Mini Oral session
Date
18.09.2020
Chairs
  • Helen J. Gogas (Athens, Greece)
  • Ana Maria Arance Fernandez (Barcelona, Spain)
Mini Oral - Melanoma and other skin tumours Mini Oral session

Open & welcome

Speakers
  • Ana Maria Arance Fernandez (Barcelona, Spain)
Mini Oral - Melanoma and other skin tumours Mini Oral session

LBA47 - Primary analysis of phase II results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs)

Presentation Number
LBA47
Speakers
  • Alexander J. Stratigos (Athens, Greece)

Abstract

Background

There is no approved therapeutic option post-HHI for pts with laBCC. Cemiplimab, an antibody to PD-1, is an established therapy approved for treatment of advanced cutaneous squamous cell carcinoma (CSCC) in pts who are not candidates for curative surgery or curative radiation. Both BCC and CSCC are keratinocytic tumours with high mutational burden due to ultraviolet mutagenesis and are potentially amenable to immunotherapy. We present the primary analysis of the laBCC cohort from the pivotal phase II study of cemiplimab in the second-line (or greater) setting.

Methods

Pts with laBCC received cemiplimab 350 mg Q3W IV (for up to 93 weeks or until progression). The primary endpoint was objective response rate (ORR) by Independent Central Review (ICR). Secondary objectives included assessment of safety and tolerability, estimation of duration of response (DOR), progression-free survival (PFS) and overall survival (OS). ORR included two responses confirmed after the data cut-off date of 17 February 2020.

Results

84 pts were enrolled; 66.7% male; median age was 70 years (range: 42−89). Median follow-up was 15 months (range: 0.5−25). ORR per ICR was 31% (95% CI: 21−42), including five complete responses and 21 partial responses. Median DOR has not been reached; an estimated 85% of responses were ongoing at 12 months, per the Kaplan–Meier method. Median PFS and OS had not been reached. Estimated PFS for all patients was 19 months. The most common adverse events (AEs) were fatigue (30%), diarrhoea (24%) and pruritus (21%); 17% of patients discontinued treatment due to AEs. Median baseline tumour mutational burden (TMB) was 58.2 and 23.5 mutations/Mb among responding (n=18) and non-responding (n=38) pts, respectively, but responses occurred at all TMB levels. Exploratory biomarker analysis identified downregulation of major histocompatibility complex-I expression as a potential immune evasion mechanism in non-responding BCCs with high TMB.

Conclusions

Cemiplimab is the first agent to establish clinical benefit for pts with laBCC who progress on or are intolerant to HHI therapy, regardless of biomarker status.

Clinical trial identification

NCT03132636.

Editorial acknowledgement

Medical writing support was provided by Cindi Hoover, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc. and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

A.J. Stratigos: Advisory/Consultancy: Janssen Cilag; Advisory/Consultancy: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy: Sanofi; Research grant/Funding (self): AbbVie; Research grant/Funding (self): BMS; Research grant/Funding (self): Genesis Pharma; Research grant/Funding (self): Novartis. A. Sekulic: Advisory/Consultancy: Regeneron Pharmaceuticals, Inc ; Advisory/Consultancy: Roche. K. Peris: Advisory/Consultancy, outside the submitted work: AbbVie; Advisory/Consultancy, outside the submitted work: Leo Pharma; Advisory/Consultancy, outside the submitted work: Janssen; Advisory/Consultancy, outside the submitted work: Almirall; Advisory/Consultancy, outside the submitted work: Lilly; Advisory/Consultancy, outside the submitted work: Galderma; Advisory/Consultancy, outside the submitted work: Novartis; Advisory/Consultancy, outside the submitted work: Pierre Fabre; Advisory/Consultancy, outside the submitted work: Sanofi. O. Bechter: Advisory/Consultancy: Novartis; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Ultimovacs. K.D. Lewis: Research grant/Funding (self): University of Colorado; Research grant/Funding (self), Grants and personal fees: Regeneron Pharmaceuticals, Inc. N. Basset-Seguin: Full/Part-time employment: Sun Pharmaceutical Industries, Inc.; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Galderma; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Leo; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Licensing/Royalties, Patents, royalties, or other intellectual property: Genentech/F. Hoffmann-La Roche, Ltd. A.L.S. Chang: Advisory/Consultancy, Research grant/Funding (self): Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, Research grant/Funding (self): Merck; Research grant/Funding (self): Novartis; Research grant/Funding (self): Galderma. S. Dalle: Spouse/Financial dependant, Spouse is an employee of Sanofi: Sanofi. L. Licitra: Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: MSD; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Received funding (for Institution) for clinical studies and research: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Debiopharm; Advisory/Consultancy: Sobi; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Medpace; Research grant/Funding (institution): IRX Therapeutics; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Incyte Biosciences; Advisory/Consultancy: Doxa Pharma; Advisory/Consultancy: Amgen; Advisory/Consultancy: Nanobiotics SA; Advisory/Consultancy: GlaxoSmithKline; Speaker Bureau/Expert testimony: AccMed; Speaker Bureau/Expert testimony: Medical Science Fundation G. Lorenzini; Speaker Bureau/Expert testimony: Associazione Sinapsi; Speaker Bureau/Expert testimony: Think 2 IT; Speaker Bureau/Expert testimony: Aiom Servizi; Speaker Bureau/Expert testimony: Prime Oncology; Speaker Bureau/Expert testimony: WMA Congress Education; Speaker Bureau/Expert testimony: Fasi, DueCi promotion Srl, MI&T, Net Congress & Education, PRMA Consulting, Kura Oncology, Health & Life srl, Immuno-Oncology Hub. C. Robert: Advisory/Consultancy: BMS; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Biothera; Advisory/Consultancy: Ultimovacs. C. Ulrich: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sun Pharma. A. Hauschild: Research grant/Funding (institution), and personal fees: Amgen; Research grant/Funding (institution), And personal fees: BMS; Research grant/Funding (institution), and personal fees: MerckSerono; Research grant/Funding (institution), and personal fees: MSD/Merck; Research grant/Funding (institution), and personal fees: Philogen; Research grant/Funding (institution), and personal fees: Pierre Fabre; Research grant/Funding (institution), and personal fees: Provectus; Research grant/Funding (institution), and personal fees: Regeneron Pharmaceuticals, Inc.; Research grant/Funding (institution), and personal fees: Roche; Research grant/Funding (institution), and personal fees: Sanofi-Genzyme; Research grant/Funding (institution), and personal fees: Novartis; Advisory/Consultancy: OncoSec; Advisory/Consultancy: Sun Pharma. M.R. Migden: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, Travel/Accommodation/Expenses: Sun Pharmaceuticals; Advisory/Consultancy: Rakuten Medical; Research grant/Funding (self): Pelle Pharm. R. Dummer: Advisory/Consultancy, outside the submitted work: Novartis; Advisory/Consultancy, outside the submitted work: Merck Sharp & Dhome; Advisory/Consultancy, outside the submitted work: Bristol-Myers Squibb; Advisory/Consultancy, outside the submitted work: Roche; Advisory/Consultancy, outside the submitted work: Amgen; Advisory/Consultancy, outside the submitted work: Takeda; Advisory/Consultancy, outside the submitted work: Pierre Fabre; Advisory/Consultancy, outside the submitted work: Sun Pharma; Advisory/Consultancy, outside the submitted work: Sanofi; Advisory/Consultancy, outside the submitted work: Catalym; Advisory/Consultancy, outside the submitted work: Second Genome; Advisory/Consultancy, outside the submitted work: Regeneron Pharmaceuticals, Inc.; Advisory/Consultancy, outside the submitted work: Alligator. S. Li: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. T. Bowler: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. M.G. Fury: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Patent holder: of Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

