DCSZ11 as a Monotherapy and in Combination in Patients With Advanced or Metastatic Solid Tumors

NCT05785754 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DCSZ11-101
• Study Type: interventional
• Target: 320
• Locations: 4 countries
• Sites: 35

Brief Summary

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 solid tumors. The study consists of an Escalation Phase (Phase 1a) and a Dose Expansion/Optimization Phase (Phase 1b).

Conditions

Advanced or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Phase 1a: Incidence of dose limiting toxicites (DLTs)

  21 days

• Phase 1a: Frequency and severity of treatment emergent adverse events

  up to 3 years

• Phase 1b: Overall response rate (ORR) per Investigator-assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST)

  1 year

Secondary Outcomes (8)

• Phase 1a: Overall response rate (ORR) per Investigator-assessed RECIST v1.1

  1 year

• Phase 1a and b: Overall response rate (ORR) per Investigator-assessed consensus guideline developed by the RECIST Working Group for the use of modified RECIST, Version 1.1 in cancer immunotherapy trials (iRECIST)

  1 year

• Phase 1a and b: Duration of response (DOR) as determined per Investigator assessment by RECIST v1.1 and iRECIST

  1 year

• Phase 1 a and b: Disease control rate (DCR) as determined per Investigator assessment by RECIST v1.1 and iRECIST.

  1 year

• Phase 1a and b: Progression free survival (PFS) as determined per Investigator assessment by RECIST v1.1 and iRECIST.

  3 years

Study Arms (4)

Phase 1a Dose Escalation Monotherapy

EXPERIMENTAL

Dose escalation to investigate the safety and tolerability of DCSZ11.

Drug: DCSZ11

Phase 1a Dose Escalation Combination

EXPERIMENTAL

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

Drug: DCSZ11; Drug: Pembrolizumab

Phase 1b Dose Expansions

EXPERIMENTAL

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

Drug: DCSZ11; Drug: Pembrolizumab

Phase 1b Standard of Care

EXPERIMENTAL

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

Drug: Doxorubicin; Drug: Tebentafusp

Interventions

DCSZ11 DRUG

A monoclonal antibody that binds to CD93, DCSZ11 will be administered as a single intravenous (IV) infusion on Day 1 in each 21-day cycle.

Phase 1a Dose Escalation Combination; Phase 1a Dose Escalation Monotherapy; Phase 1b Dose Expansions

Pembrolizumab DRUG

Pembrolizumab injection

Phase 1a Dose Escalation Combination; Phase 1b Dose Expansions

Doxorubicin DRUG

1b SOC Cohort 1: Doxorubicin combination in soft tissue sarcoma

Phase 1b Standard of Care

Tebentafusp DRUG

1b SOC Cohort 2: Tebentafusp combination in uveal melanoma

Phase 1b Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age.
• Be willing and able to provide written informed consent for the study.
• Patients in Phase 1a must have a histologically or cytologically documented, advanced (metastatic and/or unresectable) solid tumor that has progressed on or after standard therapy (relapsed/refractory patients; patients must have failed at least one prior line of therapy) or for whom there is no effective standard therapy based on the Investigator's judgment.
• Note: Patients with glioblastoma (GBM) or other central nervous system(CNS) tumors may participate if they are on stable or decreasing corticosteroid levels not exceeding 2 mg/day dexamethasone (or equivalent doses of other corticosteroids) within 7 days of the first dose of study drug or do not require corticosteroids.
• Note: For patients who are intolerant to or refuse standard-of-care therapy for recurrent disease, reasons must be documented.
• Patients in Phase 1b Dose Optimization/Expansion must have one of the following:
• Non-squamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed and that has progressed to no more than 2 prior systemic therapies. Patients must not have presented with disease progression during the first 3 months of treatment with first line anti-PD-(1/L1)-containing therapy. Patients must have had documented disease progression per RECIST 1.1 within 12 weeks from the last dose of anti-PD-1/L1 mAb to be considered to have failed an anti-PD-(1/L1) mAb containing therapy. The initial evidence of disease progression to anti-PD-1/L1 mAb containing therapy needs to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression.
• Note: Patients with known driver mutations/genomic aberrations (i.e., EGFR, B-Raf proto-oncogene mutation V600E \[BRAF V600E\], and ROS proto-oncogene 1 \[ROS1\] sensitizing mutations, neurotrophic receptor tyrosine kinase \[NRTK\] gene fusions, and ALK rearrangements) are not eligible.
• Note: Patients with rapid clinical progression are excluded from participation.
• Immunotherapy-naïve microsatellite stable-CRC (MSS-CRC) that failed or was intolerant to ≥ 2 lines of therapy and that progressed on/after no more than 4 lines of therapy.
• Note: Patients must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated. Patients eligible for treatment with an approved and available targeted therapy must have been offered such therapy prior to enrollment. Adjuvant chemotherapy will be considered a prior line of therapy if the patient progressed while on or within 6 months of completing adjuvant treatment.
• Patients in Phase 1b Standard-of-Care Combination Lead-in/Expansions must have one of the following:
• Histologically confirmed, anthracycline naïve, metastatic or locally advanced, unresectable soft-tissue sarcoma for which doxorubicin monotherapy is indicated. Note: Ewing sarcoma, gastrointestinal stromal tumor (GIST), and Kaposi sarcoma are excluded.
• Histologically confirmed, metastatic or advanced, unresectable uveal melanoma that are eligible for treatment with tebentafusp monotherapy. Patients should not have received more than 4 doses of tebentafusp at the target dose level of 68 mcg.
• Patients must have a lesion not previously irradiated that can be biopsied with acceptable clinical risk and agree to have a fresh biopsy at Screening and on treatment; except patients with GBM or other CNS tumors. Every effort must be made to take the second biopsy from the same lesion of the biopsy at Screening.

