Clinical trial NCT04424641: A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Patients With Malignant Solid Tumors
Official title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1044 in Subjects With Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Locally Advanced or Metastatic Solid Tumor(s)
Prostate Cancer
Esophageal Cancer
Triple Negative Breast Cancer (TNBC)
Squamous Cell Carcinoma of Head and Neck (SCCHN)
Non-small Cell Lung Cancer (NSCLC)
Bladder Cancer
Uterine Cancer
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2020-06-11
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of the trial is to evaluate the safety, determine the recommended Phase 2 dose (RP2D), and assess preliminary clinical activity of GEN1044 in patients with solid tumors.

Detailed description: The trial is an open-label, multi-center safety trial of GEN1044. The trial consists of two parts: a dose-escalation part (Phase 1) and an expansion part (Phase 2a). The expansion part of the trial will be initiated once the RP2D has been determined from Phase 1.

Eligibility criteria: Key Inclusion Criteria:

Dose-escalation part:

• Patient with locally advanced or metastatic solid tumor(s) (excluding patients with primary central nervous system \[CNS\] tumors), who has experienced disease progression while on standard therapy or is intolerant of, or not eligible for, standard therapy.

Expansion part:

• Must have an advanced or metastatic, pathologically confirmed diagnosis of one of the following tumors: Uterine Cancer, Prostate Cancer, Esophageal Cancer, TNBC, SCCHN, NSCLC (both adenocarcinoma \[ACC\] and squamous cell carcinoma \[SCC\], Bladder Cancer.

Both parts:

* Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the trial, and is willing to participate in the trial prior to any trial related assessments or procedures.
* Must have measurable disease according to response assessment criteria relevant to the tumor type.
* Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1.
* A woman of reproductive potential must agree to use adequate contraception during the trial and for 4 months after the last GEN1044 administration. Adequate contraception is defined as highly effective methods of contraception.

Key Exclusion Criteria (both parts):

1. Has an uncontrolled intercurrent illness, including but not limited to:

   1. Ongoing or active infection requiring intravenous treatment with anti-infective therapy
   2. Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
   3. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.
   4. Ongoing or recent evidence of significant autoimmune disease. Patients with a history of grade 3 or higher immune-related adverse events that led to treatment discontinuation.
   5. Patients with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
   6. History of chronic liver disease or evidence of hepatic cirrhosis.
   7. History of non-infectious pneumonitis that has required steroids, or currently has pneumonitis.
   8. History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1044.
   9. Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
2. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke.
3. Prior therapy:

   Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed.
4. Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved.
5. Has a history of ≥ grade 2 cytokine release syndrome (CRS) with other CD3-based bispecifics, or a history of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or has known allergies, hypersensitivity, or intolerance to GEN1044 or its excipients.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From Day 1 to Day 21 of first cycle
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through Day 263 (corresponding to maximum observed duration)
measure: Number of Participants With Abnormal Laboratory Values
timeFrame: Day 1 through Day 263 (corresponding to maximum observed duration)
Secondary outcomes:
measure: Number of Participants With Complete Response (CR) or Partial Response (PR)
timeFrame: Day 1 through Day 233
measure: Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044
timeFrame: Day 1 through Day 263 (predose on Day 1 of Cycles 1, 2, 3, 5, 7, and then on Day 1 of every 4 cycles thereafter, end of treatment [EOT], and 30 days after last study drug)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Tennesse Oncology, PLLC - Nashville
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Copenhagen
country: Denmark
facility: Rigshospitalet (Copenhagen University Hospital)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
Study officials:
affiliation: Genmab
name: Roberto Oliveri, MD
role: STUDY_DIRECTOR
References:
citation: Kemper K, Gielen E, Boross P, Houtkamp M, Plantinga TS, de Poot SA, Burm SM, Janmaat ML, Koopman LA, van den Brink EN, Rademaker R, Verzijl D, Engelberts PJ, Satijn D, Sasser AK, Breij EC. Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models. Life Sci Alliance. 2022 Sep 8;5(11):e202201481. doi: 10.26508/lsa.202201481. Print 2022 Nov.