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

Pancreatic Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03118349
• Other study ID #: MV-0916-CP-001.01
• Status: Terminated
• Phase: Phase 1
• Start date: June 1, 2017
• Est. completion date: April 11, 2018

Study information

• Verified date: April 2023
• Source: BioNTech SE
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: April 11, 2018
• Est. primary completion date: April 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Carcinoma
• Pancreatic Neoplasms
• Tumors That Express CA 19-9

Intervention

Drug:
• MVT-1075
MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.
• MVT-5873
MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.

Locations

Country	Name	City	State
United States	MSKCC	New York	New York
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
BioNTech Research & Development, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate the relationship between circulating CA19-9 levels and tumor response	Periodic assessment of CA19-9 expression	Through study completion. Estimated at one year.
Other	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.
Primary	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
Primary	Occurrence of graded adverse events (AEs) in each subject	Occurrence of graded AEs in each subject	Through study completion. Estimated at one year
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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)
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).