DCSZ11 + Pembrolizumab for Advanced Cancer

Recruiting at 36 trial locations

Overseen By Sr Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: DynamiCure Biotechnology

Must not be taking: Immunosuppressants, Anticancer treatments

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

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

Compensation: Varies

Number of Visits: Unknown

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called DCSZ11 for individuals with advanced or spreading solid tumors. It examines how DCSZ11 works alone and with pembrolizumab to assess its potential in fighting cancer. The trial includes various parts to determine the optimal dose and combination with standard treatments like doxorubicin for soft tissue sarcoma and tebentafusp for uveal melanoma. Individuals with advanced cancer unresponsive to standard treatments might be suitable for this trial. Participants should have a tumor that can be biopsied and meet other specific health criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that DCSZ11, whether used alone or with pembrolizumab, remains in the early testing stages, so limited safety information is available. Previous patients have demonstrated that pembrolizumab is generally safe for treating advanced cancers, though it can cause side effects like tiredness or skin problems.

Since DCSZ11 is being tested in a Phase 1 trial, the main goal is to assess its safety and determine the right dose. Researchers are just beginning to evaluate how well people can tolerate it. Current studies are crucial for understanding more about DCSZ11’s safety, especially when combined with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DCSZ11 because it represents a novel approach to treating advanced cancers, which traditionally rely on chemotherapy, radiation, or surgery. Unlike these standard treatments, DCSZ11 is being tested in combination with pembrolizumab, an immunotherapy drug that helps the immune system target cancer cells more effectively. This combination has the potential to enhance the body's natural defenses against cancer, offering a promising new avenue for patients with limited options. Additionally, DCSZ11 is being explored in different dosing strategies and combinations, such as with doxorubicin for soft tissue sarcoma and tebentafusp for uveal melanoma, which could lead to more personalized and effective treatment regimens.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that pembrolizumab can effectively shrink tumors and extend the lives of people with various advanced cancers. It has been particularly successful in treating non-small-cell lung cancer and other tumors with specific markers. In this trial, researchers are testing a new drug, DCSZ11, to determine if it can enhance these effects when combined with pembrolizumab for advanced or spreading solid tumors. DCSZ11 is an anti-CD93 monoclonal antibody that targets a protein involved in tumor growth and spread. Participants in this trial may receive either the combination of DCSZ11 and pembrolizumab or DCSZ11 alone, as researchers assess the safety and effectiveness of these treatments in combating advanced cancers. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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

For female patients of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test and agree to use highly effective contraception

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• DCSZ11

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.

How Is the Trial Designed?

Group I: Phase 1b Standard of Care Experimental Treatment 2 Interventions

Phase 1b - Standard-of-Care (SOC) Combinations Safety Lead-in/ Expansion in Select Indications A safety lead-in using the BOIN design followed by a Simon two-stage like design will be used to evaluate DCSZ11 in combination with standard of care in select indications. Patients will receive DCSZ11 IV at one of the dose escalation dose levels/schedule (or dose/schedule selected for optimization/expansion). Once the safety lead-in is completed, a Bayesian continuous toxicity monitoring will be used to monitor for unacceptable toxicity in expansions. The following SOC combination expansion cohorts will be enrolled: * 1b SOC Cohort 1: Doxorubicin combination in soft tissue sarcoma * 1b SOC Cohort 2: Tebentafusp combination in uveal melanoma

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

Dose escalation to investigate the safety and tolerability of DCSZ11.

Group IV: 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+

Published Research Related to This Trial

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 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]

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 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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05785754

Study Details | NCT05785754 | DCSZ11 as a Monotherapy ... This is a multicenter, open-label, Phase 1 study to assess the effects of DCSZ11 as a monotherapy and in combination in patients with advanced or metastatic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07035249

DCSZ11 in Combination With Standard Therapy ... Patients will receive DCSZ11 at 800 mg Q3W. Drug : Standard Treatment. The available standard treatment for head and neck cancer patients.

3. mayo.edu mayo.edu/research/clinical-trials/cls-20560567

DCSZ11 as a Monotherapy in Patients With Advanced or ... The purpose of this study is to assess the effects of DCSZ11, an anti-CD93 monoclonal antibody, as a monotherapy in patients with advanced or metastatic solid ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-4-2023-dc3e8

DCSZ11 + Pembrolizumab for Advanced Cancer Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile ...

5. synapse.patsnap.com synapse.patsnap.com/drug/d72df45c476747ab86f8dad0ee1b0032

DCSZ-11 - Drug Targets, Indications, Patents The study is designed to evaluate the safety and efficacy of DCBY02 in adult patients with a wide range of advanced cancers. CD93 is a novel ...

6. clinrol.com clinrol.com/study/NCT05785754

DCSZ11 in Advanced Solid Tumors Study details: The drug being tested in this study is called DCSZ11. DCSZ11 is being tested to treat people who have advanced or metastatic solid tumors.