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

NCT03118349 | Terminated Phase 1 FDA Drug

• 1 other identifier: MV-0916-CP-001.01
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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).

Conditions

Pancreatic Carcinoma; Tumors That Express CA 19-9

Keywords

CA19-9 Positive Malignancies

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (13)

• 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 single-photon emission computed tomography (SPECT) imaging

  Through study completion. Estimated at one year

• A RP2D of MVT-5873/MVT-1075

  Through study completion. Estimated at one year.

• Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2D

  Through study completion. Estimated at one year.

• Evaluate duration of response of MVT-5873/MVT-1075

  Through study completion. Estimated at one year.

Other Outcomes (2)

• Evaluate the relationship between circulating CA19-9 levels and tumor response

  Through study completion. Estimated at one year.

• Evaluate the relationship between circulating CA19-9 levels and MVT-1075 pharmacokinetics

  Through study completion. Estimated at one year.

Study Arms (2)

Escalation Cohorts

EXPERIMENTAL

MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose

Drug: MVT-1075; Drug: MVT-5873

Expansion Cohort - no subjects enrolled

EXPERIMENTAL

MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose

Drug: MVT-1075; Drug: MVT-5873

Interventions

MVT-1075 DRUG

MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.

Also known as: 177Lu-CHX-A"-DTPA-HuMab-5B1

Escalation Cohorts; Expansion Cohort - no subjects enrolled

MVT-5873 DRUG

MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.

Also known as: HuMab-5B1

Escalation Cohorts; Expansion Cohort - no subjects enrolled

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, informed consent
• Age 18 or more years
• Histologically or cytologically confirmed, previously treated, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies
• Prior treatment with (or intolerance to) at least one standard systemic regimen for the patient's respective tumor
• 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
• Evaluable or measurable disease based on RECIST 1.1
• 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
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or Karnofsky performance status (KPS) of 100% to 80%
• Adequate hematologic, renal and hepatic laboratory parameters
• Willingness to participate in collection of pharmacokinetic samples
• 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)

You may not qualify if:

• Brain metastases unless previously treated and well controlled for at least 3 months
• Any tumor mass greater than 10 cm in longest diameter
• Other known active cancer(s) likely to require treatment in the next two years
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• Prior radiation therapy encompassing more than 25% of the skeleton or prior treatment with 89Strontium or 153Samarium
• Fewer than 28 days from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation except for:
• Ongoing hormonal therapy administered for control of cancer (e.g., breast cancer, prostate cancer), which may be continued throughout the study
• MVT-5873 and MVT-2163 administered as part of a different protocol
• Major surgery other than diagnostic surgery within 28 days of Study Day 1
• History of anaphylactic reaction to human, or humanized, antibody
• Pregnant or currently breast-feeding
• Known to be positive for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
• Psychiatric illness/social situations that would interfere with compliance with study requirements
• Significant cardiovascular risk including, but not limited to, recent (within 4 weeks) coronary stenting or myocardial infarction within 6 months

Sponsors & Collaborators

• BioNTech Research & Development, Inc.: lead

Study Sites (2)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

MSKCC

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 35046060 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 18, 2017
• Study Start: June 1, 2017
• Primary Completion: April 11, 2018
• Study Completion: April 11, 2018
• Last Updated: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)