Malignant Solid Tumors, per protocol GCT1047-01 MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: DuoBody®-CD3×B7H4
Product Code: GEN1047
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: GEN1047- DS
CAS Number: 2640279-10-1
Current Sponsor code: GEN1047
Sponsors
Genmab A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Criteria Applicable only to Dose Escalation Part • Subject must have histologically or cytologically confirmed solid tumor(s) in any of the following selected indications for which there is no further available standard therapy likely to confer clinical benefit (or subject is not a candidate or refuses such available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1047 may be beneficial (breast cancer, uterine cancer, ovarian cancer, non-small-cell lung cancer [NSCLC], cervical cancer, head and neck squamous cell carcinoma [HNSCC], urothelial cancer; cholangiocarcinoma [CCA]). Criteria Applicable only to Expansion Part • Subject must have an advanced or metastatic, pathologically confirmed diagnosis of one of the following tumors for which there is no further available standard therapy likely to confer clinical benefit (or subject is not a candidate or refuses such available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1047 may be beneficial (breast cancer, uterine cancer, ovarian cancer, NSCLC, cervical cancer, HNSCC, urothelial cancer; CCA). For all indications: Subjects may have received up to 4 prior systemic treatment regimens for advanced/metastatic disease (maintenance treatment is considered being part of 1 treatment line). Criteria Applicable to Dose Escalation and Expansion Parts • Subjects with ovarian cancer: - Must have documented progressive disease (PD) on or after last prior treatment and within 60 days of Screening. - CA-125 positivity according to the Gynecologic Cancer Intergroup Guideline (GCIG) with a pretreatment sample that is at least twice the upper limit of the reference range and within 2 weeks before starting the treatment. Note: Subjects are not evaluable by CA-125 if they have received mouse antibodies (unless the assay used has been shown not to be influenced by human anti-mouse antibody) or if there has been medical and/or surgical interference with their peritoneum or pleura during the previous 28 days (eg, paracentesis). - Isolated GCIG CA-125 progression does NOT qualify for trial entry. • Must be at least 18 years of age. • Must have either recurrence after, or progression on or lack of response to established standard of care (SOC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting. • Must have at least 1 measurable lesion per RECIST v1.1. The measurable lesion(s) must be outside the field of radiation therapy (RT) if there was prior treatment with RT. • Must have an Eastern Cooperative Oncology Group performance status (ECOG- PS) score of 0 to 1 at Screening and on Cycle 1 Day 1 (C1D1) pretreatment. Note: Do not perform C1D1 ECOG-PS if within 5 days of Screening ECOG-PS. • Must provide a tumor tissue sample during the Screening period and prior to C1D1. A fresh biopsy obtained during Screening may be provided; if a fresh biopsy cannot be obtained, the most recent archival tissue can be submitted if acquired =6 months prior to C1D1. Note: Tumor tissue sample acquired >6 months prior to C1D1 requires sponsor approval on a case-by-case basis. • Must have acceptable laboratory parameters according to the list below: - Glomerular Filtration Rate: =30 mL/min (estimated using Cockcroft-Gault formula) - Total Bilirubin: =1.5× institutional ULN (except Gilbert syndrome, then direct bilirubin =2× institutional ULN) - Aspartate Aminotransferase (AST): =2.
