Clinical trial NCT05912244: A Study of IO102/IO103, Nivolumab, and Relatlimab in People With Melanoma
Official title: A Phase II Study of IO102/IO103 and Nivolumab-relatlimab Fixed Dose Combination in Untreated, Unresectable Stage III/IV Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Melanoma
Keywords: IO102/IO103
Nivolumab
Relatlimab
Unresectable
Stage III/IV
23-098
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: IO Biotech
First posted: 2023-06-22
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Sequentially in a single-arm, nonrandomized two-stage trial design
Primary purpose: TREATMENT

Brief summary: The researchers are doing this study to find out whether the study vaccines, IO102/IO103, given in combination with the standard-of-care drug combination, nivolumab and relatlimab, is a safe and effective treatment for people with untreated, unresectable melanoma.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years at the time of informed consent
2. Patient must be able to provide informed consent.
3. Patient must have a histologically confirmed diagnosis of locally advanced unresectable stage III or metastatic stage IV melanoma not amenable to local therapy.
4. Patient must have not received any prior systemic therapy directed against unresectable stage III or IV melanoma. Prior neoadjuvant and adjuvant ICIs and BRAF/MEK inhibitors are permitted as long as the last dose was \> 6 months prior to recurrence.
5. Patients must have at least one extraskeletal, extracranial measurable melanoma lesion as defined by RECIST v1.1. Note: A formal RECIST read by a study radiologist is not needed at the time of enrollment. Measurable disease can be assessed by the treating investigator.
6. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
7. Adequate laboratory function at screening, defined as:

   1. Hemoglobin ≥ 9.0 g/dL
   2. WBC ≥ 2000/uL
   3. Platelet count ≥ 100 × 10\^9 /L
   4. Serum direct bilirubin ≤ 1.5 × upper limit of normal (ULN); AST and ALT ≤ 2.5 × ULN. (Total bilirubin \< 3 mg/dL for subjects with Gilbert's disease)
   5. Calculated creatinine clearance (CrCl) ≥15 mL/min based on the Cockcroft-Gault equation
8. Patients of childbearing potential\* who are sexually activ partner must use two methods of effective contraception from screening, and must agree to continue using such precautions for 23 weeks after the final dose of investigational product: cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.

   \*Patients of childbearing potential are defined as those who are assigned female at birth and not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
9. Male patients who are sexually active with partners of childbearing potential must use highly effective methods of contraception throughout the study and for at least four months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period.

Exclusion Criteria:

1. Uveal melanoma
2. Untreated central nervous system (CNS) metastases or any leptomeningeal involvement. Asymptomatic brain metastases that have been treated with external radiotherapy are permitted.
3. Any immunotherapy treatment for unresectable stage III/IV melanoma or any other prior unresectable malignancy. Prior neoadjuvant and adjuvant ICIs and BRAF/MEK inhibitors are permitted as long as the last dose was \> 6 months prior to recurrence.
4. Systemic steroid therapy higher than physiologic dose steroid replacement (\>10 mg/day of prednisone or equivalent), given within 14 days of starting treatment, or other immunosuppressive medications within 14 days of the start of treatment. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. 5. Treatment with any live/attenuated vaccine within 30 days of first study treatment. Inactivated and mRNA vaccines are permitted.

6. History of motor neuropathy considered to be of autoimmune origin to be of autoimmune origin (e.g., Guillain-Barre syndrome, myasthenia gravis) 7. Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator 8. History of severe allergic reactions to any unknown allergens or any components of the study drugs.

9. Uncontrolled (i.e., unstable) concomitant medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety or compliance with the study procedures. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 10. Active hepatitis B virus (HBV) with a viral load \>100 IU/mL 11. Active hepatitis C virus (HCV) with a viral load \>100 IU/mL 12. Patients who are breastfeeding or who are pregnant as evidenced by a positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) performed within 14 days of the first dose of study drug.

13. Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific circumstances where local regulations permit, a person who has been imprisoned may be permitted to continue as a participant.) 14. Participants who are compulsorily detained for treatment of either a psychiatric or physical illness (e.g., transmissible infection)

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 3 years
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: up to 100 days after the last dose
measure: Progression-free survival (PFS)
timeFrame: 3 years
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Healthcare Alliance (Data Collection Only)
state: Connecticut
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (All Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Limited Protocol Activities)
state: New York
city: Allentown
country: United States
facility: Lehigh Valley Health Network (Data Collection Only)
state: Pennsylvania
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: James Smithy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kjeldsen JW, Lorentzen CL, Martinenaite E, Ellebaek E, Donia M, Holmstroem RB, Klausen TW, Madsen CO, Ahmed SM, Weis-Banke SE, Holmstrom MO, Hendel HW, Ehrnrooth E, Zocca MB, Pedersen AW, Andersen MH, Svane IM. A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Nat Med. 2021 Dec;27(12):2212-2223. doi: 10.1038/s41591-021-01544-x. Epub 2021 Dec 9.
citation: Lorentzen CL, Kjeldsen JW, Ehrnrooth E, Andersen MH, Marie Svane I. Long-term follow-up of anti-PD-1 naive patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. J Immunother Cancer. 2023 May;11(5):e006755. doi: 10.1136/jitc-2023-006755.