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

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

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).

Study Overview

• Status: Terminated
• Conditions: Pancreatic Carcinoma; Tumors That Express CA 19-9
• Intervention / Treatment: Drug: MVT-1075; Drug: MVT-5873

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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • New York
    • New York, New York, United States, 10065
      • MSKCC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escalation Cohorts; MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose	Drug: MVT-1075; MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.; Other Names: 177Lu-CHX-A"-DTPA-HuMab-5B1; Drug: MVT-5873; MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.; Other Names: HuMab-5B1
Experimental: Expansion Cohort - no subjects enrolled; MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose	Drug: MVT-1075; MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.; Other Names: 177Lu-CHX-A"-DTPA-HuMab-5B1; Drug: MVT-5873; MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.; Other Names: HuMab-5B1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The MTD of MVT-5873/MVT-1075	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	Through study completion. Estimated at one year
Occurrence of graded adverse events (AEs) in each subject	Occurrence of graded AEs in each subject	Through study completion. Estimated at one year

Secondary Outcome Measures

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

Outcome Measure	Measure Description	Time Frame
Evaluate the relationship between circulating CA19-9 levels and tumor response	Periodic assessment of CA19-9 expression	Through study completion. Estimated at one year.
Evaluate the relationship between circulating CA19-9 levels and MVT-1075 pharmacokinetics	Periodic assessments pre and post MVT-1075	Through study completion. Estimated at one year.

Collaborators and Investigators

• Sponsor: BioNTech Research & Development, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): April 11, 2018
• Study Completion (Actual): April 11, 2018

Study Registration Dates

• First Submitted: March 23, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 19, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: CA19-9 Positive Malignancies
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: MV-0916-CP-001.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No