Study of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy

Phase 1

Terminated

• Conditions: Tumors That Express CA 19-9; Pancreatic Carcinoma
• Interventions: Drug: MVT-1075; Drug: MVT-5873

• Registration Number: NCT03118349
• Lead Sponsor: BioNTech Research & Development, Inc.

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.

Study Timeline

• Study First Submitted: 2017-03-23
• Study First Submitted QC: 2017-04-13
• Study First Posted: 2017-04-18
• Study Start: 2017-06-01
• Primary Completion: 2018-04-11
• Study Completion: 2018-04-11
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-19
• Last Update Posted: 2023-04-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Escalation Cohorts	MVT-1075	MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose
Expansion Cohort - no subjects enrolled	MVT-1075	MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose
Escalation Cohorts	MVT-5873	MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose
Expansion Cohort - no subjects enrolled	MVT-5873	MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose

Primary Outcome Measures

Name	Time	Method
Occurrence of graded adverse events (AEs) in each subject	Through study completion. Estimated at one year	Occurrence of graded AEs in each subject
The MTD of MVT-5873/MVT-1075	Through study completion. Estimated at one year	The MTD of MVT-5873/MVT-1075 is the highest dose of MVT-1075 at which fewer than 33% subjects experience a dose limiting toxicity

Secondary Outcome Measures

Name	Time	Method
Specific organ distribution of MVT-1075 as assessed with planar gamma camera	Through study completion. Estimated at one year	Specific organ distribution of MVT-1075 as assessed with planar gamma camera
Specific organ distribution of MVT-1075 as assessed with single-photon emission computed tomography (SPECT) imaging	Through study completion. Estimated at one year	Specific organ distribution of MVT-1075 as assessed with SPECT imaging
A RP2D of MVT-5873/MVT-1075	Through study completion. Estimated at one year.	Previously determined MTD; Overall assessment of safety as determined by Safety Committee
Cmax	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).	The peak plasma concentration of the drug after administration
Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2D	Through study completion. Estimated at one year.	Response categories as assessed by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
Evaluate duration of response of MVT-5873/MVT-1075	Through study completion. Estimated at one year.	Time from first onset of response to progression or death
Cmin	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 the lowest concentration that the drug reaches before the next dose is administered.
Vd	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).	Volume of distribution
t1/2	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).	Half-life of Elimination
Evaluate formation of anti-drug antibodies (ADA)	On Day 1, Day 15 and End of Treatment Visit only of each cycle for up to 4 cycles. (each cycle is 57 days)	Presence or absence of ADA as assessed by assay to be developed
Tmax	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).	Time to reach the study drug
AUC	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).	Area under the plasma concentration time curve
Cl	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).	Clearance of study drug

Trial Locations

Locations (2)

MSKCC; 🇺🇸 New York, New York, United States

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States