in combination with nab-paclitaxel/gemcitabine for first-line treatment expansion at RP2D identified in Part B

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SOT102

Trial Overview The trial tests SOT102 alone (Part A) and combined with standard chemotherapy (nab-paclitaxel/gemcitabine; Part B). It aims to find the maximum tolerated dose and recommended phase 2 dose of SOT102 as well as its effectiveness both alone (Part C) and in combination therapy (Part D).

How Is the Trial Designed?

Group I: SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg Experimental Treatment 1 Intervention

Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.,32 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. Upon completion of the SOT102 infusion, first-line SoC treatment was administered. SoC treatment was nab-paclitaxel (125 mg/m2) given as a 30- to 40-minute infusion followed by gemcitabine (1000 mg/m2) given as a 30-minute infusion on days 1, 8, and 15. This treatment was repeated every 28 days.

Group II: SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg Experimental Treatment 1 Intervention

Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.214 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.

Group III: SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg Experimental Treatment 1 Intervention

Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.128 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.

Group IV: SOT102 as Monotherapy (Part A) DL2 0.064 mg/kg Experimental Treatment 1 Intervention

Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.064 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.

Group V: SOT102 as Monotherapy (Part A) DL1 0.032 mg/kg Experimental Treatment 1 Intervention

Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.032 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.

Who Is Running the Clinical Trial?

SOTIO Biotech a.s.

Lead Sponsor

Trials

3

Recruited

270+

SOTIO Biotech

Lead Sponsor

Trials

2

Recruited

150+

Sotio Biotech Inc.

Lead Sponsor

Trials

2

Recruited

150+

Published Research Related to This Trial

In a study of 184 gastric adenocarcinoma patients, HER2 overexpression was linked to better survival rates in 10% of cases, while cMet overexpression was associated with worse survival in 4% of cases, highlighting the importance of these markers in prognosis.

FGFR2 amplification was found in 2% of cases and correlated with poorer survival, suggesting that targeting these receptor tyrosine kinase pathways could be beneficial for specific patient subpopulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGFR2, HER2 and cMet in gastric adenocarcinoma: detection, prognostic significance and assessment of downstream pathway activation. Betts, G., Valentine, H., Pritchard, S., et al.[2021]

COMMD10 expression is significantly elevated in gastric adenocarcinoma (STAD) tissues compared to normal tissues, and higher levels of COMMD10 are associated with poorer overall survival and worse clinical outcomes for STAD patients.

The study suggests that COMMD10 may influence STAD prognosis through mechanisms related to m6A RNA modifications and immune cell infiltration, particularly involving macrophages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of COMMD10 as a novel prognostic biomarker for gastric cancer. Zhao, W., Lin, J., Cheng, S., et al.[2023]

The study identified 114 differentially expressed genes (DEGs) in stomach adenocarcinoma (STAD) tissues compared to normal tissues, with 35 genes upregulated and 79 downregulated, highlighting potential targets for therapy.

Ten core genes (including COL1A1, FN1, and THBS2) were found to be significantly overexpressed in STAD tissues, suggesting they could serve as important prognostic biomarkers and therapeutic targets for future STAD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Potential Core Genes Associated With the Progression of Stomach Adenocarcinoma Using Bioinformatic Analysis. Yang, B., Zhang, M., Luo, T.[2022]

HOXC10 is significantly overexpressed in gastric cancer tissues compared to normal tissues, and its increased levels are linked to poorer recurrence-free survival in patients, suggesting it could serve as a prognostic marker.

The study found that HOXC10 promotes cell proliferation and metastasis in gastric cancer cell lines, and it directly regulates the expression of the CST1 gene, indicating its potential as a therapeutic target in gastric cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HOXC10 overexpression promotes cell proliferation and migration in gastric cancer. Kim, J., Bae, DH., Kim, JH., et al.[2020]

In a study of 178 gastric adenocarcinoma samples, high expression of FGF10 was significantly linked to worse outcomes, including lymph node invasion and distant metastasis, making it an independent unfavorable prognostic factor.