1077MO - PD1 blockade with pembrolizumab in classic and endemic Kaposi sarcoma: A multicenter phase II study

Presentation Number
1077MO
Speakers
  • Julie Delyon (Paris, France)

Abstract

Background

While the treatment of iatrogenic and HIV-related KS is well defined, mostly based on restoring the immune function, the treatment of classic/endemic KS is less codified. Chemotherapy or interferon are used for patients (pts) with extensive cutaneous and/or visceral KS but the tolerance may be poor in elderly pts, and long-term remissions are rare. Major efficacy of PD1 blockade has been demonstrated in Merkel cell carcinoma, another virus-induced tumor, in part driven by the immunogenicity of virus-associated antigens. Because of the involvement of HHV8 in KS and their good tolerance in older pts, the use of anti-PD1 appeared as a promising tool for classic/endemic KS.

Methods

We conducted a multicenter single arm phase II trial in pts with classic/endemic KS with cutaneous extension requiring systemic treatment. Pts were treated with pembrolizumab (pembro) 200mg every 3 weeks for 6 months. Tumor assessment was performed by physical examination at each cycle (count, size, nodularity and color of target cutaneous lesions). The primary endpoint was the best overall response rate (BORR, ACTG criteria). A tumor response probability >30% using the Simon’s 2 stage optimal design was required to conclude that the drug was active.

Results

17 pts (47% with classic and 53% with endemic KS) were included. 6 pts (35%) had lymph node extension. 12 pts (71%) were previously treated with chemotherapy. Median follow up was 25 weeks. Two pts had CR, 10 PR and 4 SD as best response (1 still on treatment; threshold of drug activity achieved). One pt discontinued treatment for toxicity. Treatment-related adverse events occurred in 11 pts (65%), including 1 grade 3 (6% - acute reversible cardiac decompensation). On baseline tumor samples, the lack of PDL1 expression on tumor and immune cells was associated with poor efficacy of pembro. The germline HLA-1 evolutionary divergence (HED) was determined for 16 pts. The 4 pts with SD as best response had significantly lower HED for HLA-B than pts with PR or CR.

Conclusions

In the first prospective trial assessing the role of PD1 blockade in classic/endemic KS, pembro showed efficacy with 12 out of 16 of pts having CR or PR (BORR above 30%) and had an acceptable safety profile. If confirmed, this treatment could rapidly become standard of care.

Clinical trial identification

NCT03469804.

Legal entity responsible for the study

AP-HP.

Funding

MSD.

Disclosure

J. Delyon: Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: Roche. S. Dalle: Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Research grant/Funding (institution): Roche. V. Heidelberger: Travel/Accommodation/Expenses: UCB Pharma; Travel/Accommodation/Expenses: MSD. G. Carcelain: Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Gilead; Speaker Bureau/Expert testimony: ViiV Healthcare. S. Mourah: Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Biocartis; Advisory/Consultancy: Roche. M. Battistella: Advisory/Consultancy: BMS; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Takeda; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Kyowa Kirin. C. Lebbé: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Research grant/Funding (institution): GSK; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (institution): Amgen. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

1078MO - MIND-DC: A randomized phase III trial to assess the efficacy of adjuvant dendritic cell vaccination in comparison to placebo in stage IIIB and IIIC melanoma patients

Presentation Number
1078MO
Speakers
  • Kalijn Bol (Nijmegen, Netherlands)

Abstract

Background

Dendritic cells (DCs) are highly specialized antigen-presenting cells which are essential for the activation of immune responses. Autologous DCs, directly isolated from peripheral blood, loaded with tumor antigens and matured in vitro, can induce tumor-specific immune responses and clinical responses in cancer patients.

