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

NCT07197671 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: 2025-0647SMPH/HUMAN ONCOLOGY/HUMAN ONCOProtocol Version 10/31/25UW24136P50CA278595-06A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Participants with metastatic cancer who are taking anti-PD-1 or anti-PD-L1 therapy will be enrolled to assess the safety of and find the optimal dose for radioactive imaging agents and to explore whether these agents will make current drug therapies work better. Up to 60 participants will be enrolled and can expect to be on study for up to 9 months.

Conditions

Metastatic Cancer

Outcome Measures

Primary Outcomes (2)

• Toxicities greater than or equal to Grade 3 at least possibly related to 86Y-NM600

  Toxicities greater than or equal to Grade 3 at least possibly related to 86Y-NM600 by day 7 (greater than 10 half-lives of 86Y) after 86Y-NM600 injection, as defined by the NCI CTCAE version 5.0.

  baseline screening, Day 7 after 86Y-NM600 injection

• Toxicities greater than or equal to Grade 3 at least possibly related to 90Y-NM600

  Toxicities greater than or equal to Grade 3 at least possibly related to 90Y-NM600 by day 42 after final 90Y-NM600 injection, as defined by the NCI CTCAE version 5.0. Time points of investigation include: * baseline screening * Phase 1A: post injection week 1, week 2, week 3, week 4 * Phase 1B: 7 days after each injection, 30 days and 42 days after final injection

  up to 9 months on study

Secondary Outcomes (7)

• Pharmacokinetics of Y-NM600: Blood concentration verse time curve

  3-5 min after end of infusion, 0.5 hours, *2.0 hours, 4.0 hours, 24 hour, and *48 hours after infusion (*Phase 1A only)

• Pharmacokinetics of Y-NM600: Time to reach maximum concentration of Y-NM600 in Blood

  Blood draws at estimated Cmax 3-5 min after end of infusion, 0.5 hours, *2.0 hours, 4.0 hours, 24 hour, and *48 hours after infusion (*Phase 1A only)

• Pharmacokinetics of Y-NM600: Blood Radioactivity from Y-NM600

  Blood draws at estimated Cmax 3-5 min after end of infusion, 0.5 hours, *2.0 hours, 4.0 hours, 24 hours, and *48 hours after infusion (*Phase 1A only)

• Pharmacokinetics of Y-NM600: Physiological Half-life of Y-NM600

  Blood draws at estimated Cmax 3-5 min after end of infusion, 0.5 hours, *2.0 hours, 4.0 hours, 24 hours, and *48 hours after infusion (*Phase 1A only)

• Proportion of Participants with 3-fold or greater uptake of 86Y-NM600 in tumor site compared to red bone marrow

  48-72 hours after 86Y-NM600 infusion

Other Outcomes (13)

• Progression Free Survival (PFS)

  Day 1 of treatment, Standard-of-care imaging follow-up ~3 and 6 months after Day 1, Time of disease progression (monitored up to 5 years)

• Overall Survival (OS)

  Day 1 of treatment, Standard-of-care imaging follow-up ~3 and 6 months after Day 1, Time of disease progression, Death (monitored up to 5 years)

• Duration of Response

  Day 1 of treatment, Standard-of-care imaging follow-up ~3 and 6 months after Day 1, Time of disease progression (monitored up to 5 years)

Study Arms (7)

Phase 1A: Dose Level -1

EXPERIMENTAL

20 mCi x 1 90Y-NM600

Drug: 90Y-NM600

Phase 1A: Dose Level 1

EXPERIMENTAL

35 mCi x 1 90Y-NM600

Drug: 90Y-NM600

Phase 1A: Dose Level 2

EXPERIMENTAL

70 mCi x 1 90Y-NM600

Drug: 90Y-NM600

Phase 1A: Dose Level 3

EXPERIMENTAL

105 mCi x 1 90Y-NM600

Drug: 90Y-NM600

Phase 1A: Dose Level 4

EXPERIMENTAL

140 mCi x 1 90Y-NM600

Drug: 90Y-NM600

Phase 1B: Single Dose

EXPERIMENTAL

Informed by Phase 1A

Drug: 90Y-NM600

Phase 1B: Multi-dose

EXPERIMENTAL

Informed by Phase 1A and Single Dose Phase 1B

Drug: 90Y-NM600

Interventions

90Y-NM600 DRUG

NM600 is a tumor-selective, pan-cancer, targeted radionuclide therapy (TRT) with theranostic capacity

Also known as: alkylphosphocholine (APCh) analog

Phase 1A: Dose Level -1; Phase 1A: Dose Level 1; Phase 1A: Dose Level 2; Phase 1A: Dose Level 3; Phase 1A: Dose Level 4; Phase 1B: Multi-dose; Phase 1B: Single Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be informed of the investigational nature of the study and must be able to sign a written informed consent.
• Participants with histologically or cytologically confirmed squamous cell carcinoma thought to originate from the head and neck region (HNC).
• 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.
• 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.
• 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.
• 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.
• 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).
• 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.
• Participants must have at least one evaluable (measurable) tumor that is radiographically detectable.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
• Participants must have a life expectancy of at least 6 months.
• People who could become pregnant have a confirmed negative urine pregnancy test within 7 days prior to receiving Y-NM600.
• 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.
• 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.
• The participant has adequate renal function as defined by Cockcroft-Gault calculated creatinine clearance \>60 ml/min

You may not qualify if:

• 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.
• 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.
• 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.
• 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.
• 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.
• Concurrent treatment with any other systemic anti-cancer or investigational agents other than an anti-PD-1, anti-PD-L1, or anti-CTLA-4 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 in addition to an anti-PD-1 or anti-PD-L1 therapy.
• 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.
• Participants that have had total body or hemibody irradiation, or have had prior systemic radioisotope therapy (except for benign thyroid disease)
• 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)
• Ongoing hemodialysis or peritoneal dialysis
• Any known medical condition that predisposes the subject to uncontrolled bleeding such as hemophilia or clotting factor deficiencies
• 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)

Sponsors & Collaborators

• Archeus Technologies, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• University of Wisconsin, Madison: lead

Study Sites (1)

UW Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Grace Blitzer, MD

  UW Carbone Cancer Center

  PRINCIPAL INVESTIGATOR

• Justine Bruce, MD

  UW Carbone Cancer Center

  PRINCIPAL INVESTIGATOR

• Zachary Morris, PhD

  UW Carbone Cancer Center

  STUDY CHAIR

• Paul Harari, MD

  UW Carbone Cancer Center

  STUDY CHAIR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3x3 dose escalation

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: September 29, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (1)