LBA43 - Intradermal IMO-2125 versus placebo as adjuvant treatment in patients with stage II pT3-4/cN0 melanoma: Interim efficacy and safety results of the randomized phase II INTRIM study

Background

Adjuvant immunotherapy is currently moving into earlier stages of melanoma. CPG7909, a Toll-like receptor-9 (TLR9) agonist, injected at the primary tumour excision site in patients with clinical stage I/II melanoma, was found to boost loco-regional and systemic anti-melanoma immunity. In an exploratory analysis this was accompanied by a significant decrease in tumour-positive sentinel lymph node (SLN) rates and improved recurrence-free survival (RFS). To confirm these results we performed a randomized, placebo-controlled and double-blind phase II study of TLR9 agonist IMO-2125 in stage II pT3-4/cN0 melanoma. We here report the interim efficacy and safety results.

Methods

Patients with pT3-4/cN0 melanoma, scheduled to undergo wide local excision and sentinel node biopsy (SNB), were randomized 1:1 to a single intradermal injection of 8mg of IMO-2125 vs. placebo at the primary tumour excision site, 7-10 days prior to surgery. The primary endpoint was SLN tumour status; secondary endpoints were SLN and peripheral blood immune status, RFS and overall survival (OS) after 5 and 10 years.

Results

From January 2020 to February 2022, 108 patients received IMO-2125 (n=54) or placebo (n=54). At interim analysis, the primary endpoint had been reached, i.e. IMO-2125 injected patients had a significantly reduced tumour positive SLN rate compared to placebo-treated patients (13% vs. 45%, P<0.0001), exceeding the pre-specified P-value of significance of 0.008. Notably, more patients in the placebo group had ulcerated melanoma, but stratified analysis for ulceration showed a similar trend. IMO-2125 treatment was mainly associated with grade 1 and 2 injection site reactions (54%), flu-like symptoms (46%), chills (41%) and fever (33%), accompanied by grade 3 confusion in one elderly patient.

Conclusions

Single-dose IMO-2125 has a reasonable safety profile and significantly reduces tumour positive SLN rates in pT3-T4 melanoma patients. Provided that SLN status accurately reflects future RFS, IMO-2125 has the potential to improve outcomes of early-stage melanoma patients.

Clinical trial identification

NCT04126876.

Editorial acknowledgement

Legal entity responsible for the study

VUmc Research BV.

Funding

Idera Pharmaceuticals.

Disclosure

B.D. Koster: Financial Interests, Personal, Full or part-time Employment: Janssen Biologics BV ; Non-Financial Interests, Personal, Member: ASH; Non-Financial Interests, Institutional, Member: EHA. M.W. Bekkenk: Financial Interests, Personal, Advisory Board: Janssen Pharmaceuticals, Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Almirall; Non-Financial Interests, Personal, Leadership Role: Netherlands Society for Experimental Dermatology (NVED), Netherlands Society for Drmatology and Venereology (NVDV), Chanfleury van IJsselstein Foundatoin; Non-Financial Interests, Personal, Member of the Board of Directors: Pigment Disorders Society of The Netherlands; Non-Financial Interests, Personal, Advisory Role: Vitiligo and Melanoma Society The Netherlands. M. Labots: Financial Interests, Institutional, Advisory Board: MSD, BMS; Financial Interests, Institutional, Training: BMS; Financial Interests, Institutional, Advisory Role: Caladrius Technologies; Non-Financial Interests, Personal, Member: ESMO, ASCO. S.K. Chunduru: Financial Interests, Personal, Full or part-time Employment: Idera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Idera Pharmaceuticals; Non-Financial Interests, Personal, Member: ESMO, American Chemical Society. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers-Squibb, Novartis, MSD - Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC, Provectus; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. F. Van Den Eertwegh: Financial Interests, Institutional, Research Grant, Grant for national trial: Roche; Financial Interests, Institutional, Research Grant, Grant for research project: BMS; Financial Interests, Institutional, Research Grant, Research grant for trial: Sonafi, Idera; Financial Interests, Institutional, Research Grant, Grant for trial: Teva; Non-Financial Interests, Advisory Role: BMS, Novartis, Pierre Fabre, MSD, Pfizer, Amgen, Ipsen, Merck. T.D. de Gruijl: Financial Interests, Institutional, Advisory Board: Lava Therapeutics, DCPrime, Macrophage Pharma; Financial Interests, Personal, Advisory Board: Partner Therapeutics; Financial Interests, Personal, Stocks/Shares: LAVA Therapeutics; Financial Interests, Personal, Invited Speaker, Patent: Immunoglobulins binding human Vγ9Vδ2 T cell receptors; P31885NL00: Lava Therapeutics; Financial Interests, Personal, Invited Speaker, Single domain antibodies targeting CD1d; P32016NL00; EP16715360.0-1412.: Lava Therapeutics; Financial Interests, Personal, Invited Speaker, Patent: Novel bispecific antibodies for use in the treatment of haematological malignancies. WO/2020/060406, PCT/NL2019/050625.: Lava Therapeutics; Financial Interests, Personal, Invited Speaker, Patent: Novel CD40 binding antibodies; WO/2020/159368; PCT/NL2020/050051: LAVA Therapeutics; Financial Interests, Personal, Invited Speaker, Patent: Recombinant replication competent viruses comprising a coding region for glycogen synthase kinase- (GSK3) and methods of killing aberrant cells. WO/2020/046130, PCT/NL2019/050562: ORCA Therapeutics; Financial Interests, Institutional, Invited Speaker, Research funding from Idera Pharmaceuticals for an investigator-initiated clinical trial (INTRIM) on the intra-dermal administration of IMO-2125 CpG in early-stage melanoma;: Idera Pharmaceuticals; Financial Interests, Institutional, Research Grant, Contract research with Macrophage Pharma Inc.”Pre-clinical testing of the immune modulating effects of MPL-5821 in the tumor microenvironment”: Macrophage Pharma; Non-Financial Interests, Leadership Role, Member of the Board of Directors: SITC, Society for the Immunotherapy of Cancer (SITC); Non-Financial Interests, Advisory Role, Member of the grant review committee: MRA; Non-Financial Interests, Advisory Role, Member of their scientific grant reviewing committee: KWF; Non-Financial Interests, Institutional, Product Samples, Provision of Durvalumab for a clinical trial: AstraZeneca; Non-Financial Interests, Institutional, Product Samples, Provision of nivolumab for clinical trials: BMS; Non-Financial Interests, Institutional, Product Samples, Provision of Pembrolizumab for clinical trials: Merck; Non-Financial Interests, Member: AACR. All other authors have declared no conflicts of interest.