DCSZ11 + Pembrolizumab for Advanced Cancer

Recruiting at 34 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: DynamiCure Biotechnology

Must not be taking: Immunosuppressants, Anticancer treatments

Disqualifiers: Second malignancy, Thrombotic events, Heart failure, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing DCSZ11, a drug that helps the immune system attack cancer cells by targeting a specific protein. It is aimed at patients with advanced or metastatic solid tumors. The study will determine the best dose and assess its effectiveness both alone and in combination with another drug, pembrolizumab, which has shown efficacy in various cancers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received systemic anticancer treatments or investigational products within 14 days before the first dose of the study drug.

What data supports the effectiveness of the drug DCSZ11 + Pembrolizumab for advanced cancer?

Pembrolizumab has shown strong antitumor activity and improved survival rates in various advanced cancers, including non-small-cell lung cancer and tumors with specific genetic features, when used alone or with other drugs. This suggests it could be effective in combination with DCSZ11 for advanced cancer. ^{1 2 3 4 5}

What safety data exists for Pembrolizumab in humans?

Pembrolizumab is generally considered safe for treating advanced cancers, but some patients may experience immune-related side effects, such as interstitial nephritis (a type of kidney inflammation). It has been studied in various cancers, including non-small cell lung cancer, and is usually well-tolerated, though complications can occur. ^{1 4 6 7 8}

What makes the drug DCSZ11 + Pembrolizumab unique for advanced cancer?

The combination of DCSZ11 with pembrolizumab is unique because it pairs a potentially novel agent (DCSZ11) with pembrolizumab, an established immunotherapy that works by blocking the PD-1 pathway to help the immune system attack cancer cells. This combination may offer a new approach for treating advanced cancers, especially if DCSZ11 has a different mechanism or targets compared to existing treatments. ^{1 4 5 9 10}

Eligibility Criteria

Adults with advanced or metastatic solid tumors, such as colorectal, lung, breast cancer and more, who have tried all other active treatments without success. They must be in a stable condition with good organ function and agree to use contraception. Those with severe heart issues, uncontrolled diseases like pulmonary conditions or infections, recent major surgeries or certain blood clots are excluded.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My recent tests show my organs and bone marrow are functioning well.

I am a man who agrees to not have sex or use birth control and not donate sperm.

Exclusion Criteria

I haven't taken any cancer drugs or been in a trial for at least 14 days.

My surgical wounds from recent surgery are fully healed and not infected.

I stopped immunotherapy due to severe side effects.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of DCSZ11 as monotherapy and in combination with pembrolizumab to assess safety and tolerability

Varies

Multiple visits to the clinic

Dose Expansion

Participants receive selected doses of DCSZ11 in combination with pembrolizumab to further investigate safety, tolerability, and antitumor activity

Varies

Multiple visits to the clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• DCSZ11 (Monoclonal Antibodies)

Trial Overview The trial is testing DCSZ11 alone and combined with Pembrolizumab in patients with various types of solid tumors that haven't responded to standard therapies. It's an early-phase study looking at how well these drugs work together for treating cancer.

Participant Groups

Group I: Phase 1b Dose Expansions Experimental Treatment 2 Interventions

Dose expansion to further investigate the safety, tolerability, and preliminary evidence of antitumor activity of the combination with pembrolizumab in select tumor indications.

Group II: Phase 1a Dose Escalation Monotherapy Experimental Treatment 1 Intervention

Dose escalation to investigate the safety and tolerability of DCSZ11.

Group III: Phase 1a Dose Escalation Combination Experimental Treatment 2 Interventions

Dose escalation to investigate safety and tolerability, and determine DCSZ11 Phase 1b doses in combination with pembrolizumab.

Who Is Running the Clinical Trial?

DynamiCure Biotechnology

Lead Sponsor

Trials

2

Recruited

260+

Findings from Research

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab was found to be safe and well tolerated in a phase I study involving 20 patients with advanced solid tumors, with no dose-limiting toxicities observed at doses up to 10 mg/kg every 2 weeks.

The treatment demonstrated durable antitumor activity, with complete responses in two patients and stable disease in 15 others, indicating that a minimum effective dose for antitumor activity is 2 mg/kg every 3 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Patnaik, A., Kang, SP., Rasco, D., et al.[2022]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

In a study involving 351 patients with advanced noncolorectal MSI-H/dMMR solid tumors, pembrolizumab showed a significant objective response rate (ORR) of 30.8%, indicating its efficacy in this patient population.

The treatment demonstrated a long median duration of response of 47.5 months and manageable safety, with only 11.1% of patients experiencing severe (grade 3-4) treatment-related adverse events, supporting its use in heavily pretreated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Maio, M., Ascierto, PA., Manzyuk, L., et al.[2022]

In a study of 38 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, the median overall survival was 11.08 months, indicating that the drug is a viable treatment option for this patient group.

The study found that while pembrolizumab's effectiveness in real-life settings appears lower than in clinical trials, it still provides significant benefits, particularly for patients with high PD-L1 expression, and highlights the importance of monitoring for immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of pembrolizumab in patients with non-small cell lung cancer: a retrospective observational study. Cavaille, F., Peretti, M., Garcia, ME., et al.[2022]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

A 62-year-old patient with advanced non-small-cell lung cancer developed interstitial nephritis after seven cycles of treatment with pembrolizumab, leading to a decline in kidney function and eventual discontinuation of the drug.

Although renal adverse events are rare (reported in less than 3% of patients), this case highlights the importance of monitoring kidney function during pembrolizumab treatment, as early detection of issues like increased serum creatinine levels can aid in management, even if full recovery of kidney function is not guaranteed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial nephritis with pembrolizumab: A case report and review. Peláez Bejarano, A., Montero Pérez, O., Inoriza Rueda, A., et al.[2021]

In a phase 2 trial involving 12 patients with advanced osteosarcoma, pembrolizumab showed no clinical benefit at 18 weeks, with all patients experiencing disease progression and a median overall survival of only 6.6 months.

Despite the lack of significant antitumor activity, pembrolizumab was well-tolerated, with no treatment-related deaths or severe adverse events, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Boye, K., Longhi, A., Guren, T., et al.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

References

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

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

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. [2022]

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]

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

Real-world efficacy and safety of pembrolizumab in patients with non-small cell lung cancer: a retrospective observational study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Interstitial nephritis with pembrolizumab: A case report and review. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]