ESMO Supporter 2018

Displaying One Session

Hall A2 - Room 18 Proffered Paper session
Date
22.10.2018
Time
11:15 - 12:45
Location
Hall A2 - Room 18
Chairs
  • George Coukos (Epalinges, CH)
  • Inge M. Svane (Herlev, DK)
Proffered paper session - Immunotherapy of Cancer Proffered Paper session

DOI Session

Lecture Time
11:15 - 11:15
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45
Proffered paper session - Immunotherapy of Cancer Proffered Paper session

LBA37_PR - Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer

Presentation Number
LBA37_PR
Lecture Time
11:15 - 11:27
Speakers
  • Myriam Chalabi (Amsterdam, NL)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45

Abstract

Background

Programmed death 1 (PD-1) and CTLA-4 blockade demonstrated durable clinical benefit in patients with advanced mismatch repair deficient (dMMR) colorectal cancer. This is the first neoadjuvant study to test ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD1) in early stage dMMR and MMR proficient (pMMR) colon cancers (CC).

Methods

Patients with resectable, early stage CC received ipilimumab 1mg/kg on day (D)1 and nivolumab 3mg/kg on D1+15. Surgery was planned a maximum of 6 weeks after informed consent. Primary endpoints were safety and feasibility. Secondary endpoints included: efficacy assessed by pathological response criteria, and associations between response and tumor mutational burden (TMB), interferon (IFN)gene signatures, T-cell infiltration and T-cell receptor (TCR) clonality.

Results

So far, 14 patients with either pMMR (n=8) or dMMR (n=7) tumors were treated. Treatment was well-tolerated and all patients underwent radical resection of 15 tumors without delays in surgery. Major pathological responses (<5% viable tumor cells) were observed in 7/7 (100%) dMMR CC, with 4/7 (57%) complete responses. Four of these dMMR tumors were clinically stage IIIB/C before start of treatment. Even though no major pathological responses were seen in pMMR tumors, significant increases in T-cell infiltration, particularly CD8+ T-cells, were seen post-treatment in both pMMR and dMMR tumors, with a median fold change of 2.4 (p=0.018) and 4.8 (p=0.0009), respectively.

Strikingly, in spite of the major difference in TMB between dMMR and pMMR tumors (p=0.008), pre-treatment TCR clonality and IFN gene signatures did not differ substantially between these tumors. In contrast, post-treatment IFN signatures increased the ability to distinguish responders (dMMR) from non-responders (pMMR).

Conclusions

Short-term, neoadjuvant ipilimumab plus nivolumab resulted in major pathological responses in 100% of dMMR tumors and did not compromise surgery. While dMMR status and TMB were associated with response, pre-treatment measures of tumor inflammation may have limited predictive value. Our data suggest that neoadjuvant immunotherapy in dMMR CC warrants further research and has the potential to change the current standard of care.

Clinical trial identification

NCT03026140

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Proffered paper session - Immunotherapy of Cancer Proffered Paper session

1127O - A Personal Neoantigen Vaccine, NEO-PV-01, with anti-PD1 Induces Broad De Novo Anti-Tumor Immunity in Patients with Metastatic Melanoma, NSCLC, and Bladder Cancer

Presentation Number
1127O
Lecture Time
11:27 - 11:39
Speakers
  • Patrick A. Ott (Boston, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45

Abstract

Background

Neoantigens arise from DNA mutations in cancer cells and are important targets for T cells. Adjuvant therapy with a personal neoantigen vaccine induced T cell responses in melanoma (mel) patients and suggested synergy with anti-PD1 mAbs (Ott et al, Nature 2017). NEO-PV-01 is a personal neoantigen vaccine of up to 20 peptides (14-35 amino acids) designed based on bioinformatic analysis of a patient’s neoantigen and HLA profile. We report clinical and immune data of NEO-PV-01 in combination with nivolumab (nivo) in metastatic cancer.

Methods

NT-001 is a single-arm, phase 1b study of NEO-PV-01 with nivo in advanced mel, NSCLC, or bladder cancer. Patients begin nivo at Week 0 and at Week 12 receive NEO-PV-01 vaccine plus adjuvant Poly-ICLC in a prime-boost format. The primary endpoint is safety; secondary endpoints include overall response rate (ORR) and response conversion rate. Comprehensive immune assessments are performed throughout with biopsies at Weeks 0, 12 and 24.

Results

31 patients received at least one vaccination by the data cut and 19 had completed the full vaccine course. Vaccine-related AEs were mild (e.g., grade 1/2 injection site reactions and flu-like symptoms), with no vaccine-related SAEs. For post vaccination patients, the ORR was 52.6% (n = 10), with 2 mel and 1 NSCLC patient having response conversions. 13 patients remain on treatment (11 mel, 1 NSCLC, 1 bladder). Immune analysis was completed on 9 patients (including all 3 tumor types). Ex vivo neoantigen-specific CD4 and CD8 T cell responses against >60% of vaccine peptides were polyfunctional and of a memory phenotype. Epitope spreading post-vaccination (T cell responses to neoantigens not in the vaccine but in the patient’s tumor) was observed in 4 of 6 patients analyzed. In a subset of patients, pathologic review of pre- vs post-vaccine biopsies showed decreased tumor cellularity following vaccination.

