A Phase 2, Open-Label, Multicenter, Cohort Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma - ARTISTRY-6

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mural Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Apr 2022 → 15 Apr 2025

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Mural Oncology, Inc., US

External identifiers

EU CT number

2024-513229-22-00

EudraCT number

2021-001557-31

ClinicalTrials.gov

NCT04830124

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacokinetic, Dose response, Others, Pharmacodynamic, Safety

To evaluate the antitumor activity of nemvaleukin as monotherapy or
in combination with pembrolizumab by assessment of overall response
rate (ORR).

Secondary objectives 2

1. To evaluate the antitumor activity of nemvaleukin as monotherapy or in combination with pembrolizumab (other than by ORR)
2. To evaluate the safety and tolerability of nemvaleukin as monotherapy or in combination with pembrolizumab.

Conditions and MedDRA coding

Advanced cutaneous melanoma and Advanced mucosal melanoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patient is >=18 years of age.
2. Patient or patient's legal representative is willing and able to provide written informed consent
3. Patient is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
4. The patient must have one of the following: • Cohort 1 (ACM with SC dosing): To have unresectable and/or metastatic cutaneous melanoma. No more than 5 patients with acral melanoma may enroll in this cohort • Cohort 2 (AMM with IV dosing): To have unresectable and/or metastatic mucosal melanoma • Cohort 3 (ACM with less frequent IV dosing): To have unresectable and/or metastatic cutaneous melanoma. No patients with mucosal or acral melanoma may enroll in this cohort. • Cohort 4 (advanced cutaneous melanoma with less frequent IV nemvaleukin dosing in combination with pembrolizumab): Patient has unresectable and/or metastatic cutaneous melanoma. No patients with mucosal or acral melanoma may enroll in this cohort.
5. Patients who have received the following prior therapies: • Cohorts 1 and 2 - Patients who have received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy, and ≤1 other prior regimen of systemic anti-neoplastic therapy (eg, targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy counts as 1 prior regimen. Patients must have experienced objective response (PR or CR by RECIST 1.1 or iRECIST) or stable disease (by RECIST 1.1 or iRECIST) as BOR to anti-PD‑[L]1 therapy. Patients with confirmed progressive disease (by RECIST 1.1 or iRECIST) as best response may be included, if they received anti PD [L]1 therapy for ≥12 weeks (from first dose to last dose). Patients with BRAF mutations may or may not have received prior targeted therapy. • Cohort 3 - Patients who have received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy or anti-lymphocyte-activation gene 3 (LAG- 3) therapy, and ≤1 other prior regimen of systemic anti-neoplastic therapy (eg, targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy counts as 1 prior regimen. Patients must have experienced objective response (PR or CR by RECIST 1.1 or iRECIST) or stable disease (by RECIST 1.1 or iRECIST) as BOR to anti PD‑[L]1 therapy. Patients with confirmed progressive disease (by RECIST 1.1 or iRECIST) as best response may be included, if they received anti-PD-[L]1 therapy for ≥12 weeks (from first dose to last dose). Patients with BRAF mutations may or may not have received prior targeted therapy. • Cohort 4 - Patients must not have received prior systemic anticancer therapy for unresectable or metastatic melanoma. Prior adjuvant and/or neoadjuvant PD-[L]1 treatments are allowed if there is at least 6 months between the last dose and date of recurrence.
6. Cohorts 1, 2, and 3 - Patients who have received prior treatment with talimogene laherparepvec (TVEC) are allowed to enroll provided that last exposure to TVEC was ≥28 days prior to first exposure to nemvaleukin and that all injection-site reactions to TVEC have resolved. TVEC shall not be considered a prior regimen of systemic anti-neoplastic therapy, nor shall it be considered a systemic immunomodulatory agent.
7. Patient has at least one measurable lesion that qualifies as a target lesion based on RECIST 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
8. Cohort 1 and Cohort 2 (required); Cohort 3 (optional but recommended if lesions are accessible) and Cohort 4 (may be required for Inclusion 18, otherwise optional but recommended if the lesions are accessible): Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue. To qualify, archival tissue must have been sampled after last exposure to any systemic anti-neoplastic agent (including TVEC or anti-PD-L1 therapy whichever is last). Patients in Cohort 1 and Cohort 2 who are unable to undergo a biopsy may be enrolled if risk/benefit ratio of biopsy is considered unfavorable and/or when a biopsy would likely lead to significant delays in care. This decision must be accompanied by supporting documentation from the Investigator and performed in consultation with Medical Monitor. All pretreatment tissue must have been collected no more than 120 days prior to screening.
9. Patient has recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (ie, residual toxicity no worse than Grade 1 [Grade 2 treatment-associated peripheral neuropathy and/or any grade of alopecia are acceptable assuming all other inclusion criteria are met]). For immune-related adverse events (AEs) see Exclusion 21