Methods

In this phase III clinical trial, patients with resected stage IIIB or IIIC cutaneous melanoma (AJCC 7th edition) were randomized in a 2:1 ratio to adjuvant treatment with DC vaccination or placebo. The active treatment arm consisted of intranodal injections with autologous CD1c+ myeloid DCs and plasmacytoid DCs loaded with tumor antigens (gp100, tyrosinase, MAGE-C2, MAGE-A3 and NY-ESO-1). When adjuvant treatment with anti-PD1 antibodies became available in the Netherlands in November 2018, accrual was stopped prematurely after inclusion of 151 patients. The primary endpoint is the 2-year recurrence-free survival (RFS) rate. Secondary endpoints include overall survival, immunological response and safety.

Results

In January 2020, we performed a preplanned interim analysis. At that time, 102 patients reached mature data for primary endpoint analysis (recurrence of disease within 2 years of randomisation or at least 2-year follow-up). Thirty-eight percent of patients were female and the median age at start was 55.7 years (range 27-78). At inclusion, 51% of patients had stage IIIB disease and 49% stage IIIC disease. Two-year RFS rate was 21.4% in the treatment arm and 25% in the control arm (HR 1.05; 95% CI: 0.47-3.23), providing no statistically significant evidence of a treatment effect (p=0.67).

Conclusions

Our phase III clinical trial with adjuvant DC vaccination in stage IIIB and IIIC melanoma patients showed no benefit over placebo in terms of 2-year RFS. Correlative analysis of skin-test infiltrating lymphocytes for markers of immunological and clinical response are ongoing.

Clinical trial identification

NCT02993315.

Legal entity responsible for the study

Radboud University Medical Centre Nijmegen.

Funding

ZonMw, Ministry of Health, Welfare and Sport (VWS), Miltenyi Biotec (in-kind).

Disclosure

A.A.M. Van der Veldt: Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sanofi. J.W.B. de Groot: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Servier. W.R. Gerritsen: Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: IMS Health; Advisory/Consultancy: IQVIA; Advisory/Consultancy, Research grant/Funding (institution): Janssen-Cilag; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Bayer. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

Invited Discussant LBA47, 1077MO and 1078MO

Speakers
  • Salvador Martin Algarra (Pamplona, Spain)
Mini Oral - Melanoma and other skin tumours Mini Oral session

1079MO - Progression of BRAF mutant CNS metastases are associated with a transcriptional network bearing similarities with the innate PD-1 resistant signature (IPRES)

Presentation Number
1079MO
Speakers
  • Peter K. Lau (Nedlands, WA, Australia)

Abstract

Background

Melanoma CNS metastases are a common problem that causes high morbidity and mortality. Although first line dabrafenib-trametinib and ipilimumab-nivolumab (I-N) have similar intracranial response rates (50-55%), durable responses are only seen with combination immunotherapy and CNS resistance to BRAF-MEK inhibitors (BRAF-MEKi) usually occurs within 6 months. We sought to investigate the utility of I-N after BRAF-MEKi CNS progression and identify resistance mechanisms.

Methods

All patients receiving second/third line I-N for CNS metastases from 1/3/15 to 1/8/18 with prior progression on BRAF-MEKi and MRI brain staging were included. Modified intracranial RECIST was used to assess response. Formalin fixed paraffin embedded samples of BRAF V600 mutant CNS metastases naïve to treatment (n=18) or excised after progression on BRAF-MEKi (n=14) underwent whole transcriptome sequencing. Comparative analyses of CNS samples naïve to systemic treatment versus BRAF-MEKi progression was performed.

Results

Thirty patients received second/third line I-N with median CNS diameter of 21 mm. Modest efficacy of I-N after BRAF-MEKi progression was observed with an intracranial response rate of 4.8% (1/21) and median PFS of 5.5 weeks. Given the poor activity of I-N after BRAF-MEKi CNS progression we investigated the mechanisms that also conferred resistance to immunotherapy. We identified 179 differentially expressed genes (DEG) between naïve and BRAF-MEKi progression CNS metastases (p < 0.05, false discovery rate [FDR] < 0.1). Gene set enrichment analysis with KEGG, GO or Hallmark libraries did not identify distinct pathways. Enrichment of DEG from the Innate anti-PD1 Resistance Signature (IPRES) was identified (p < 0.01, FDR = 0.03). Macrophage associated chemokines and myeloid activation genes were upregulated in CNS progression samples. Histological assessment showed increased macrophage grading in BRAF-MEKi progression samples (mean 1.45 vs 0.45, p=0.009).