You may not qualify if:

• Received systemic anticancer treatments or investigational products within 28 days before the first dose of study drug or 5 half-lives, whichever is shorter.
• Note: Low-dose steroids (oral prednisone ≤10 mg per day or equivalent), hormonal therapy for prostate cancer or breast cancer (as adjuvant treatment), and treatment with bisphosphonates and receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors are allowed.
• Received extended field radiotherapy ≤4 weeks before the start of treatment (≤7 days for limited field radiation for palliation outside the chest or brain) or has radiation related toxicities requiring corticosteroid treatment.
• Patients with second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the patient is not on active anticancer therapy. These patients must be discussed with the Sponsor prior to enrollment.
• Patients with known active CNS metastases and or carcinomatous meningitis.
• Systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 3 months prior to the first dose of study drug
• Systemic venous thrombotic events (e.g., deep vein thrombosis) or pulmonary arterial events (e.g., pulmonary embolism) within 1 month prior to the first dose of study drug. Patients with venous thrombotic events prior to the first dose of study drug on stable anticoagulation therapy are eligible.
• Left ventricular ejection fraction (LVEF) \< 50%.
• Major surgery within 4 weeks and minor surgery within 2 weeks of the first dose of study drug; following surgeries, all surgical wounds must be healed and free of infection or dehiscence. Patients must have recovered and not have ongoing surgical complications.
• Marked proteinuria ≥ 2 g/24 hours and/or nephrotic syndrome. Patients with proteinuria 2+ or greater urine dipstick reading should undergo further assessment, e.g., a 24-hour urine collection.
• Known allergy or hypersensitivity to any component of the study drugs or, for patients receiving the imaging agent, any component of the imaging agent.
• For patients receiving a combination with pembrolizumab:
• Received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
• Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Autoimmune disease requiring systemic immunosuppressive therapy within the past 2 years. Hormone therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered an excluded form of systemic treatment of an autoimmune disease.

Sponsors & Collaborators

• DynamiCure Biotechnology: lead

Study Sites (35)

University of Alabama

Birmingham, Alabama, 35294, United States

RECRUITING

Mayo Clinic

Phoenix, Arizona, 85054, United States

RECRUITING

HonorHealth

Scottsdale, Arizona, 85258, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Sarah Cannon Research Institute Denver Healthone

Denver, Colorado, 80218, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06519, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

John Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

COMPLETED

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

MonteFiore

The Bronx, New York, 10461, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

RECRUITING

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

RECRUITING

University of Sunshine Coast

Buderim, Queensland, 4556, Australia

WITHDRAWN

Southern Oncology Clinical Research Unit (SOCRU)

Bedford Park, South Australia, 5042, Australia

RECRUITING

The Queen Elizabeth Hospital (TQEH)

Woodville South, South Australia, 5011, Australia

RECRUITING

Monash Health

Clayton, Victoria, 3168, Australia

RECRUITING

Cabrini Hospital

Malvern, Victoria, 3144, Australia

COMPLETED

Linear Clinical Research Limited

Nedlands, Western Australia, 6009, Australia

RECRUITING

Townsville Hospital

Douglas, QLD4810, Australia

RECRUITING

Liverpool Hospital

Liverpool, NSW2170, Australia

COMPLETED

Mater Misericordiae Health Services Brisbane Ltd

South Brisbane, QLD4101, Australia

RECRUITING

Sydney Adventist Hospital

Wahroonga, Australia

WITHDRAWN

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

RECRUITING

Dong-a University Hospital

Busan, 49201, South Korea

RECRUITING

Cha University Bundang Medical Center

Gyeonggi-do, 13496, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

WITHDRAWN

Kaohsiung Medical University Chung-ho Memorial Hospital

Kaohsiung City, 807, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

MeSH Terms

Interventions

pembrolizumab; Doxorubicin; tebentafusp

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Sr Medical Director

CONTACT

+1 (781) 373-9136; alejandrogomez@dynamicure.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: March 27, 2023
• Study Start: June 28, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); KR (5); TW (4); AU (12)