Knocking down FGF10 in gastric cancer cells reduced their migration, indicating that FGF10 not only serves as a poor prognostic biomarker but also promotes cancer cell invasion, suggesting it could be a promising target for new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of Fibroblast Growth Factor 10 Is Correlated with Poor Prognosis in Gastric Adenocarcinoma. Sun, Q., Lin, P., Zhang, J., et al.[2017]

The chimeric compound BIM-23A758 showed significant antitumor effects in human midgut carcinoid cells (GOT1), inducing apoptosis and inhibiting key signaling pathways, while having minor effects on other NET cell lines.

BIM-23A758's effectiveness is linked to high expression levels of somatostatin receptors (SSTR2) and dopamine type 2 receptors (D2R) in GOT1 cells, suggesting that targeting these receptors could be a promising strategy for treating neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The novel somatostatin receptor 2/dopamine type 2 receptor chimeric compound BIM-23A758 decreases the viability of human GOT1 midgut carcinoid cells. Zitzmann, K., Andersen, S., Vlotides, G., et al.[2021]

The combination of the gastrin antagonist Z-360 with gemcitabine was found to be safe and well tolerated in a study involving 33 patients with advanced pancreatic cancer, with common side effects including nausea and fatigue.

At the end of the study, 62.5% of patients receiving 120 mg of Z-360 and 25% receiving 240 mg had stable disease, suggesting potential benefits in disease management, although further Phase III trials are needed to confirm its efficacy compared to gemcitabine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib/IIa trial to evaluate the CCK2 receptor antagonist Z-360 in combination with gemcitabine in patients with advanced pancreatic cancer. Meyer, T., Caplin, ME., Palmer, DH., et al.[2022]

The study demonstrated that intratumoral injection of the SSTR2 gene significantly reduced tumor size and weight in pancreatic cancer xenografts in mice, indicating its potential efficacy as a treatment.

Restoring SSTR2 gene expression increased the apoptosis index in tumors, suggesting that this gene therapy approach could effectively induce cancer cell death in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene transfer of somatostatin receptor type 2 by intratumoral injection inhibits established pancreatic carcinoma xenografts. Du, ZY., Qin, RY., Xia, W., et al.[2019]

Among 397 patients treated for gastric adenocarcinoma from 1999 to 2009, long-term survival rates improved significantly, with 5-year survival increasing from 38.7% in the first half of the decade to 49.2% in the latter half.

In-hospital mortality for patients who underwent curative resection decreased from 8.5% to 2.0%, and there was a notable shift towards using primary stents instead of exploratory surgeries or bypass procedures for non-curative cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes among patients treated for gastric adenocarcinoma during the last decade. Bringeland, EA., Wasmuth, HH., Johnsen, G., et al.[2022]

The study identified three prognostic genes (AOX1, NNMT, and PTGIS) related to NAD+ metabolism in stomach adenocarcinoma (STAD), which could help stratify patients for personalized treatment options.

Survival analysis revealed significant differences between two patient clusters based on the expression of 27 differentially expressed NAD+ metabolism-related genes, indicating that these clusters may respond differently to treatments, including sensitivity to CTLA4 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of nicotinamide adenine dinucleotide (NAD+) metabolic genes in patients with stomach adenocarcinoma based on bioinformatics analysis. Cai, L., Ke, C., Lin, Z., et al.[2023]

Novel antibodies targeting CETN1 have been successfully developed, showing specific binding to pancreatic ductal adenocarcinoma (PDAC) tissues while sparing normal pancreatic tissue, indicating their potential for diagnostic use.

Radioimmunotherapy (RIT) using 213 Bi-labeled CETN1 antibodies demonstrated effective and safe treatment in mice with PDAC, suggesting a promising therapeutic approach for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of novel highly specific antibodies to cancer testis antigen Centrin-1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer. Jiao, R., Allen, KJH., Malo, ME., et al.[2021]

Overexpression of HOXD10 in pancreatic cancer cells significantly reduced their proliferation and invasive capabilities, indicating its role as a tumor suppressor.

