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

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

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

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 IHC performed on tumor samples or
elevated serum levels (≥1.5 x ULN) of CA19-9 considered secondary to tumor

6. Evaluable or measurable disease based on RECIST 1.1 (50)

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 Table 2

9. ECOG performance status of 0 or 1 (51), or KPS of 100% to 80% (52)

10. Adequate hematologic, renal and hepatic laboratory parameters

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 (2) years

4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic
therapy

5. 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

6. Major surgery other than diagnostic surgery within 28 days of Study Day 1

7. History of anaphylactic reaction to human, or humanized, antibody

8. Pregnant or currently breast-feeding

9. Known to be positive for HIV, Hepatitis B, or Hepatitis C

10. Psychiatric illness/social situations that would interfere with compliance with study
requirements

11. Significant cardiovascular risk including, but not limited to, recent (within 4 weeks)
coronary stenting or myocardial infarction within 6 months