Clinical trial NCT03118349: Study of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy
Official title: Phase I, Open-Label, Multi-Center, Dose Escalation With Expansion Trial of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy in Relapse/Refractory Subjects With Pancreatic Cancer or Other CA19-9 Positive Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Carcinoma
Tumors That Express CA 19-9
Keywords: CA19-9 Positive Malignancies
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
First posted: 2017-04-18
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Open label, nonrandomized, dose-escalation with cohort expansion study of MVT-5873/MVT-1075 in subjects with previously treated, Carbohydrate Antigen 19-9 (CA19-9) positive malignancies (e.g., pancreatic adenocarcinoma).

Detailed description: Open label, nonrandomized, dose escalation study of MVT-5873/MVT-1075 to evaluate safety, dosimetry, determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and define the pharmacokinetics of MVT-1075. The population consisted of subjects with CA19-9 positive malignancies (i.e., predominately pancreatic adenocarcinoma) who may benefit from a CA19-9-based radioimmunotherapy.

The study utilized a 3+3 study design to identify the MTD. The RP2D was planned to be no higher than the MTD. An expansion group was planned to receive MVT-5873/MVT-1075 at the RP2D in order to obtain initial estimates of response and additional information on safety.

Eligibility criteria: Inclusion Criteria:

1. Signed, informed consent
2. Age 18 or more years
3. Histologically or cytologically confirmed, previously treated, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies
4. Prior treatment with (or intolerance to) at least one standard systemic regimen for the patient's respective tumor
5. Evidence of tumor expression of CA19-9 based on immunohistochemistry performed on tumor samples or elevated serum levels (≥1.5 x upper limits of normal \[ULN\]) of CA19-9 considered secondary to tumor
6. Evaluable or measurable disease based on RECIST 1.1
7. Recovered from any prior treatment related toxicity to at least Grade 1 with exception of Grade 2 alopecia or other Grade 2 toxicity with prior approval of the Medical Monitor
8. If previously exposed to irradiation, the combined prior and anticipated exposure for Cycle 1 is not expected to exceed organ exposure limits outlined in the study protocol
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or Karnofsky performance status (KPS) of 100% to 80%
10. Adequate hematologic, renal and hepatic laboratory parameters
11. Willingness to participate in collection of pharmacokinetic samples
12. Willingness to use adequate contraception throughout study and for a period of 3 months after last dose of MVT-5873 or MVT-1075 (whichever is later)

Exclusion Criteria:

1. Brain metastases unless previously treated and well controlled for at least 3 months
2. Any tumor mass greater than 10 cm in longest diameter
3. Other known active cancer(s) likely to require treatment in the next two years
4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
5. Prior radiation therapy encompassing more than 25% of the skeleton or prior treatment with 89Strontium or 153Samarium
6. Fewer than 28 days from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation except for:

   1. Ongoing hormonal therapy administered for control of cancer (e.g., breast cancer, prostate cancer), which may be continued throughout the study
   2. MVT-5873 and MVT-2163 administered as part of a different protocol
7. Major surgery other than diagnostic surgery within 28 days of Study Day 1
8. History of anaphylactic reaction to human, or humanized, antibody
9. Pregnant or currently breast-feeding
10. Known to be positive for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
11. Psychiatric illness/social situations that would interfere with compliance with study requirements
12. Significant cardiovascular risk including, but not limited to, recent (within 4 weeks) coronary stenting or myocardial infarction within 6 months

Primary outcomes:
measure: The MTD of MVT-5873/MVT-1075
timeFrame: Through study completion. Estimated at one year
measure: Occurrence of graded adverse events (AEs) in each subject
timeFrame: Through study completion. Estimated at one year
Secondary outcomes:
measure: Specific organ distribution of MVT-1075 as assessed with planar gamma camera
timeFrame: Through study completion. Estimated at one year
measure: Specific organ distribution of MVT-1075 as assessed with single-photon emission computed tomography (SPECT) imaging
timeFrame: Through study completion. Estimated at one year
measure: A RP2D of MVT-5873/MVT-1075
timeFrame: Through study completion. Estimated at one year.
measure: Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2D
timeFrame: Through study completion. Estimated at one year.
measure: Evaluate duration of response of MVT-5873/MVT-1075
timeFrame: Through study completion. Estimated at one year.
measure: Evaluate formation of anti-drug antibodies (ADA)
timeFrame: On Day 1, Day 15 and End of Treatment Visit only of each cycle for up to 4 cycles. (each cycle is 57 days)
measure: Cmax
timeFrame: Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
measure: Cmin
timeFrame: Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
measure: Tmax
timeFrame: Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
measure: Vd
timeFrame: Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
measure: t1/2
timeFrame: Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
measure: AUC
timeFrame: Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
measure: Cl
timeFrame: Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
Other outcomes:
measure: Evaluate the relationship between circulating CA19-9 levels and tumor response
timeFrame: Through study completion. Estimated at one year.
measure: Evaluate the relationship between circulating CA19-9 levels and MVT-1075 pharmacokinetics
timeFrame: Through study completion. Estimated at one year.
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: New York
country: United States
facility: MSKCC
state: New York
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References:
citation: Tully KM, Tendler S, Carter LM, Sharma SK, Samuels ZV, Mandleywala K, Korsen JA, Delos Reyes AM, Piersigilli A, Travis WD, Sen T, Pillarsetty N, Poirier JT, Rudin CM, Lewis JS. Radioimmunotherapy Targeting Delta-like Ligand 3 in Small Cell Lung Cancer Exhibits Antitumor Efficacy with Low Toxicity. Clin Cancer Res. 2022 Apr 1;28(7):1391-1401. doi: 10.1158/1078-0432.CCR-21-1533.