Conclusions

I-N after CNS BRAF-MEKi progression has modest intracranial activity. CNS metastases resistant to BRAF-MEKi showed expression of the IPRES gene signature and upregulation of myeloid cell activation markers.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P.K.H. Lau: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Pfizer. D. Kee: Honoraria (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Novartis. P. Neeson: Research grant/Funding (self): Bristol-Myers Squibb. S. Sandhu: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Amgen; Honoraria (self): Merk Sharp & Dohme; Honoraria (self): Janssen. G. McArthur: Research grant/Funding (institution), Principal Investigator of clinical trials with the following commercial entities (all revenues payed to my institution as reimbursement for trial- costs): Bristol-Myers Squibb; Research grant/Funding (institution), Principal Investigator of clinical trials with the following commercial entities (all revenues payed to my institution as reimbursement for trial- costs): Array BioPharm; Research grant/Funding (institution), Principal Investigator of clinical trials with the following commercial entities (all revenues payed to my institution as reimbursement for trial- costs): Amgen; Research grant/Funding (institution), Principal Investigator of clinical trials with the following commercial entities (all revenues payed to my institution as reimbursement for trial- costs): Pfizer. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

1080MO - The value of local therapy in treatment of solitary melanoma progression upon immune checkpoint inhibition

Presentation Number
1080MO
Speakers
  • Judith M. Versluis (Amsterdam, Netherlands)

Abstract

Background

Patients (pts) with stage IV melanoma can achieve long-term disease control through treatment with immune checkpoint inhibition (ICI). Disease progression in a single tumor lesion (solitary progression, SP) after initial response to ICI is often treated with local therapy. This study aimed to evaluate the benefits of local therapy for the treatment of SP during (on) or after cessation of (off) ICI.

Methods

Pts with stage IV melanoma with at least stable disease (SD) as best overall response (BOR) upon ICI and SP as first progressive event were retrospectively included from 17 centers in 9 countries.

Results

We included 294 pts with SP on anti-PD-1 (67%), anti-CTLA-4 (13%), anti-PD-1 + anti-CTLA-4 (15%) and other ICI combinations (5%). BOR prior to SP was SD (15%), partial response (55%) and complete response (30%). Local therapy was mainly surgery (56%), radiotherapy (35%) or both (5%). Median follow-up from start ICI was 43 months (m), median time to SP 13m and median time to second progression after treatment of SP (TTSP) 33m. Median overall survival (OS) was not reached, estimated 3-year OS was 79%. SP occurred in 143 pts on ICI (median 11m) and in 151 pts off ICI (median 17m from start ICI, 9m from stop ICI). SP was treated with local + systemic therapy (42%), local therapy (36%) or systemic therapy only (18%). Second progression was mostly progression at multiple sites (64% and 65% for SP on and off ICI). In pts with SP on ICI, median TTSP was 29m. Local therapy + ICI continuation (N=94) resulted in similar 3-year TTSP as local therapy (N=15) or ICI continuation only (N=14, P=0.971). OS at 3 years was superior for local therapy + ICI continuation (P=0.020). In pts with SP off ICI, median TTSP was 35m. ICI restart + local therapy (N=22, 85%) resulted in superior TTSP compared to local therapy (N=90, 41%) or ICI restart (N=18, 56%, P=0.002), without OS differences so far.

Conclusions

In pts with SP off ICI, the combination of local therapy + ICI restart was most successful in delaying further progression, but did not improve OS so far compared to single modality treatment. Local therapy + ICI continuation in pts with SP on ICI did not improve TTSP, but did improve OS. This indicates that local therapy can benefit pts.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

K.P.M. Suijkerbuijk: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. L. Zimmer: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Sunpharma. E. Kapiteijn: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Roche. C. Allayous: Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Roche. D.B. Johnson: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Genentech. A. Hepner: Honoraria (institution): Novartis; Advisory/Consultancy: L.E.K. Consulting; Travel/Accommodation/Expenses: Roche. J. Mangana: Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (institution), Advisory/Consultancy: Merck-Pfizer; Honoraria (institution): Novartis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: L'Oreal; Travel/Accommodation/Expenses: Ultrasun. Y. Jansen: Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer. V. Atkinson: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: OncoSec. E.G.E. de Vries: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: NSABP; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Chugai Pharma; Research grant/Funding (institution): CytomX Therapeutics; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Nordic Nanavector; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Synthon; Non-remunerated activity/ies, Chair ESMO Cancer Medicines Working Group: ESMO; Non-remunerated activity/ies, Chair RECIST committee: RECIST; Non-remunerated activity/ies, Member ESMO-MCBS working group: ESMO-MCBS. C.U. Blank: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): NanoString; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: GSK; Honoraria (institution), Advisory/Consultancy: AZ; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: GenMab; Honoraria (institution), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Third Rock Ventures; Shareholder/Stockholder/Stock options: Uniti Cars; Shareholder/Stockholder/Stock options: Immagene BV. M. Jalving: Honoraria (institution): Merck; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Novartis; Honoraria (institution): Pierre Fabre; Honoraria (institution): Tesaro; Honoraria (institution): AstraZeneca. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

1081MO - Efficacy of ipilimumab plus nivolumab or ipilimumab plus fotemustine vs fotemustine in patients with melanoma metastatic to the brain: Primary analysis of the phase III NIBIT-M2 trial

Presentation Number
1081MO
Speakers
  • Anna M. Di Giacomo (Siena, Italy)

Abstract

Background

Brain metastases (BM) represent a high-unmet medical need, in which the therapeutic potential of immune-checkpoint(s) (ICI) is being actively investigated. Temozolomide and fotemustine (FTM) have been the therapeutic mainstay of melanoma (MM) patients (pts) with BM for over two decades. The Italian Network for Tumor Biotherapy (NIBIT)-M1 trial firstly demostrated signs of activity of ipilimumab (Ipi) combined with FTM in a subset of 20 MM pts with active BM (Di Giacomo, Lancet Oncol, 2012), with a 3-year survival rate of 28% (Di Giacomo, Annals Oncol, 2015). Two subsequent phase II studies reported the efficacy of Ipi combined with nivolumab (Nivo) in MM pts with asymptomatic BM (Twabi, NEJM 2018; Long, Lancet Oncol 2018). We here report the results of the primary analysis of the NIBIT-M2 study, the first phase III trial that explored the efficacy of Ipi plus Nivo in MM pts with BM.