Exclusion criteria
Exclusion criteria: • Cardiovascular Disease - Symptomatic congestive heart failure (NYHA grade III or IV), unstable angina pectoris or cardiac arrhythmia. - Myocardial infarction within 6 months of start of GEN1047. - Uncontrolled hypertension (systolic =160 mmHg and/or diastolic =100 mmHg), despite optimal management. QTc interval >480 msec using Fridericia's QT correction formula. - Other cardiac disease not listed that, in the opinion of the investigator, is/are clinically significant and/or unacceptable. • Central Nervous System - History of intracerebral arteriovenous malformation, cerebral aneurysm, new (within 6 months) or symptomatic brain metastases, spinal cord compression (from disease), or stroke. Transient ischemic attack >1 month before Screening is allowed. - Subjects with unstable CNS metastases and active or history of carcinomatous meningitis are excluded. Subjects with prior treated brain metastases are permitted if they are radiologically stable (no evidence of progression) for at least 28 days by repeat imaging before C1D1. Subjects should be clinically stable and not undergoing steroid taper or have received stereotactic radiation or whole-brain radiation within 14 days before C1D1. Chronic steroid therapy is acceptable provided the dose is stable in the 14 days prior to C1D1 (=10 mg prednisone daily or equivalent, corresponding to a maximum exposure of =140 mg within 14 days). - Subject with new or progressive brain metastases. Spinal cord metastasis is acceptable. Subjects with spinal cord compression are excluded. • Subject has received any of the following in the stated timeframes: - Radiotherapy within 14 days of first GEN1047 dose. Palliative radiotherapy is allowed. - RANK-L inhibitors and bisphosphonates (if on stable dose for =4 weeks) are permitted in this trial. Initiation of growth factors and bisphosphonates is not allowed during the first 4 weeks of GEN1047 administration, unless agreed by the investigator and sponsor medical monitor. - Treatment with investigational or non-investigational anticancer agents (including investigational vaccines) or used an invasive investigational medical device within 28 days or 5 half-lives, whichever is shorter, before the first GEN1047 dose or is currently enrolled in an interventional trial. Subjects in the follow-up phase of an interventional trial may participate if they have not received an investigational agent within 28 days of the first GEN1047 dose. - Prophylaxis with live, attenuated vaccines within 28 days of the first dose of GEN1047; or prophylaxis with the first and/or subsequent injection(s) of SARS-CoV-2 nucleic acid vaccine within 28 days prior to first dose of GEN1047. - Chronic systemic immunosuppressive corticosteroids, ie, prednisone >10 mg daily (or equivalent) or a cumulative dose >140 mg prednisone within 14 days (or equivalent) before the first GEN1047 dose. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted. - Has received granulocyte colony-stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within 2 weeks prior to the first dose of GEN1047 or being chronically transfusion dependent. - Any prior therapy with an antibody targeting CD3 or other T cell activating surface marker. • Toxicities from previous anticancer therapies that have not resolved to baseline levels or to = grade
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation Part: • Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and/or maximum administered dose (MAD) • Characterize the safety profile of GEN1047 Dose Expansion Part: • Evaluate antitumor activity;Primary end point(s): Dose Escalation Part: • Dose-liming toxicities (DLT) • Adverse events (AE) and safety laboratory parameters Dose Expansion Part: • Objective response rate (ORR) based on RECIST v1.1;Secondary Objective: Dose Escalation Part: • Characterize pharmacokinetic (PK) profile • Evaluate immunogenicity of GEN1047 • Evaluate preliminary antitumor activity based on response assessment criteria (Response Evaluation Criteria In Solid Tumors [RECIST] v1.1) Dose Expansion Part: • Evaluate preliminary antitumor activity based on response assessment criteria (RECIST v1.1) • Evaluate preliminary antitumor activity based on CA125 tumor marker in subjects with ovarian cancer • Evaluate preliminary efficacy • Further describe the safety profile of GEN1047 • Further characterize PK profile • Further evaluate immunogenicity of GEN1047;Timepoint(s) of evaluation of this end point: Assessments will be performed at regular intervals during the trial. Please see protocol for detailed schedule of events for Dose Escalation and Dose Expansion Parts. A final safety follow-up visit will be conducted 30 days (+14 days) after the subject receives the last dose of GEN1047. Thereafter, survival status will be assessed by contacting subjects every 3 months (±7 days), beginning from the day of the last dose of GEN1047 and continuing until the subject dies or withdraws from the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation Part: • PK parameters (clearance; volume of distribution; AUClast; AUCinf; Cmax; Tmax; Ctrough; and t1/2) • Anti-drug antibody (ADA) incidence • Antitumor activity, ie, reduction in tumor size according to response assessment (RECIST v1.1) per local review: ORR, disease control rate (DCR), duration of response (DOR), time to response (TTR) Dose Expansion Part: • Antitumor activity, ie, reduction in tumor size according to response assessment (RECIST v1.1) per local review with the option of a central independent imaging review: DCR, DOR, TTR • For ovarian cancer antitumor activity: cancer antigen 125 (CA-125) and modified ORR based on RECIST v1.1 and CA-125 Evaluation of preliminary efficacy: progression free survival (PFS) and overall survival (OS) • AEs and safety laboratory parameters • PK parameters (clearance; volume of distribution; AUClast; AUCinf; Cmax; Tmax; Ctrough; t1/2) • ADA response;Timepoint(s) of evaluation of this end point: Assessments will be performed at regular intervals during the trial. Please see protocol for detailed schedule of events for Dose Escalation and Dose Expansion Parts. A final safety follow-up visit will be conducted 30 days (+14 days) after the subject receives the last dose of GEN1047. Thereafter, survival status will be assessed by contacting subjects every 3 months (±7 days), beginning from the day of the last dose of GEN1047 and continuing until the subject dies or withdraws from the trial. | — |
Countries
Denmark, France, Spain, United States
Contacts
Public ContactClinical Trial Information
Genmab A/S
Outcome results
None listed