Exclusion criteria 15

1. Patient has uveal melanoma (all cohorts), acral melanoma (Cohort 2, Cohort 3, and Cohort 4), or mucosal melanoma (Cohort 3 and Cohort 4).
2. Patient has received prior interleukin (IL)-2–based or IL-15–based cytokine therapy; patient has had exposure, including intralesional, to IL-12 or analogs thereof
3. Patient has received radiotherapy within the last 4 weeks before start of study treatment, with the exception of limited field palliative radiotherapy to an area not inclusive of or adjacent to the target lesion(s), that has been completed at least 2 weeks before starting study treatment with no ongoing acute sequelae (eg, radiation burns).
4. Patient requires systemic corticosteroids (>10 mg of prednisone daily, or equivalent) or patient has taken systemic corticosteroids (>10 mg of prednisone daily, or equivalent) within 14 days prior to the first dose of study drug; however, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted.
5. Patient has taken non-steroid systemic immunomodulatory agents (eg, Enbrel®, Humira®, etc) within 28 days prior to the first dose of study drug or anticipates use of these therapies during the study period.
6. Patient has undergone prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant.
7. Patient has received a live or live-attenuated vaccine(s) within 30 days prior to the first dose of study treatment. Note: COVID-19 vaccine is allowed (see Section 8.4.2 for further details).
8. Patient has received more than 3 doses of therapeutic systemic broadspectrum antibiotics within 4 days prior to the first dose of study drug. Antibiotics given for peri-procedural prophylaxis or given presumptively for a limited time (eg, until infection was ruled out), as well as topical or intra-ocular antibiotics, shall not be exclusionary.
9. Patient has had any active infection and/or a fever ≥38.5°C (≥101°F) within 3 days prior to the first dose of study drug.
10. Patient has active autoimmune disease(s) requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that has required chronic or frequent systemic steroids. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
11. Patient has underlying chronic lung disease, chronic obstructive pulmonary disease, metastatic lung disease, pleural effusions or other lung disorders (eg, pulmonary embolism) with a baseline room air oxygen saturation of <92% at screening, and/or dyspnea (≥Grade 3), which requires oxygen therapy.
12. Patient has any other concurrent uncontrolled illness, including mental illness or substance use, which may interfere with the ability of the patient to cooperate and participate in the study. Other examples of such conditions would include unstable, poorly controlled, or severe hypertension; clinically significant pericardial effusion; New York Heart Association Class III or Class IV congestive heart failure (see Appendix 1); high risk cardiovascular disease, defined as unstable angina, myocardial infarction, or cerebrovascular accident within 6 months of first dose; uncontrolled diabetes mellitus that has required 2 or more hospitalizations in the last year and/or emergent management within the last 6 months; severe peripheral vascular disease; or recent serious trauma.
13. Patient has had an active second malignancy within the previous 2 years. This criterion does not apply to patients with adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, prostate cancer of highest Gleason score ≤6 with undetectable prostatespecific antigen over the previous 12 months, urothelial carcinoma in situ, or ductal carcinoma in situ of the breast that has undergone full surgical resection.
14. Patient is currently pregnant, breastfeeding, or is planning to become pregnant or to begin breastfeeding during the study period or within 30 days (Cohort 1, Cohort 2, and Cohort 3) or 120 days (Cohort 4) after last study drug administration.
15. Patient has active or symptomatic central nervous system (CNS) metastases unless all the following have been met: such metastases have been treated by surgery and/or radiation therapy, and/or gamma knife and have remained radiographically stable (or shrinking) on 2 consecutive imaging examinations performed at least 6 weeks apart; AND steroids have been tapered to a dose of 10 mg of prednisone (or equivalent) or less for at least 2 weeks prior to first dose of study agent(s); AND the patient is neurologically stable. Patients with history of brain metastases or a suspicion of brain metastases must have a brain magnetic resonance imaging at baseline (Screening Visit).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Centrally-assessed overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohorts 1 and 2)
2. Investigator-assessed ORR based on RECIST 1.1 (Cohort 3) and Cohort 4

Secondary endpoints 3

1. Centrally-assessed duration of response (DOR), progression-free survival (PFS), and disease control rate (DCR), and time to response (TTR) based on RECIST 1.1.(Cohorts 1 and 2).
2. Investigator-assessed DOR, PFS, DCR, and TTR based on RECIST 1.1(Cohort 3 and Cohort 4)
3. Safety and tolerability will be assessed on the basis of treatmentemergent adverse events (TEAEs), vital signs and weight, electrocardiograms (ECGs), and clinical laboratory parameters.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mural Oncology Inc.

Sponsor organisation

Mural Oncology Inc.

Address

852 Winter Street

City

Waltham

Postcode

02451-1439

Country

United States

Scientific contact point

Organisation

Mural Oncology Inc.

Contact name

Mural Oncology, Inc.

Public contact point

Organisation

Mural Oncology Inc.

Contact name

Mural Oncology, Inc.

Third parties 9

Locations

2 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications