TROP2 ADC for Cancer (A264 Trial)
Recruiting in Palo Alto (17 mi)
+147 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Klus Pharma Inc.
No Placebo Group
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?A Phase I-II, First-in-Human Study of SKB264 in Patients with Locally Advanced Unresectable/Metastatic Solid Tumors who are refractory to Available Standard Therapies. Patient must have historically documented, incurable, locally advanced or metastatic cancer that are refractory to standard therapies of one of the following types:
1. Triple negative breast cancer
2. Epithelial ovarian cancer
3. Non-small cell lung cancer
4. Gastric adenocarcinoma/Gastroesophageal junction adenocarcinoma
5. Small cell lung cancer
6. HR+/ HER2-breast cancer
7. Head and neck squamous cell carcinoma
8. Endometrial carcinoma
9. Urothelial carcinoma
Will I have to stop taking my current medications?
The trial requires that you stop any standard cancer therapy or experimental therapy at least 4 weeks or five half-lives before starting the study drug. Additionally, you cannot use strong inhibitors or inducers of CYP3A4 at least 14 days prior to and throughout the study.
What makes the drug SKB264 (MK-2870) unique for cancer treatment?
SKB264 (MK-2870) is unique because it targets Trop-2, a protein overexpressed in many cancers, using an antibody-drug conjugate (ADC) approach. This allows it to deliver chemotherapy directly to cancer cells, potentially reducing side effects and improving effectiveness compared to traditional chemotherapy.
12345Eligibility Criteria
Adults aged 18-75 with advanced solid tumors that can't be surgically removed or have spread and don't respond to standard treatments. Specific cancers include certain types of breast, ovarian, lung, gastric, head and neck, endometrial, and urothelial cancers. Participants must have acceptable organ function and blood counts, not require oxygen for daily activities or have severe heart conditions.Inclusion Criteria
I am fully active or can carry out light work.
My kidneys work well enough to clear waste from my blood.
My cancer is advanced, cannot be cured, and started in the lining of organs.
I am between 18 and 75 years old.
Exclusion Criteria
I have been treated with TROP 2 targeted therapies before.
I have a serious heart condition that needs treatment.
I haven't had cancer treatment in the last 4 weeks or before the study drug's half-life period.
I need extra oxygen to do my daily activities.
I haven't had major surgery in the last 4 weeks.
I have high blood pressure or diabetes that is not well-managed.
I have severe eye conditions like dry eye, Meibomian gland disease, or macular degeneration.
I have fluid buildup in my chest causing symptoms.
I have moderate to severe numbness, tingling, or pain in my hands or feet.
I have had lung conditions that needed steroids or caused severe breathing problems.
I have or had liver disease, including hepatitis, alcoholism, or cirrhosis.
I need a procedure to remove excess fluid from my abdomen.
Participant Groups
SKB264 is being tested in this Phase I-II trial on patients with various advanced solid tumors unresponsive to standard therapies. The study aims to evaluate the safety and effectiveness of SKB264 as a potential treatment option for these patients.
11Treatment groups
Experimental Treatment
Group I: Phase II: Urothelial carcinomaExperimental Treatment1 Intervention
Histologically or cytologically documented, incurable, locally advanced or metastatic cancer
Group II: Phase II: Triple Negative Breast CancerExperimental Treatment1 Intervention
Histologically documented or cytologically , incurable, locally advanced or metastatic cancer
Group III: Phase II: Non-Small Cell Lung CancerExperimental Treatment1 Intervention
Histologically documented or cytologically, incurable, locally advanced or metastatic cancer
Group IV: Phase II: Head and Neck Squamous Cell CarcinomaExperimental Treatment1 Intervention
Histologically documented or cytologically, incurable, locally advanced or metastatic cancer
Group V: Phase II: HR+/ HER2- Breast CancerExperimental Treatment1 Intervention
Histologically documented or cytologically, incurable, locally advanced or metastatic cancer
Group VI: Phase II: Gastric Adenocarcinoma or Gastroesophageal Junction AdenocarcinomaExperimental Treatment1 Intervention
Histologically or cytologically documented, incurable, locally advanced or metastatic cancer
Group VII: Phase II: Extensive-stage Small Cell Lung CancerExperimental Treatment1 Intervention
Histologically documented or cytologically, incurable, locally advanced or metastatic cancer
Group VIII: Phase II: Epithelial Ovarian CancerExperimental Treatment1 Intervention
Histologically documented or cytologically, incurable, locally advanced or metastatic cancer
Group IX: Phase II: Endometrial carcinomaExperimental Treatment1 Intervention
Histologically documented or cytologically, incurable, locally advanced or metastatic cancer
Group X: Phase II: Cervical CancerExperimental Treatment1 Intervention
Histologically or cytologically documented, incurable, locally advanced or metastatic cancer
Group XI: Phase I: Dose EscalationExperimental Treatment1 Intervention
Five dose levels have been selected for evaluation in the Phase I part of the study: 2, 4, 6, 9, and 12 mg/kg of SKB264
SKB264 is already approved in China, European Union, United States for the following indications:
🇨🇳 Approved in China as SKB264 for:
- Triple-negative breast cancer
- EGFR-mutated non-small cell lung cancer
🇪🇺 Approved in European Union as SKB264 for:
- Clinical trials approved but no specific indications listed yet
🇺🇸 Approved in United States as SKB264 for:
- Clinical trials ongoing but no specific indications approved yet
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Los Angeles Hematology Oncology Medical GroupGlendale, CA
Florida Cancer Specialists & Research InstituteLake Mary, FL
BRCR Medical Center, IncPlantation, FL
Willis-Knighton Medical CenterShreveport, LA
More Trial Locations
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Who is running the clinical trial?