Conclusions

Treatment with NEO-PV-01 and nivo has minimal toxicity and promising clinical activity. NEO-PV-01 is effective in inducing broad de novo neoantigen-specific immune responses in patients with metastatic cancers.

Clinical trial identification

NCT02897765.

Legal entity responsible for the study

Neon Therapeutics, Inc.

Funding

Neon Therapeutics, Inc.

Disclosure

P.A. Ott: Consulting: Neon, BMS, Merck, Novartis, Pfizer, Roche/Genentech, Celldex, CytomX. R. Govindan: Consulting and honorarium: Genentech; Advisory board: Genentech, Pfizer, Nektar, Inivata, NeoHealth, BMS. A. Naing: Research funding: NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor, Amplimmune, Armo Biosciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Baxter (spouse). T.W. Friedlander: Advisory board: Genetech, Pfizer, AstraZeneca; Research funding: Novartis, Incyte, Janssen. J.J. Lin: Honorarium: Chugai, Boehringer-Ingelheim. N. Bhardwaj: Advisory board: Neon Therapeutics, Inc. M.D. Hellman: Advisory board: Genentech/Roche, BMS, AstraZeneca, Merck, Janssen, Norvartis, Mirati, Shattuck Labs; Research support: BMS. L. Srinivasan, J. Greshock, M. Moles, R.B. Gaynor, M.J. Goldstein: Employee: Neon Therapeutics, Inc. S. Hu-Lieskovan: Consulting: Amgen, Merck, Genmab, Xencor; Research support: BMS, Merck, Vaccinex. All other authors have declared no conflicts of interest.

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Proffered paper session - Immunotherapy of Cancer Proffered Paper session

Invited Discussant LBA37_PR and 1127O

Lecture Time
11:39 - 11:54
Speakers
  • George Coukos (Epalinges, CH)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45
Proffered paper session - Immunotherapy of Cancer Proffered Paper session

1128O - Pre-specified interim analysis of a randomized phase 2b trial of trastuzumab + nelipeptimut-S (NeuVax) vs trastuzumab for the prevention of recurrence demonstrates benefit in triple negative (HER2 low-expressing) breast cancer patients

Presentation Number
1128O
Lecture Time
11:54 - 12:06
Speakers
  • Daine F. Hale (San Antonio, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45

Abstract

Background

HER2 low-expressing (LE) (IHC 1-2+, non-amplified) breast cancer (BCa) patients (pts) are not eligible for HER2-targeted therapies as confirmed in the recent NSABP B-47 trial. We have shown the HER2-derived nelipeptimut-S (E75) + GM-CSF (NeuVax) is safe, immunogenic, & acts synergistically with trastuzumab (Tz) in pre-clinical & pilot clinical studies. Here, we present the interim analysis (IA) of a multi-center, prospective, randomized, single-blinded, placebo-controlled phase 2b trial of Tz + NeuVax vs Tz to reduce recurrence in HER2 LE, node positive (NP) and/or triple negative BCa (TNBC) pts.

Methods

Pts were randomized to receive Tz & NeuVax (vaccine group; VG) or Tz + GM-CSF (control group; CG). All pts received 1 year of Tz per label. NeuVax or GM-CSF was given Q3wk x 6 starting with 3rd Tz dose, then boosted Q6mo x 4. Cardiac ejection fraction (EF) was measured at baseline and serially on study. Pre-specified IA was triggered 6 mo after last enrollment. Analyses populations were intention-to- treat (ITT) & modified ITT/safety (mITT/S) (pts receiving ≥1 dose of NeuVax or GM-CSF). The primary endpoint is disease-free survival (DFS) at 24 mo evaluated by log-rank.

Results

275 pts were enrolled (VG n = 136, CG n = 139). No significant clinicopathologic differences were seen between groups. There was no difference between groups in related local (p = 0.19) or systemic (p = 0.85) toxicities (no grade 4/5 events) or in EF pre- to post-treatment (p = 0.60). At a median follow-up of 19.4 mo, estimated (est) 24 mo DFS in the VG vs CG was 88.6% vs 82.5% in ITT (p = 0.26, HR = 0.67) and 89.3% vs 82.3% in mITT/S (p = 0.17, HR = 0.61). In NP pts, est 24mo DFS in ITT VG vs CG was 85.9% vs 80.2% (p = 0.38, HR = 0.71), but in TNBC pts, it was 91.1% vs 69.9% (p = 0.02, HR = 0.26).