Methods

The NIBIT-M2 is a phase III, multicenter, open-label study in MM pts with active, untreated, and asymptomatic BM. BRAF wilde type or mutant pts were randomized to receive FTM (ARM A), the combination of Ipi and FTM (ARM B), or the combination of Ipi and Nivo (ARM C). Primary objective was overall survival (OS); among secondary were intracranial (i) objective response rate (iORR), i disease control rate (iDCR), and progression free survival (PFS).

Results

From January 2013 to September 2018, 96 MM pts were enrolled, 80 randomized, and 76 were treated: 23 in ARM A, 26 in ARM B, and 27 in ARM C. With a median follow-up of 39 months (mo), median OS was 8.5 mo (CI, 95%: 4.8-12.2) for ARM A, 8.2 mo (CI, 95%: 2.0-14.3) for ARM B, and 29.2 mo (CI, 95%: not yet evaluable) for ARM C. The iORR was 0%, 19.2% and 44.4% in ARM A, B, and C, respectively. The iDCR was 26.1%, 34.6% and 55.6% in ARM A, B, and C, respectively. Median PFS was 3.0 mo (CI, 95%: 2.3-3.6), 3.3 mo (CI, 95%: 1.2-5.4), and 8.4 mo (CI,95%: 4.2-12.7), in ARM A, B, and C, respectively.

Conclusions

Unlike Ipi plus FTM, Ipi plus Nivo significantly (p=0.009) improves the long-term survival of MM pts with BM, compared to FTM. Ipi plus Nivo should represent the treatment of choice in first line MM pts with BM.

Clinical trial identification

NCT02460068.

Legal entity responsible for the study

NIBIT Foundation.

Funding

Bristol-Myers Squibb.

Disclosure

A.M. Di Giacomo: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy: GSK; Advisory/Consultancy: Sanofi. V. Chiarion Sileni: Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses, Educational Activities: Pierre Fabre; Honoraria (self), Educational Activities: Merck Serono; Honoraria (self), Educational Activities: Novartis. M. Del Vecchio: Advisory/Consultancy: Novartis; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sanofi. P.F. Ferrucci: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre. M. Guida: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD. P. Quaglino: Honoraria (self), Advisory/Consultancy, Educational Activities: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Educational Activities: MSD; Honoraria (self), Advisory/Consultancy, Educational Activities: Novartis; Honoraria (self), Advisory/Consultancy, Educational Activities: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Educational Activities: Igea; Honoraria (self), Advisory/Consultancy, Educational Activities: Roche. M. Guidoboni: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Research grant/Funding (self): MSD. P. Marchetti: Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Boehringer; Research grant/Funding (self): Celgene. L. Calabrò: Advisory/Consultancy: MSD; Advisory/Consultancy: Bristol-Myers Squibb. R. Danielli: Advisory/Consultancy: Merck Serono. M. Mandala: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Research grant/Funding (self): Roche. M. Maio: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Alfasigma. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

Invited Discussant 1079MO, 1080MO and 1081MO

Speakers
  • Helen J. Gogas (Athens, Greece)
Mini Oral - Melanoma and other skin tumours Mini Oral session

LBA48 - Clinical efficacy and immunity of combination therapy with nivolumab and IDO/PD-L1 peptide vaccine in patients with metastatic melanoma: A phase I/II trial

Presentation Number
LBA48
Speakers
  • Inge-Marie Svane (Herlev, Denmark)

Abstract

Background

The IDO/PD-L1 (IO102/IO103)1 peptide vaccine is a first-in-class immunomodulatory vaccine containing single IDO- and PD-L1-derived long peptide sequences designed to engage and activate IDO and PD-L1 specific T-cells mediating immune switch. This non-randomized phase I/II study evaluates the IDO/PD-L1 peptide vaccine in combination with nivolumab in patients with progressive metastatic melanoma. Here we report safety, efficacy, and immune response data.

Methods

Thirty treatment naive stage IV melanoma patients received a maximum of 15 IDO/PD-L1 vaccine doses SC (6x q2w followed by 9x q4w). Nivolumab (3 mg/kg) was administered every second week (q2w) until intolerable toxicity or tumor progression. The objectives were to assess safety, immune response in blood and biopsies as well as efficacy.

Results

As of the data cut-off, August 2020, all 30 patients were enrolled with a median follow up of 15 months. 1 patient is pending first evaluation, 29 were evaluated and by investigator review per RECIST v1.1 an overall response rate (ORR) of 79% was reached; ORR was 94% and 62% in PD-L1 positive and negative patients, respectively. At data cut-off, 45% have reached complete response and 34% partial response, which was significantly higher than a matched control group extracted from the DAMMED database receiving anti-PD-1 monotherapy treatment as standard of care. The median progression free survival (mPFS) was 25,6 months. Except for local reactions at vaccination site toxicity was comparable to patients receiving nivolumab monotherapy. Vaccine specific T-cells against either IDO and/or PD-L1 were detectable in PBMC from all treated patients and in a number of patients at the tumor site where a biopsy was feasible. Preliminary results from tumor immune contexture analyses were indicative for response.

