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.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Cardiac disease, Brain metastases, Liver disease, others

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. ^{1 2 3 4 5}

Research Team

Jordi Rodon Ahnert, MD, PhD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility 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

Patients must be able to provide documented voluntary informed consent

Your white blood cell count, platelet count, and hemoglobin levels are within a certain range.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't taken any experimental drugs within the last 4 weeks.

The investigator considers other situations that patients are not appropriate to participate in this trial

I have been treated with TROP 2 targeted therapies before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Dose Escalation

Participants receive SKB264 as a single IV infusion at escalating dose levels to determine the maximum tolerated dose (MTD) and recommended doses for expansion (RDEs).

12 months

Every 2 weeks in 4-week cycles

Phase II: Treatment

Participants receive SKB264 at the recommended dose levels for expansion to evaluate the objective response rate (ORR) and other efficacy measures.

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and overall survival.

4 weeks

Treatment Details

Interventions

• SKB264 (Antibody-drug conjugate)

Trial Overview 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.

Participant Groups

Group I: Phase II: Urothelial carcinoma Experimental Treatment 1 Intervention

Histologically or cytologically documented, incurable, locally advanced or metastatic cancer

Group II: Phase II: Triple Negative Breast Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically , incurable, locally advanced or metastatic cancer

Group III: Phase II: Non-Small Cell Lung Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group IV: Phase II: Head and Neck Squamous Cell Carcinoma Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group V: Phase II: HR+/ HER2- Breast Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group VI: Phase II: Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma Experimental Treatment 1 Intervention

Histologically or cytologically documented, incurable, locally advanced or metastatic cancer

Group VII: Phase II: Extensive-stage Small Cell Lung Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group VIII: Phase II: Epithelial Ovarian Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group IX: Phase II: Endometrial carcinoma Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group X: Phase II: Cervical Cancer Experimental Treatment 1 Intervention

Histologically or cytologically documented, incurable, locally advanced or metastatic cancer

Group XI: Phase I: Dose Escalation Experimental Treatment 1 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 for the following indications:

Approved in China as SKB264 for:

• Triple-negative breast cancer
• EGFR-mutated non-small cell lung cancer

Who Is Running the Clinical Trial?

Klus Pharma Inc.

Lead Sponsor

Trials

4

Recruited

2,100+

Findings from Research

Trop2 is a protein that is overexpressed in many cancers, making it a promising target for cancer therapies, particularly in metastatic triple-negative breast cancer where the anti-Trop2 drug Trodelvy™ has been approved.

Research is ongoing to explore the effectiveness of Trop2-targeted treatments in other types of tumors, as the expression and role of Trop2 can vary significantly across different cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer. Liu, X., Deng, J., Yuan, Y., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Targeting Trop-2 in solid tumors: future prospects. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting Trop-2 in cancer: Recent research progress and clinical application. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Expression and clinical significance of Trop-2 in human pancreatic cancer]. [2011]

5. England pubmed.ncbi.nlm.nih.gov

Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer. [2023]