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

ConditionMetastatic Cancer

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity of Wisconsin, Madison

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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 solid malignancy, non-hematological.

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).

Disqualifiers

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).

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.

Trial design

Design model

Sequential

Treatments tested in this trial

90Y-NM600
Drug
NM600 is a tumor-selective, pan-cancer, targeted radionuclide therapy (TRT) with theranostic capacity

Treatment groups

60 Participants

are divided into 7 treatment groups

Treatment groups

See each treatment group below.

Group A: Phase 1A: Dose Level -1Experimental treatment 1 intervention

Group B: Phase 1A: Dose Level 1Experimental treatment 1 intervention

Group C: Phase 1A: Dose Level 2Experimental treatment 1 intervention

Group D: Phase 1A: Dose Level 3Experimental treatment 1 intervention

Group E: Phase 1A: Dose Level 4Experimental treatment 1 intervention

Group F: Phase 1B: Single DoseExperimental treatment 1 intervention

Group G: Phase 1B: Multi-doseExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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

Time frame

up to 9 months on study

Secondary outcomes

Pharmacokinetics of Y-NM600: Blood concentration verse time curve

Blood concentration verse time curve, 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)

Time frame

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)

Time frame

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 hour, and \*48 hours after infusion (\*Phase 1A only)

Time frame

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

Phase 1a: Blood draws at estimated Cmax 3-5 min after end of infusion (+/- 5 min), 0.5 hours (+/- 15 min), 2.0 hours (+/- 30 min), 4.0 hours (+/- 30 min), 24 hours (+/- 120 min), and 48 hours (+/- 120 min) after infusion. Phase 1b: Blood draws at estimated Cmax 3-5 min after end of infusion (+/- 5 min), 0.5 hours (+/- 15 min), 4.0 hours (+/- 30 min), and 24 hours (+/- 120 min) after infusion. Cumulative urine collection will be done for 6 hours with specific samples collected and pooled at 0.5 hours (+/- 15 min), 3 hours (+/- 30 min), and at 5 hours (+/- 30 min) after infusion.

Time frame

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)

Other outcomes

Progression Free Survival (PFS)

PFS is defined as the time from Day 1 of treatment until the criteria for disease progression is met as defined by iRECIST or death as a result of any cause.

Time frame

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)

OS is defined as time from Day 1 of treatment until death as a result of any cause.

Time frame

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

Duration of response is the period measured from the time that measurement criteria are met for immune complete response (iCR), immune partial response (iPR), or immune-related stable disease (iSD) (whichever status is recorded first) until the date that recurrent or iPD is objectively documented.

Time frame

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)

EORTC QLQ-C30

Determine the impact of 90Y-NM600 on patient-reported health-related quality of life (HRQoL) by assessing the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The EORTC QLQ-C30 is scored from 0-100 where higher scores indicate a better quality of life.

Time frame

baseline, 1 week after Day 1, 12 weeks after Day 1

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Wisconsin, Madison

Lead sponsor

Archeus Technologies, Inc.

Collaborator

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov

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