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

• ClinicalTrials.gov Identifier: NCT05785754
• Recruitment Status: Recruiting
• First Posted: March 27, 2023
• Last Update Posted: March 5, 2024
• Sponsor: DynamiCure Biotechnology
• Information provided by (Responsible Party): DynamiCure Biotechnology

Tracking Information

• First Submitted Date: March 14, 2023
• First Posted Date: March 27, 2023
• Last Update Posted Date: March 5, 2024
• Actual Study Start Date: June 28, 2023
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2023)

• Phase 1a: Incidence of dose limiting toxicites (DLTs) [ Time Frame: 21 days ]
• Phase 1a: Frequency and severity of treatment emergent adverse events [ Time Frame: up to 3 years ]
• Phase 1b: Overall response rate (ORR) per Investigator-assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) [ Time Frame: 1 year ]

Original Primary Outcome Measures (submitted: March 14, 2023)

• Part 1B/2B: Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [ Time Frame: 2 years ]
• Part 1B: The proportion of patients experiencing dose limiting toxicity (DLT) events [ Time Frame: 28 days ]

Current Secondary Outcome Measures (submitted: November 7, 2023)

• Phase 1a: Overall response rate (ORR) per Investigator-assessed RECIST v1.1 [ Time Frame: 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) [ Time Frame: 1 year ]
• Phase 1a and b: Duration of response (DOR) as determined per Investigator assessment by RECIST v1.1 and iRECIST [ Time Frame: 1 year ]
• Phase 1 a and b: Disease control rate (DCR) as determined per Investigator assessment by RECIST v1.1 and iRECIST. [ Time Frame: 1 year ]
• Phase 1a and b: Progression free survival (PFS) as determined per Investigator assessment by RECIST v1.1 and iRECIST. [ Time Frame: 3 years ]
• Phase 1 a and b: Overall survival (OS) [ Time Frame: 3 years ]
• Phase 1 and b: Pharmacokinetic parameters of DCSZ11 [ Time Frame: 2 years ]
• Phase 1 a and b: Incidence of anti-drug antibody (ADA) and neutralizing antibodies (NAbs) against DCSZ11 [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: March 14, 2023)

• Parts 1B: Objective response rate (ORR) as determined per Investigator assessment [ Time Frame: 1 year ]
• Parts 1B: Duration of response (DOR) as determined per Investigator assessment [ Time Frame: 1 year ]
• Parts 1B: Disease control rate (DCR) as determined per Investigator assessment [ Time Frame: 1 year ]
• Parts 1B: Progression free survival (PFS) as determined per Investigator assessment [ Time Frame: 1 year ]
• Parts 1B: Overall survival (OS) [ Time Frame: 1 year ]
• Parts 1B/2B: Pharmacokinetic parameters of DCSZ11: maximum observed concentration (Cmax) [ Time Frame: 2 years ]
• Parts 1B/2B: Pharmacokinetic parameters of DCSZ11: area under the concentration-time curve (AUC) [ Time Frame: 2 years ]
• Parts 1B/2B: Pharmacokinetic parameters of DCSZ11: clearance (CL) [ Time Frame: 2 years ]
• Parts 1B/2B: Pharmacokinetic parameters of DCSZ11: volume of distribution (Vz) [ Time Frame: 2 years ]
• Parts 1B/2B: Pharmacokinetic parameters of DCSZ11: half-life (t1/2) [ Time Frame: 2 years ]
• Parts 1B/2B: Incidence of anti-drug antibody (ADA) and neutralizing antibodies (NAbs) against DCSZ11 [ Time Frame: 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DCSZ11 as a Monotherapy and in Combination in Patients With Advanced or Metastatic Solid Tumors
• Official Title: A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of DCSZ11 as a Monotherapy and in Combination in Patients With Advanced or Metastatic Solid Tumors
• Brief Summary: This is a multicenter, open-label, Phase 1 study to assess the effects of DCSZ11, an anti-CD93 monoclonal antibody, as a monotherapy and in combination in patients with advanced or metastatic solid tumors.

Detailed Description

The drug being tested in this study is called DCSZ11. DCSZ11 is being tested to treat people who have advanced or metastatic solid tumors. The study will include a dose escalation phase and a dose expansion phase.