In animal models, tumors with high HOXD10 levels were smaller and showed decreased markers associated with cancer progression, such as Ki67 and VEGF, suggesting that HOXD10 inhibits tumor growth and the epithelial-mesenchymal transition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of overexpression of the HOXD10 gene on the malignant proliferation, invasion, and tumor formation of pancreatic cancer cell PANC-1. Lin, Z., Hu, Y., Lin, R., et al.[2022]

In a study of 28 resected pancreatic ductal carcinoma samples, SMAD4 levels were found to increase in tumors compared to normal pancreatic tissue, but decreased in poorly differentiated tumors, suggesting its potential role in tumor progression.

The study also highlighted that higher expressions of TGFβR2, vimentin, and CD105 in tumor areas may be linked to the epithelial-to-mesenchymal transition, which could influence patient outcomes in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SMAD4 and TGFβR2 expression in pancreatic ductal carcinoma. Văduva, IA., Mărgăritescu, C., Georgescu, CV., et al.[2020]

The SSTR5 P335L SNP is prevalent in pancreatic cancer patients and varies by race, with significant implications for understanding its role in cancer biology and treatment response.

Overexpression of the SSTR5 L335 variant leads to increased cell proliferation and blocks the inhibitory effects of somatostatin analogs, suggesting it may negatively impact treatment efficacy in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The hypofunctional effect of P335L single nucleotide polymorphism on SSTR5 function. Zhou, G., Gingras, MC., Liu, SH., et al.[2022]

Novel drug conjugates designed with somatostatin-derived cyclic peptides effectively target pancreatic cancer cells by utilizing somatostatin receptors (SSTRs) that are commonly expressed in these cells.

The drug conjugates, which included Camptothecin, Combretastatin-4A, and Azatoxin, showed significant toxicity to pancreatic cancer cell lines and demonstrated targeted accumulation in tumors in animal models, indicating potential for effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New somatostatin-drug conjugates for effective targeting pancreatic cancer. Ragozin, E., Hesin, A., Bazylevich, A., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05525286

NCT05525286 | Clinical Trial of SOT102 Antibody Drug ... This trial will assess the MTD and RP2D of SOT102 administered as monotherapy (Part A) and in combination with first-line SoC treatment (nab-paclitaxel/ ...

2. esmoopen.com esmoopen.com/article/S2059-7029(23)00418-0/pdf

2P SOT102, a novel CLDN18.2-targeting antibody-drug ... Conclusions: SOT102 represents a novel potent ADC with the potential to treat. Claudin 18.2 expressing tumors irrespective of the intensity of expression. The ...

3. sotio.com sotio.com/news-publications/news/sotio-announces-first-patients-dosed-in-two-combination-arms-of-claudio-01-study-evaluating-sot102-in-first-line-gastric-and-pancreatic-cancer

SOTIO Announces First Patients Dosed in Two ... Preclinical data from studies of SOT102 have demonstrated potent anti-tumor efficacy in vitro and in vivo. SOT102 is currently being studied for ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-sot102-for-patients-with-advanced-gastric-and-pancreatic-cancer-alone-or-with-drug-combination/

Study on SOT102 for Patients with Advanced Gastric and ... The purpose of the study is to find out how safe and effective SOT102 is for patients with advanced stages of these cancers.

5. withpower.com withpower.com/trial/phase-2-adenocarcinoma-2-2022-530a7

SOT102 for Gastric and Pancreatic Adenocarcinoma In a study of 184 gastric adenocarcinoma patients, HER2 overexpression was linked to better survival rates in 10% of cases, while cMet overexpression was ...

6. clinicaltrials.eu clinicaltrials.eu/inn/sot102/

Sot102 – Application in Therapy and Current Clinical ... This clinical trial aims to evaluate the safety and effectiveness of SOT102 when used alone or in combination with standard care treatments. The study focuses ...