Safety of RAD301 in Healthy Human Volunteers and Patients With Pancreatic Cancer

This is a Phase 1a, open label, single dose, extended study of safety and biokinetics of RAD301 in healthy human volunteers and individuals with PDAC.

This will be a Phase 1a, open label, single dose, extended study of safety and biokinetics of RAD301 in healthy human volunteers and individuals with PDAC. The procedures will be similar in both groups, but there could be more scans in healthy volunteers and fewer in individuals with PDAC during the same time interval if individuals are intolerant of lying still on an imaging table for long periods of time. All individuals will have vital signs, ECGs, and blood for safety assessments collected before and 2 weeks after a single dose, intravenous (IV) administration of the investigational radiopharmaceutical, RAD301, at a dose of 150 ± 50 MBq (\~ 4 mCi). There will be 3 whole body (WB) PET-CT and PET scanning sessions.

The initial WB acquisition should take approximately 10 minutes. A subsequent WB PET-only scan will be performed approximately 45 minutes after the injection. As time passes and less radioactivity is localizable to the distal extremities, the scan length may be decreased from vertex-to-thighs. The duration of each scan may increase to partially compensate for radioactive decay. More than one WB scan may be performed in healthy volunteers during the first imaging session, but only one scan will be required in individuals with PDAC who are not able to tolerate additional scans. The entire first imaging session will last up to approximately 2 hours. The individuals will then be given a rest period (lunch break) after which the sequence of imaging scans could be repeated.

This second imaging session (WB PET only) will be optional and depends on the robustness of the individual and the availability of the clinical scanner. The second imaging session will take place mid-day, after the break, and will last up to 1.5 hours.

There will be a third, or final imaging session (WB PET only) at the end of the day for all participants, which will strive to include the time interval after approximately 4 physical half-lives of Gallium-68 (Ga-68). The third imaging session will last up to 1.5 hours.

Eligibility Criteria:
Inclusion Criteria:

1. Must be ≥ 18 years of age at the time of signing the informed consent.
2. All participants must be willing and able to give written informed consent.
3. For patients with PDAC: have a history of histologically or cytologically confirmed PDAC and have had a SOC CT or MRI within 8 weeks prior to signing consent that indicates the presence of at least 1 site of new or residual disease.
4. Screening laboratory values within 30 days prior to administration of the study drug:

   1. WBC ≥ 1200/μL
   2. ANC ≥ 1000/μL
   3. Platelets ≥ 75,000/μL
   4. Hemoglobin ≥ 9.0 g/dL
   5. Creatinine ≤ 1.5 mg/dL
   6. AST/ALT ≤ 3 x ULN for patients with no liver metastases.
   7. AST/ALT ≤ 5 x ULN for patients with liver metastases.
   8. Bilirubin ≤ 1.5 mg/dL except for participants with Gilbert's disease.
5. Patients should have a life expectancy of ≥ 12 weeks as judged by the Investigator.
6. All participants must have baseline pulse oximetry ≥ 95% on room air.
7. Unremarkable ECGs, with PR intervals of less than 200 msec and QTcF intervals (corrected with Frederica's method) of less than 450 msec.
8. Willing to refrain from taking illicit drugs one week prior to PET scanning and for the next 4 weeks after administration of RAD301.
9. Willing to refrain from donating blood for 4 weeks after administration of RAD301.
10. Have not participated in any other research study that requires taking medication for 4 weeks (or 10 half-lives, whichever is longer) prior to study drug administration and for 4 weeks after study drug administration.

Exclusion Criteria:

1. Participant may not be a member of a vulnerable population defined as participants who are not able to understand the nature of the trial and provide informed consent or who have any medical, psychological or sociological condition that in the opinion of the investigator would interfere with the ability to give consent or interfere with protocol compliance.
2. Women may not be pregnant or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test within 72 hours prior to administration of RAD301.
3. History suggestive of atopia, as indicated by allergies to multiple medications, or foods.
4. History, physical examination, or clinical laboratory tests suggestive of a condition, disorder, or disease that could adversely affect drug absorption, distribution, metabolism, or elimination of RAD301, including chronic liver or renal failure.
5. Unable to tolerate the study procedures.
6. Patients with brain metastases are eligible as long as there is no requirement for high doses of systemic corticosteroids that could result in immunosuppression (\>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. An MRI is not required to rule out brain metastases or leptomeningeal metastases
7. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, or interfere with the interpretation of study results.
8. Clinically significant cardiovascular/ cerebrovascular disease defined as cerebral vascular accident, stroke, carotid artery disease transient ischemic attach (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class \>II) or serious cardiac arrhythmia.
9. Other than PDAC, a prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast.
10. Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
11. Participants who underwent major surgery within 4 weeks of enrollment (not including diagnostic laparoscopy).