Conclusions

The combination of IDO/PD-L1 peptide vaccine and nivolumab is safe with encouraging early efficacy data; an ORR of 79% was reached and 45% achieved complete response. Vaccine specific T-cells were demonstrated in PBMCs and tumor site. ClinicalTrials.gov Identifier: NCT03047928 1 IO Biotech (www.iobiotech.com) has licensed the patent of the vaccine IO102/IO103 T-win®.

Clinical trial identification

NCT03047928.

Legal entity responsible for the study

Inge Marie Svane.

Funding

Has not received any funding.

Disclosure

I-M. Svane: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Officer/Board of Directors: IO Biotech; Honoraria (self): BMS; Honoraria (self), Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Honoraria (self): AbbVie; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self): Sanofi Genzyme; Honoraria (self): Ipsen; Advisory/Consultancy: InCyte; Honoraria (self): Merch; Honoraria (self): Roche; Advisory/Consultancy: Celgene. M.H. Andersen: Shareholder/Stockholder/Stock options, Officer/Board of Directors: IO Biotech. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

1082MO - 5-year characterization of complete responses in patients with advanced melanoma who received nivolumab plus ipilimumab (NIVO+IPI) or NIVO alone

Presentation Number
1082MO
Speakers
  • Caroline Robert (Villejuif, France)

Abstract

Background

5-year outcomes of patients (pts) with a CR to NIVO+IPI or NIVO alone and factors associated with continued CR or relapse are unknown. The current pooled analysis addresses these key questions, including a 12-mo CR landmark analysis used to decrease the time guarantee bias.

Methods

In this post hoc analysis, 5-yr data were pooled from the phase III CheckMate 066 and 067 studies and the phase II CheckMate 069 study of pts with treatment-naive, advanced melanoma. Analyzed pts received either the approved regimen of NIVO+IPI followed by NIVO monotherapy or NIVO monotherapy. Characteristics and outcomes of pts with a CR (by RECIST) were investigated, including 12-mo landmark survival analyses to determine the likelihood of being alive at 5-y among pts in CR by 12 mo (to mitigate the time guarantee bias).

Results

Minimum follow-up was 60 mo since randomization of the last pt in each study; pooled median mo of follow-up was 63 for NIVO+IPI (n=409) and 64 for NIVO (n=526). CRs were demonstrated in 96 (23%) NIVO+IPI pts and 102 (19%) NIVO pts; of CR pts alive at 5 yrs, 75/79 (95%) and 85/91 (93%) had not received subsequent systemic therapy. Baseline characteristics significantly associated with CR (Table) were M stage (NIVO+IPI), PD-L1 ≥ 5% (NIVO), normal lactate dehydrogenase (LDH; both) and fewer disease sites (both). Median duration of CR and median time to subsequent systemic therapy were not reached in either group. Median mo (Q1, Q3) to CR was 9.1 (2.8, 23.1) for NIVO+IPI and 11.8 (5.8, 26.5) for NIVO alone. In pts in CR at 12-mo, 5-y OS for NIVO+IPI and NIVO respectively was 85% and 86%; PFS was 84% and 82%.

Conclusions

NIVO+IPI- or NIVO-treated pts in CR at 12 mo have a high likelihood of being alive at 5 y even without subsequent systemic therapy. Several baseline pt characteristics were associated with CR duration. Factors associated with CR may differ for NIVO+IPI and NIVO alone. Biomarker analyses are ongoing.

NIVO+IPI NIVO
n/N CR % (95% CI) P-value n/N CR % (95% CI) P-value
LDH status >ULN ≤ULN 16/138 80/269 12 (7-18) 30 (24-36) <0.0001 19/191 81/317 10 (6-15) 26 (21-31) <0.0001
LDH status > 2xULN ≤ 2xULN 2/43 94/364 5 (1-16) 26 (21-31) 0.0020 2/58 98/450 3 (<1-12) 22 (18-26) 0.0010
M stage M0 M1A M1B M1C 9/19 20/62 30/98 37/229 47 (24-71) 32 (21-45) 31 (22-41) 16 (12-22) 0.0004 8/35 15/70 30/110 49/311 23 (10-40) 21 (12-33) 27 (19-37) 16 (12-20) 0.0587
No. lesion sites 1 2-3 >3 53/128 36/211 7/70 41 (33-50) 17 (12-23) 10 (4-20) <0.0001 40/130 50/303 12/91 31 (23-40) 16 (12-21) 13 (7-22) 0.0007
PD-L1 ≥5% <5% 20/92 64/266 22 (14-32) 24 (19-30) 0.6507 42/139 58/335 30 (23-39) 17 (13-22) 0.0017

ULN, upper limit of normal.

Clinical trial identification

NCT01721772; NCT01927419; NCT01844505.

Editorial acknowledgement

Writing and editorial assistance were provided by Melissa Kirk, PhD, and Michele Salernitano of Ashfield Healthcare Communications, funded by Bristol-Myers Squibb Company.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

