Y-NM600 in Patients Receiving Anti-PD-1 or Anti-PD-L1 for Metastatic Cancer

Inclusion Criteria

• •1. Participant must be informed of the investigational nature of the study and must be able to sign a written informed consent.
• •2. Participants with histologically or cytologically confirmed squamous cell carcinoma thought to originate from the head and neck region (HNC).
• •3. Participants must have metastatic disease of one of the following types: bile duct cancer, bladder cancer, cervical cancer, colorectal cancer, cutaneous squamous cell cancer, esophageal cancer, head and neck squamous cell carcinoma, kidney cancer, liver cancer, lung cancer, melanoma, merkel cell carcinoma, mesothelioma, stomach cancer, triple-negative breast cancer, or any solid cancer with mismatch repair deficiency.
• •4. Participants must be under treatment with one of the following standard-of-care anti-PD-1 or anti-PD-L1 therapies that is FDA approved for the patient's specific type of metastatic cancer: Pembrolizumab (Keytruda; anti-PD-1 antibody), Nivolumab (Opdivo; anti-PD-1 antibody), Atezolizumab (Tecentriq, anti-PD-L1 antibody), Avelumab (Bavencio; anti-PD-L1 antibody), Durvalumab (Imfinzi; anti-PD-L1 antibody), Cemiplimab (Libtayo; anti-PD-1 antibody), Dostarlimab (Jemperli; anti-PD-1 antibody). The patient must also have iUPD (Immune Unconfirmed Progressive Disease) after most recent imaging studies and be eligible to continue anti-PD-1 or anti-PD-L1 therapy, per the treating physician.
• •1. For the purposes of this study, patients will be considered to have iUPD if they have been on treatment with anti-PD-1 or anti-PD-L1 therapy for any duration of time and, on their most recent standard-of-care imaging, been observed to have evidence of progression when the most recent scans prior to those did not show evidence of progression. Evidence of progression in this context will be defined as a 20 percent or greater increase in the sum of diameters of up to 5 lesions (these lesions will be identified as representative of the distribution of the patient's metastatic disease by the treating physician), the appearance of a new lesion, or the unequivocal progression of any lesion.
• •2. Participants with iUPD standardly continue on anti-PD-1 or anti-PD-L1 therapy if the treating physician determines they do not have worsening performance status, clinically relevant increase in disease-related symptoms, or requirement of intensified management of disease-related symptoms. To be eligible for study, a participant's treating physician must determine that it is in the patient's best interest to continue on their current immune checkpoint inhibition regimen for additional treatment cycles until the subject's next scheduled standard-of-care imaging assessment. Treating physicians making this decision should generally do so if they feel the subject has no available better alternative treatment approach.
• •3. In addition to anti-PD-1 or anti-PD-L1 therapy, patients may also be under treatment with and may continue to receive Ipilimumab (Yervoy; anti-CTLA4 antibody) or Tremelimumab (Imjuno; anti-CTLA4 antibody) during this study. However, participants must have been found to have iUPD while on the immune checkpoint therapy regimen that they receive during this study (i.e., participant's treating physician must determine that it is in the participant's best interest to stay on the current regimen of immune checkpoint inhibition until the subject's next standard of care imaging evaluation).
• •5. Participants must have received and shown evidence of progression or iUPD on at least one front-line therapy for metastatic disease. This can include the immune checkpoint inhibitor they are currently taking.
• •6. Participants must have at least one evaluable (measurable) tumor that is radiographically detectable.
• •7. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
• •8. Participants must have a life expectancy of at least 6 months.
• •9. People who could become pregnant have a confirmed negative urine pregnancy test within 7 days prior to receiving Y-NM600.
• •10. Participants must use a medically acceptable method of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for 6 months after last dose of study drug. Participants who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be people who could become pregnant.
• •11. Participants who are not surgically or medically sterile agree to use an acceptable method of contraception. Participants who could impregnate their sexual partners must abstain from intercourse for three weeks after Y-NM600 treatment and agree to use condoms at least 2 months after the last dose of this drug. Total abstinence for the same study period is an acceptable alternative.
• •12. The participant has adequate renal function as defined by Cockcroft-Gault calculated creatinine clearance \>60 ml/min
• •13. The subject has adequate hepatic function as defined by:
• •1. total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• •2. aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3.0 times the ULN
• •14. The participant has adequate hematologic function without Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) injection or transfusion in the prior 7 days, as evidenced by:
• •1. an absolute neutrophil count (ANC) greater than or equal to 2000 / μL
• •2. hemoglobin greater than or equal to 8 g/dL
• •3. platelets greater than or equal to 100,000 / μL, or, if full-dose anticoagulation therapy is used, platelets greater than or equal to 150,000 / μL are required.
• •4. lymphocytes greater than or equal to 1000 / μL
• •15. For phase 1a, participant must be willing to undergo 2 core needle biopsies that are accessible via ultrasound and/or clinical biopsy.
• •16. Adequate uptake of 86Y-NM600 (3x red bone marrow) on PET CT imaging as determined by Nuclear Medicine.
• •17. No grade 2 toxicities new compared to baseline and unrelated or unlikely related to disease or any known cause other than 86Y-NM600 were noted through day 7 after 86Y-NM600 infusion.
• •18. No grade greater than or equal to 3 toxicities new compared to baseline were noted through day 7 after 86Y-NM600 infusion.