NCT02977052: OpACIN-neo

Multicenter Phase 2 Study to Identify of the Optimal Neo-Adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo)

Status unknown Phase 2 Last updated 14 November 2023

What this trial tests

Phase 2 trial testing Ipilimumab in Malignant Melanoma Stage III in 186 participants. Status unknown.

Timeline

24 November 2016

Primary endpoint
3 January 2020

1 June 2025

Quick facts

Lead sponsor	The Netherlands Cancer Institute
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	186
Start date	24 November 2016
Primary completion	3 January 2020
Estimated completion	1 June 2025
Sites	4 locations across Australia, Austria, Netherlands, Sweden

Drugs / interventions tested

• Ipilimumab — full drug profile →
• Nivolumab (nivolumab) — full drug profile →
• Surgery
• Blood for PBMCs
• Biopsies — full drug profile →

Conditions studied

• Malignant Melanoma Stage III — all drugs for Malignant Melanoma Stage III →

Sponsor

The Netherlands Cancer Institute

Who can join

18 and older, any sex, with Malignant Melanoma Stage III. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Safety as measured by the frequency of grade 3/4 immune-related adverse events, using CTCAE 4.03
  Time frame: During the first 12 weeks.
• Response rate according to RECIST 1.1
  Time frame: At 6 weeks
• Pathological response according to central pathological revision, according to pathological response criteria
  Time frame: At 6 weeks
• Pathologic response rate according to central revision of the marked index lymph node
  Time frame: At 6 weeks, prior surgery
• RFS at 24 months in patients achieving pCR or pnCR in their marked index lymph node and did not undergo CLND. RFS will be calculated from date of resection of the marked lymph node.
  Time frame: 24 months
• RFS at 24 months in patients with pNR and being subsequently treated with adjuvant nivolumab+optional radiotherapy (or dabrafenib/trametinib if BRAFV600E pos. and treatment is approved). RFS will be calculated from day of resection of marked lymph node.
  Time frame: 24 months

Sponsor's own description

This is an open-label three-arm phase 2 trial (including a Simon stage 2 design) consisting of 90 stage III melanoma patients randomized 1:1:1 to receive either 2 courses 3 mg/kg ipilimumab + 1 mg/kg nivolumab every 3 weeks (Arm A), 2 courses 1 mg/kg ipilimumab + 3 mg/kg nivolumab every 3 weeks (Arm B), or 2 courses ipilimumab 3 mg/kg, directly followed by 2 courses nivolumab 3 mg/kg every 2 weeks (Arm C). All three treatment arms are applied prior to surgery at week 6, 30 patients per arm. Patients will be stratified according to treatment center. An interim analysis will be performed after 13 patients have been included in each arm, thus in total 39 patients have been included.

PRADO extension cohort The trial will enroll in total about 100-110 melanoma patients with macroscopic stage III disease (RECIST measurable disease); inclusion will stop when 50 patients have achieved a pCR or pnCR. All patients will be treated (after marker placement into the largest lymph node metastasis) with the winner combination identified in the first part of the OpACIN-neo study which is 2 courses ipilimumab 1mg/kg + nivolumab 3mg/kg, q3wks. After 6 weeks of treatment, the patients will undergo only surgical resection of the marked index lymph node. Thereafter subsequent surgery and adjuvant therapy will be performed according to the achieved pathologic response.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.
   Chan TA, Yarchoan M, Jaffee E, Swanton C, et al · · 2019 · cited 2009× · PMID 30395155 · DOI 10.1093/annonc/mdy495
2. Neoadjuvant checkpoint blockade for cancer immunotherapy.
   Topalian SL, Taube JM, Pardoll DM. · · 2020 · cited 741× · PMID 32001626 · DOI 10.1126/science.aax0182
3. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.
   Amaria RN, Reddy SM, Tawbi HA, Davies MA, et al · · 2018 · cited 637× · PMID 30297909 · DOI 10.1038/s41591-018-0197-1
4. Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.
   Patel SP, Othus M, Chen Y, Wright GP, et al · · 2023 · cited 596× · PMID 36856617 · DOI 10.1056/nejmoa2211437
5. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial.
   Rozeman EA, Menzies AM, van Akkooi ACJ, Adhikari C, et al · · 2019 · cited 396× · PMID 31160251 · DOI 10.1016/s1470-2045(19)30151-2
6. Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC).
   Chae YK, Arya A, Iams W, Cruz MR, et al · · 2018 · cited 336× · PMID 29769148 · DOI 10.1186/s40425-018-0349-3
7. Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma.
   Rozeman EA, Hoefsmit EP, Reijers ILM, Saw RPM, et al · · 2021 · cited 259× · PMID 33558721 · DOI 10.1038/s41591-020-01211-7
8. Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial.
   Reijers ILM, Menzies AM, van Akkooi ACJ, Versluis JM, et al · · 2022 · cited 248× · PMID 35661157 · DOI 10.1038/s41591-022-01851-x