C. Robert: Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Biothera; Advisory/Consultancy: Ultimovacs. G.V. Long: Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy: Amgen Inc.; Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Mass-Array; Advisory/Consultancy: Merck & Co., Inc.; Advisory/Consultancy: Merck Sharp & Dohme Corp.; Advisory/Consultancy: Novartis; Advisory/Consultancy: OncoSec Medical Incorporated; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: Roche; Advisory/Consultancy: Sandoz International GmbH. J. Larkin: Advisory/Consultancy, Research grant/Funding (self): Achilles Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb Company; Advisory/Consultancy: Eisai Co., Ltd.; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Ipsen Pharma; Advisory/Consultancy: Imugene Limited; Advisory/Consultancy: Incyte; Advisory/Consultancy: iOnctura; Advisory/Consultancy: Kymab; Advisory/Consultancy: Merck Sorono; Advisory/Consultancy, Research grant/Funding (self): Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (self): Nektar; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy, Research grant/Funding (self): Pfizer Inc.; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Secarma; Advisory/Consultancy: Vitaccess; Advisory/Consultancy: Covance Inc.; Advisory/Consultancy, Research grant/Funding (self): Immunocore, Ltd.; Advisory/Consultancy: AVEO Pharmaceuticals, Inc.; Advisory/Consultancy: Pharmacyclics LLC. J.D. Wolchok: Advisory/Consultancy, Shareholder/Stockholder/Stock options: BeiGene; Shareholder/Stockholder/Stock options: Linneaus Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Arsenal-Caprion; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Sephora; Advisory/Consultancy: Amgen Inc.; Advisory/Consultancy: Apricity Therapeutics, Inc.; Advisory/Consultancy: Ascentage Pharma; Advisory/Consultancy: Astellas Pharma US, Inc.; Advisory/Consultancy: Bayer AG; Advisory/Consultancy: Celgene; Advisory/Consultancy: Chugai Pharmaceutical Co., Ltd.; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Elucida Oncology, Inc.; Advisory/Consultancy: F-star Biotechnology Limited; Advisory/Consultancy: Kyowa Kirin Co., Ltd.; Advisory/Consultancy: Merck and Co., Inc.; Advisory/Consultancy: Neon Therapeutics; Advisory/Consultancy: Polynoma LLC; Advisory/Consultancy: PsiOxus Therapeutics; Advisory/Consultancy: Recepta Biopharma; Speaker Bureau/Expert testimony: Takara Bio Inc.; Advisory/Consultancy: Trieza Therapeutics; Advisory/Consultancy: Truvax Inc.; Advisory/Consultancy: Serametrix; Advisory/Consultancy: Surface; Advisory/Consultancy: Syndax Pharmaceuticals Inc.; Advisory/Consultancy: Syntalogic Pharmaceuticals, Inc. J.C. Hassel: Speaker Bureau/Expert testimony, Research grant/Funding (self), Payments for patient treatment in clinical trial: Bristol-Myers Squibb Company; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: Sun Pharma. D. Schadendorf: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen Inc.; Honoraria (self), Advisory/Consultancy: Immunocore, Ltd.; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Incyte; Honoraria (self), Advisory/Consultancy: 4SC; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre Group; Advisory/Consultancy: Sanofi/Regeneron; Travel/Accommodation/Expenses: Merck & Co., Inc.; Honoraria (self): Agenus Inc.; Honoraria (self): Array BioPharma; Honoraria (self): Pfizer; Honoraria (self): Philogen; Honoraria (self): Regeneron; Advisory/Consultancy: Nektar; Advisory/Consultancy: Sandoz. F.S. Hodi: Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck & Co., Inc.; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Licensing/Royalties: Novartis; Advisory/Consultancy: Takeda, Surface Pharmaceuticals, Compass Therapeutics, Verastem, Rheos, Amgen; Licensing/Royalties: Therapeutic Peptides Therapeutic Peptides Patent number: 9402905; Honoraria (self), Advisory/Consultancy: Genentech/Roche; Licensing/Royalties: Methods of Using Pembrolizumab and Trebananib Vaccine compositions and methods for restoring NKG2D pathway function against cancers Patent number: 10279021; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Apricity Therapeutics; Honoraria (self), Advisory/Consultancy: Bayer; Advisory/Consultancy: Aduro Biotech; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: 7 Hills Pharma; Licensing/Royalties: Antibodies that bind to MHC class I polypeptide-related sequence a Patent number: 10106611; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Torque Pharmaceuticals; Licensing/Royalties: Anti-Galectin Antibody Biomarkers Predictive of Anti-Immune Checkpoint And Anti-Angiogenesis Responses Publication number: 20170343552; Honoraria (self), Advisory/Consultancy: Kairos Pharma; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Bicara Therapeutics; Honoraria (self), Advisory/Consultancy: Psioxus Therapeutics; Honoraria (self), Advisory/Consultancy: Pieris Pharmaceuticals; Licensing/Royalties: Methods for Treating MICA-Related Disorders (#20100111973); Research grant/Funding (institution), Licensing/Royalties: Tumour antigens and uses thereof (#7250291); Research grant/Funding (institution): Angiopoiten-2 Biomarkers Predictive of Anti-immune checkpoint response (#20170248603); Research grant/Funding (institution), Licensing/Royalties: Compositions and Methods for Identification, Assessment, Prevention, and Treatment of Melanoma using PD-L1 Isoforms (#20160340407); Research grant/Funding (institution), Licensing/Royalties: Therapeutic peptides (#20160046716); Licensing/Royalties: Therapeutic Peptides (#20140004112); Licensing/Royalties: Therapeutic Peptides (#20170022275); Licensing/Royalties: Therapeutic Peptides (#20170008962); Advisory/Consultancy, Shareholder/Stockholder/Stock options: Pionyr Immunotherapeutics. C. Lebbé: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre Group. J-J. Grob: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy: Roche; Advisory/Consultancy: Amgen Inc.; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: Merck & Co., Inc.; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi. K. Grossmann: Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Prometheus Biosciences; Advisory/Consultancy: Roche/Genentech. J. Wagstaff: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb Company. J. Chesney: Research grant/Funding (institution): Bristol-Myers Squibb Company. M.O. Butler: Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc.; Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Adaptimmune Therapeutics plc; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Immunocore, Ltd.; Advisory/Consultancy: EMD Serono. I. Márquez-Rodas: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb Company; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre Group; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Incyte; Advisory/Consultancy: Merck Sorono; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bioncotech Therapeutics. A.C. Pavlick: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb Company; Advisory/Consultancy, Research grant/Funding (institution): Regeneron; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Jounce Therapeutics; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Merck & Co., Inc.; Research grant/Funding (institution): Replimune Group Inc.; Research grant/Funding (institution): Iovance Biotherapeutics. S. Re: Full/Part-time employment: Bristol-Myers Squibb Company. M.A. Postow: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb Company; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc.; Advisory/Consultancy, Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Incyte; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: Aduro Biotech; Research grant/Funding (institution): RGenix; Research grant/Funding (institution): Infinity Pharmaceuticals; Research grant/Funding (institution): AstraZeneca. P.A. Ascierto: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb Company; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre Fabre Group; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: Genmab; Advisory/Consultancy: Incyte; Advisory/Consultancy: MedImmune LLC; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Syndax Pharmaceuticals, Inc.; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Idera Pharmaceuticals; Advisory/Consultancy: Ultimovacs; Advisory/Consultancy: Sandoz International; Advisory/Consultancy: Immunocore, Ltd.; Advisory/Consultancy: 4SC; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Italfarmaco SpA; Advisory/Consultancy: Nektar; Advisory/Consultancy: Boehringer-Ingelheim; Travel/Accommodation/Expenses: Merck & Co., Inc. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