The study will enroll approximately 138 patients in dose escalation, and approximately 113 participants in the dose expansion phase. Participants will receive escalating doses of DCSZ11 and a fixed dose of pembrolizumab until DCSZ11 doses for phase 1b are selected:

• Phase 1a DCSZ11 monotherapy Dose Escalation.
• Phase 1a DCSZ11 in combination with fixed dose of pembrolizumab Dose Escalation.

Once Phase 1b doses are selected for Phase 1b, participants of select advanced or metastatic solid tumors will receive DCSZ11 in below defined cohorts in Phase 1b:

• Phase 1b cohort 1 NSCLC.
• Phase 1b cohort 2 Microsatellite Stable Colorectal Cancer (MSS-CRC) without liver involvement.
• Phase 1b cohort 3 MSS-CRC with liver involvement.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 60 months. Participants will make multiple visits to the clinic, and survival follow-up for a maximum of up to 12 months after the last dose of the study drug.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced or Metastatic Solid Tumors

Intervention

• Drug: DCSZ11
  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.
• Drug: Pembrolizumab
  Pembrolizumab injection

Study Arms

• Experimental: Phase 1a Dose Escalation Monotherapy
  Dose escalation to investigate the safety and tolerability of DCSZ11.
  Intervention: Drug: DCSZ11
• Experimental: Phase 1a Dose Escalation Combination
  Dose escalation to investigate safety and tolerability, and determine DCSZ11 Phase 1b doses in combination with pembrolizumab.
  Interventions:

  • Drug: DCSZ11
  • Drug: Pembrolizumab
• Experimental: Phase 1b Dose Expansions
  Dose expansion to further investigate the safety, tolerability, and preliminary evidence of antitumor activity of the combination with pembrolizumab in select tumor indications.
  Interventions:

  • Drug: DCSZ11
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 4, 2024): 257
• Original Estimated Enrollment (submitted: March 14, 2023): 96
• Estimated Study Completion Date: May 2025
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Selected Inclusion Criteria:

1. Male or female patients ≥ 18 years of age.
2. 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.
3. At least 1 measurable lesion according to RECIST Version 1.1.
4. Patients must have a lesion that can be biopsied with acceptable clinical risk and agree to have a biopsy at Screening and on treatment.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
6. Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug.
7. 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.
8. For men who are not surgically sterile must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm.
9. The patient is capable of understanding and complying with the protocol and has signed the required ICF. The appropriate ICF must be signed before relevant study procedures are performed. If applicable, the female partner of a male patient understands and signs the pregnant partner's ICF.

Selected Exclusion Criteria:

1. Received systemic anticancer treatments or investigational products within 14 days before the first dose of the study drug or 5 half-lives, whichever is shorter.
2. Received extended field radiotherapy ≤4 weeks before the start of treatment (≤7 days for limited field radiation for palliation outside the chest or brain).
3. 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.
4. 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.
5. Systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, 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.
6. Left ventricular ejection fraction (LVEF) < 50%
7. 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.
8. Marked proteinuria ≥ 2 g/24 hours and/or nephrotic syndrome. Patients with proteinuria 2+ or greater urine dipstick reading should undergo further assessment, eg, a 24-hour urine collection.

9. For patients receiving a combination with pembrolizumab:

   1. History of adverse events related to immunotherapy that required treatment discontinuation.
   2. History of autoimmune disease requiring systemic immunosuppressive therapy with daily doses of prednisone >10 mg/day or equivalent doses, or any other form of immunosuppressive therapy. 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.
   3. History of noninfectious pneumonitis that required steroids or a history of interstitial lung disease.
   4. Evidence of active, noninfectious pneumonitis.
   5. History of allogeneic tissue or solid organ transplant.
10. History of any of the following ≤6 months before first dose: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias >Grade 2, or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
11. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent.
12. Female patients who are pregnant or lactating and breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sr Medical Director; +1 (781) 373-9136; alejandrogomez@dynamicure.com

• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT05785754
• Other Study ID Numbers: DCSZ11-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: DynamiCure Biotechnology
• Original Responsible Party: Same as current
• Current Study Sponsor: DynamiCure Biotechnology
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: DynamiCure Biotechnology
• Verification Date: March 2024