Magrolimab in Combination With Cytotoxic Chemotherapy in Advanced Urothelial Carcinoma

NCT05738161 | Withdrawn Phase 1

• 2 other identifiers: CO-SW-548-63472023-00258
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

In their "Magrolimab" research project, the investigators want to find out whether the new drug Magrolimab in combination with conventional chemotherapy is well tolerated and whether survival or progression-free survival improves.

Conditions

Advanced Urothelial Carcinoma

Keywords

Chemotherapy; Antibody Drug Therapy

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity in Run-in Phase

  Incidence of DLTs in participants of the safety run-in phase

  End of cycle 1 (day 21)

• Proportion of participants with any AEs of severity grade 3 or higher

  Proportion of participants with any AEs of severity grade 3 or higher according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 over 6 months after IMP dose initiation

  Up to 6 months after IMP dose initiation

Secondary Outcomes (4)

• Progression-Free Survival

  48 months

• Duration Of Response

  48 months

• Date of dose initiation to death

  48 months

• Proportion of complete or partial response (ORR)

  48 months

Other Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  48 months

• Reported AEs

  From start of treatment with IMP until 28 days after the last IMP dose or the initiation of subsequent anticancer therapy, whichever is sooner

Study Arms (1)

Magrolimab in combination with Cisplatin and Gemcitabine

EXPERIMENTAL

Magrolimab therapy in combination with standard first line platinum-based chemotherapy (with Cisplatin / Gemcitabine) in advanced urothelial carcinoma.

Drug: Magrolimab; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Magrolimab DRUG

Magrolimab in combination with cytotoxic chemotherapy in advanced urothelial carcinoma

Also known as: Hu-5F9-G4

Magrolimab in combination with Cisplatin and Gemcitabine

Cisplatin DRUG

Standard first line platinum-based chemotherapy in advanced urothelial carcinoma

Also known as: L01XA01 Cisplatin

Magrolimab in combination with Cisplatin and Gemcitabine

Gemcitabine DRUG

Standard first line platinum-based chemotherapy in advanced urothelial carcinoma

Also known as: L01BC05 Gemcitabine

Magrolimab in combination with Cisplatin and Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Written informed consent before trial treatment and prior to any trial specific procedures.
• Male or female age ≥ 18 years.
• Histologically confirmed locally advanced or metastatic predominant urothelial carcinoma of the bladder or the upper urinary tract being considered not suitable for curative multimodality treatment including surgery by a multidisciplinary tumor board. All histological subtypes eligible if urothelial carcinoma predominant (exception: Small cell component).
• ECOG performance status 0-2 within 7 days prior to IMP treatment start.
• Bone marrow function (within 14 days prior to IMP treatment start): Hemoglobin ≥ 100 g/L, absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L.
• Hepatic function (within 14 days prior to IMP treatment start): Bilirubin ≤ 1.5 x ULN (except for patients with documented history of Gilbert's disease or genetic equivalent ≤ 3.0 x ULN and primarily unconjugated), AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN.
• Renal function (within 14 days prior to IMP treatment start): eGFR \> 60 mL/min/1.73m., according to CKD-EPI formula.
• Cardiac function (within 28 days prior to IMP treatment start): Left Ventricular Ejection Fraction (LVEF) ≥ 50% as determined by echocardiography (ECHO).
• Women with child-bearing potential are using effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and 6 months after the last dose of IMP. A negative pregnancy test within 7 days prior to IMP treatment start is required for all women with child-bearing potential.
• Men agree not to father a child during trial treatment and 6 months after the last dose of study drug.
• Measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
• Life expectancy at least 12months.
• Willing and able to comply with the requirements and restrictions in this protocol.
• Pre-treatment blood cross-match completed.

You may not qualify if:

• Any pathological evidence of small-cell carcinoma component.
• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years prior to IMP treatment start, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer or low risk localized prostate cancer (T1-T2a, Gleason \<7, PSA \<10 ng/ml).
• Concurrent treatment with Prednisone (or equivalent); except for the prophylactic medication before chemotherapy, treatment of acute hypersensitivity reactions, or chronic treatment (initiated \> 6 months prior to IMP treatment start) at low dose (≤ 10 mg/day of Prednisone or an equivalent corticosteroid).
• Previous treatment with a PD-1, PD-L1, or CTLA4 inhibitor.
• Previous chemotherapy with Cisplatin and Gemcitabine.
• Treatment with an anticancer biologic agent within 4 weeks prior to IMP treatment start or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to IMP treatment start.
• Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of IMP treatment start.
• Current participation in another interventional clinical trial. Patients participating in observational studies are eligible.
• Have known active Central Nervous System (CNS) metastases and / or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking ≤ 10 mg/day of Prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability. Current or prior use of immunosuppressive medication within 28 days prior to IMP treatment start, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids as mentioned above.
• Major surgical procedure within 28 days prior to IMP treatment start.
• Have ongoing AEs not recovered to grade 1 or better due to a previously administered agent.
• (Note: If patients received major surgery, they must have recovered adequately from the toxicity and / or complications from the intervention prior to starting therapy.)
• Preexisting peripheral sensory neuropathy (\> grade 1).
• Uncontrolled diabetes mellitus.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Bern: collaborator
• Swiss National Science Foundation: collaborator

MeSH Terms

Interventions

magrolimab; Cisplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Bernhard Kiss, Professor

  Universtary Hospital Insel Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective investigator-initiated single-arm, phase 1 clinical trial, risk category C

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: February 21, 2023
• Study Start: June 21, 2023
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share