1083MO - Final results from ILLUMINATE-204, a phase I/II trial of intratumoral tilsotolimod in combination with ipilimumab in PD-1 inhibitor refractory advanced melanoma

Presentation Number
1083MO
Speakers
  • Cara Haymaker (Houston, TX, United States of America)

Abstract

Background

Tilsotolimod (IMO-2125), an investigational Toll-like receptor 9 agonist, activates innate and adaptive immune responses and rapidly upregulates Type I IFN and dendritic cell activation following intratumoral injection. ILLUMINATE-204 was a phase 1/2 study of tilsotolimod with ipilimumab in patients with advanced melanoma following progression on or after anti-PD-1 therapy.

Methods

Adults with unresectable or metastatic melanoma that progressed on or after a PD-1 inhibitor, an accessible tumor for intratumoral administration of tilsotolimod, and ≤ 2 lines of prior therapy (≤ 3 if BRAF-mutant) were eligible. Prior ipilimumab was allowed. Tilsotolimod was administered to a single tumor during weeks 1, 2, 3, 5, 8, and 11; ipilimumab was administered per the product label. The primary objective of the phase II portion was to assess preliminary clinical activity at the recommended phase II dose (RP2D).

Results

A total of 62 patients were treated with tilsotolimod in combination with ipilimumab. Of these, 52 received the RP2D of 8 mg, and 49 were evaluable for efficacy. The median OS was 21.0 months (95% confidence interval (CI): 9.8 - not reached [NR]), and the overall response rate per RECIST v1.1 was 22.4% (95% CI: 11.8 - 36.6), including 2 complete responses. Median duration of response was 11.4 months (95% CI: 3.3 - NR) with 7/11 responses lasting ≥ 6 months. The disease control rate was 71.4% (95% CI: 56.7 - 83.4). Tumor reduction was observed in injected and non-injected lesions. Analysis of biopsies showed rapid local IFNα gene expression, dendritic cell maturation, and expansion of shared CD8+ T cell clones in injected and non-injected tumors. Grade ≥ 3 AEs were observed in 48% (30/62) of patients, most commonly increased ALT and AST and colitis, and 26% experienced immune-related AEs. No AEs led to treatment discontinuation or death.

Conclusions

Tilsotolimod with ipilimumab was generally well-tolerated and demonstrated efficacy in anti-PD-1-refractory advanced melanoma. Activity was observed in injected and non-injected lesions. A phase III study of this combination compared with ipilimumab alone (ILLUMINATE-301; NCT03445533) is ongoing.

Clinical trial identification

NCT02644967.

Legal entity responsible for the study

Idera Pharmaceuticals.

Funding

Idera Pharmaceuticals.

Disclosure

C. Haymaker, C. Bernatchez: Advisory/Consultancy: Idera Pharmaceuticals. R.H.I. Andtbacka: Advisory/Consultancy: Aduro; Advisory/Consultancy: Merck and Co; Advisory/Consultancy: Novartis; Advisory/Consultancy: OncoSec; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takara. D.B. Johnson: Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Incyte; Advisory/Consultancy: Array Biopharma; Advisory/Consultancy: Merck and Co; Advisory/Consultancy: Novartis; Advisory/Consultancy: Janssen. S. Rahimian, S. Chunduru: Shareholder/Stockholder/Stock options, Full/Part-time employment: Idera Pharmaceuticals. I. Puzanov: Advisory/Consultancy: Amgen. J. Markowitz: Research grant/Funding (institution): Morphogenesis; Research grant/Funding (institution): Jackson Labs; Advisory/Consultancy: Newlink Genetics; Advisory/Consultancy: Array Biopharma. A. Diab: Advisory/Consultancy, Research grant/Funding (self): Idera Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (self): Nektar Therapeutics; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Novartis; Advisory/Consultancy: Array BioPharma. All other authors have declared no conflicts of interest.

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Mini Oral - Melanoma and other skin tumours Mini Oral session

Invited Discussant LBA48, 1082MO and 1083MO

Speakers
  • Ana Maria Arance Fernandez (Barcelona, Spain)