Klus Pharma Inc.Lead Sponsor
References
Targeting Trop-2 in solid tumors: future prospects. [2023]Trop-2 is a transmembrane glycoprotein that is upregulated in all cancer types independent of baseline levels of Trop-2 expression. Trop-2 is an ideal candidate for targeted therapeutics due to it being a transmembrane protein with an extracellular domain overexpressed on a wide variety of tumors as well as its upregulated expression relative to normal cells. As a result, several Trop-2-targeted therapeutics have recently been developed for clinical use, such as anti-Trop-2 antibodies and Trop-2-targeted antibody-drug conjugates (ADC). Subsequently, multiple early-phase clinical trials have demonstrated safety and clinical benefit of Trop-2-based ADCs across multiple tumor types. This includes clinical benefit and tolerability in tumor types with limited treatment options, such as triple-negative breast cancer, platinum-resistant urothelial cancer, and small-cell lung cancer. In this review, we elaborate on all clinical trials involving Trop-2.
Targeting Trop-2 in cancer: Recent research progress and clinical application. [2023]The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein involved in Ca2+ signaling in tumor cells. It is highly expressed in various tumor tissues than in normal tissues and represents a novel and promising molecular target for caner targeted therapy. Up to now, the mechanisms and functions associated with Trop-2 have been extensively studied in a variety of solid tumors. According to these findings, Trop-2 plays an important role in cell proliferation, apoptosis, cell adhesion, epithelial-mesenchymal transition, as well as tumorigenesis and tumor progression. In addition, Trop-2 related drugs are also being developed widely. There are a number of Trop-2 related ADC drugs that have demonstrated potent antitumor activity and are currently been studied, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd). In this study, we reviewed the progress of Trop-2 research in solid tumors. We also sorted out the composition and rationale of Trop-2 related drugs and summarized the related clinical trials. Finally, we discussed the current status of Trop-2 research and expanded our perspectives on its future research directions. Importantly, we found that Trop-2 targeted ADCs have great potential for combination with other antitumor therapies. Trop-2 targeted ADCs can reprogramme tumor microenvironment through multiple signaling pathways, ultimately activating antitumor immunity.
Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. [2022]Trop2 is a transmembrane glycoprotein encoded by the Tacstd2 gene. It is an intracellular calcium signal transducer that is differentially expressed in many cancers. It signals cells for self-renewal, proliferation, invasion, and survival. It has stem cell-like qualities. Trop2 is expressed in many normal tissues, though in contrast, it is overexpressed in many cancers and the overexpression of Trop2 is of prognostic significance. Several ligands have been proposed that interact with Trop2. Trop2 signals the cells via different pathways and it is transcriptionally regulated by a complex network of several transcription factors. Trop2 expression in cancer cells has been correlated with drug resistance. Several strategies target Trop2 on cancer cells that include antibodies, antibody fusion proteins, chemical inhibitors, nanoparticles, etc. The in vitro studies and pre-clinical studies, using these various therapeutic treatments, have resulted in significant inhibition of tumor cell growth both in vitro and in vivo in mice. A clinical study is underway using IMMU-132 (hrS7 linked to SN38) in patients with epithelial cancers. This review describes briefly the various characteristics of cancer cells overexpressing Trop2 and the potential application of Trop2 as both a prognostic biomarker and as a therapeutic target to reverse resistance.
[Expression and clinical significance of Trop-2 in human pancreatic cancer]. [2011]To investigate the expression and its clinical significance of Trop-2 in human pancreatic cancer.
Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer. [2023]Trop2 is a transmembrane glycoprotein and calcium signal transducer with limited expression in normal human tissues. It is consistently overexpressed in a variety of malignant tumors and participates in several oncogenic signaling pathways that lead to tumor development, invasion, and metastasis. As a result, Trop2 has become an attractive therapeutic target in cancer treatment. The anti-Trop2 antibody-drug conjugate (Trodelvy™, sacituzumab govitecan) has been approved to treat metastatic triple-negative breast cancer. However, it is still unclear whether the success observed in Trop2-positive breast cancer could be replicated in other tumor types, owing to the differences in the expression levels and functions of Trop2 across cancer types. In this review, we summarize the recent progress on the structures and functions of Trop2 and highlight the potential diagnostic and therapeutic value of Trop2 beyond breast cancer. In addition, the promising novel Trop2-targeted agents in the clinic were discussed, which will likely alter the therapeutic landscape of Trop2-positive tumors in the future.