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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 solid malignancy, non-hematological.
4. Participants must be under treatment with one of the following FDA-approved standard-of-care anti-PD-1 or anti-PD-L1 therapies: 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). Participants may be on additional FDA-approved immunotherapy treatments including anti-CTLA4 therapies or anti-LAG-3 therapies in addition to the anti-PD-1 or anti-PD-L1 backbone therapy. The specific additional therapies allowed are: Ipilimumab (Yervoy; anti-CTLA4 antibody), Tremelimumab (Imjudo; anti-CTLA4 antibody), or Relatlimab (Opdualag; anti-LAG-3).
5. Participants must have stable disease or concern for progression of their disease on most recent imaging scans yet be continuing on anti-PD1 or anti-PD-L1 therapy, per the treating physician. Participants may continue on anti-CTLA-4 or anti-LAG-3 ICIs if they have already been taking these when assessed to have stable or potentially progressive disease on most recent imaging. Subjects may also discontinue anti-CTLA-4 or anti-LAG-3 ICIs and remain eligible as long as they meet above criteria and continue the anti-PD-1 or anti-PD-L1 component of therapy that they have already been 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 who are not surgically or medically sterile must agree to use an acceptable method of contraception, 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 could impregnate their sexual partners must also 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. 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. The participant has adequate renal function as defined by Cockcroft-Gault calculated creatinine clearance \>40 ml/min
12. 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
13. 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
14. For phase 1a, participant must be willing to undergo 2 core needle biopsies that are accessible via ultrasound and/or clinical biopsy.
15. Adequate uptake of 86Y-NM600 (2x red bone marrow) on PET CT imaging.
16. No grade 2 toxicities that are new compared to baseline and lack a possible alternative explanation (e.g., underlying disease or another known cause) were noted by Day 7 after the 86Y-NM600 infusion. Toxicities with at least a possibly related attribution to disease and/or another cause-even if also considered at least possibly related to 86Y-NM600-are permitted.
17. No Grade ≥ 3 toxicities that are new compared to baseline were noted by day 7 after 86Y-NM600 infusion.

Exclusion Criteria:

1. Other concurrent severe and/or uncontrolled concomitant medical or psychiatric conditions (e.g., active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol, per investigator discretion.
2. The participant is taking strong inducers or inhibitors of CYP450 enzymes or drug transporters that cannot be held from at least 30 days prior to administration of 86Y-NM600 through the final 90Y-NM600 infusion without any expected adverse events. Examples include: clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, phenobarbital, phenytoin, rifampicin, and glucocorticoids.
3. Chemotherapy, radiotherapy, or major surgery within 3 weeks prior to study enrollment (this will be greater than 5 weeks prior to 90Y-NM600 therapy).

   a. For patients receiving prior radiation therapy, the dose to tumor, kidneys, liver, and bone marrow must be recorded, if available.
4. The participant is pregnant, breastfeeding, or expecting to conceive or could impregnate someone within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment.
5. Any ongoing or active infection, including active tuberculosis, hepatitis B or C, or known infection with the human immunodeficiency virus (HIV) that is not well controlled (undetectable viral load by PCR) by anti-retroviral therapy.
6. Concurrent treatment with any other systemic anti-cancer or investigational agents other than an anti-PD-1, anti-PD-L1, anti-CTLA-4, or anti-LAG-3 antibody. Subjects cannot be receiving concomitant chemotherapy, experimental therapy or any other therapy not otherwise outlined by the trial for the purposes of anti-cancer treatment.

   b. Palliative external beam radiation therapy may be delivered to patients during this study if deemed necessary and safe by the treating physician.

   c. Participants can be receiving dual immune checkpoint inhibition with an anti-CTLA-4 antibody or an anti-LAG-3 antibody in addition to an anti-PD-1 or anti-PD-L1 therapy.
7. Patients with a history of or concurrent second primary malignancy within 2 years to study enrollment are excluded, with the exception of patients who have had definitive treatment of a primary skin basal cell, skin squamous cell carcinomas, or localized low or intermediate risk prostate cancer - these subjects are eligible 3 months after completion of definitive treatment for that prior cancer.
8. Participants that have had total body or hemibody irradiation, or have had prior systemic radioisotope therapy (except for benign thyroid disease)
9. Any condition requiring the use of immunosuppression, excluding rheumatologic conditions or endocrine conditions treated with stable doses of corticosteroids (equivalent to prednisone 10 mg daily)
10. Ongoing hemodialysis or peritoneal dialysis
11. Any known medical condition that predisposes the subject to uncontrolled bleeding such as hemophilia or clotting factor deficiencies
12. Participants with known genetic conditions causing pre-disposition to RT toxicity (i.e.: Li-Fraumeni, ataxia telangiectasia mutated (ATM) deficiency, active scleroderma, active inflammatory bowel disease, active systemic lupus)
13. Patients with an implanted defibrillator or with an implanted pacemaker and pacemaker dependency for rate or rhythm control
14. Patients with repeated demonstration on two EKGs of a QTcF interval greater than 470 milliseconds or use of medications known to prolong the QT/QTc interval
15. Participants who cannot provide independent, legal, informed consent

• Madison, Wisconsin, United States