Conclusions

NeuVax + Tz is safe without added cardiac toxicity compared to Tz alone. The pre-specified IA shows efficacy trends overall in favor of the NeuVax + Tz combination, but most importantly demonstrates a highly significant clinical benefit in TNBC pts, suggesting the need for a definitive Ph3 study in this underserved pt population.

Clinical trial identification

NCT01570036.

Legal entity responsible for the study

George E. Peoples; Cancer Insight, LLC.

Funding

Sellas Life Sciences Group.

Disclosure

G.E. Peoples: NeuVax inventor rights. All other authors have declared no conflicts of interest.

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Proffered paper session - Immunotherapy of Cancer Proffered Paper session

1129O - Stage 2 enrollment complete: Sitravatinib in Combination with Nivolumab in NSCLC Patients Progressing on Prior Checkpoint Inhibitor Therapy

Presentation Number
1129O
Lecture Time
12:06 - 12:18
Speakers
  • Ticiana A. Leal (Madison, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45

Abstract

Background

Sitravatinib is a spectrum-selective TKI which targets TAM receptors (Axl, MER), split family receptors (VEGFR2 and KIT), and MET. Inhibition of these receptor tyrosine kinases may enhance antitumor activity by reducing Type 2 tumor-associated macrophages, regulatory T cells and myeloid-derived suppressor cells and enhancing a T cell-mediated anti-tumor immune response. Thus, this combination is a rational approach to enhancing or restoring the clinical activity of checkpoint inhibitor therapy (CIT) in pts with immunotherapy resistant NSCLC.

Methods

Study objectives include evaluation of safety and efficacy in pts with non-squamous NSCLC who have progression of disease (PD) on or after treatment with CIT. Sitravatinib is administered orally in continuous 28-Day cycles; nivolumab is administered via IV, 240 mg every 2 weeks. Treatment arms are stratified by prior clinical benefit (PCB) vs no prior clinical benefit (NPCB [PD in ≤ 12 weeks]). A predictive probability design is used for assessment of enrollment expansion in each stage. Other objectives include PK and correlative biomarkers.

Results

Enrollment in Stage 2 of the CIT-experienced cohorts is complete and enrollment is ongoing. As of April 13, 2018, the CIT-experienced cohorts enrolled 46 pts and 25/46 have had at least one on-study tumor assessment. Twenty-one out of 25 pts have demonstrated tumor reductions. Seven pts out of the 25 have achieved a partial response (PR); 4 confirmed and 3 unconfirmed (1 PR/3 uPR in PCB; 3 PRs in NPCB cohorts, respectively); with the longest treatment duration exceeding 50 weeks. Sitravatinib-related AEs (>10% of pts; all grades) included diarrhea, nausea, vomiting, decreased appetite, fatigue, mucosal inflammation, dysphonia, AST/ALT increase, weight decrease, hypertension, and palmar-plantar erythrodysaesthesia syndrome. Updated safety and efficacy data will be presented.

Conclusions

The combination of sitravatinib with nivolumab is clinically active with manageable side effects. Correlation of clinical activity with molecular analyses, including specific gene alterations and tumor mutation burden, is underway and will be presented.

Clinical trial identification

NCT02954991.

Legal entity responsible for the study

Mirati Therapeutics, Inc.

Funding

Mirati Therapeutics, Inc.

Disclosure

T.A. Leal: Advisory board (consulting): Takeda, AstraZeneca, Novartis, AbbVie, BMS. A.I. Spira: Consulting and research support (to institution): Mirati Therapeutics. C. Blakely: Research funding: Mirati, Novartis, Ignyta, Medimmune, Clovis; Consulting: Jazz Pharmaceuticals. E. Massarelli: Speakers bureau: AstraZeneca, Merck; Consultant: Genetech; Grants and research support: BMS, Genetech, I. Chen: Employment: Mirati Therapeutics. J. Christensen, P. Olson: Employment and stock ownership: Mirati Therapeutics. V. Tassell: Employment and stock ownership: Mirati Therapeutics; Stock ownership: Pfizer. L. Horn: Consulting: Abbvie, AstraZeneca, BMS, Genentech, Merck, Incyte, Xcovery. All other authors have declared no conflicts of interest.

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Proffered paper session - Immunotherapy of Cancer Proffered Paper session

1130O - Responses and Durability of Clinical Benefit in Renal Cell Carcinoma Treated with Pegilodecakin in Combination With Anti-PD-1 Inhibitors

Presentation Number
1130O
Lecture Time
12:18 - 12:30
Speakers
  • Aung Naing (Houston, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45

Abstract

Background

Pegilodecakin (AM0010) is a pegylated recombinant human interleukin-10 that stimulates activation, survival and clonal expansion of intra-tumoral, tumor antigen specific CD8+ T cells. Pegilodecakin also up-regulates IFNγ and the expression of MHC, which enables tumor antigen presentation in neoplasias of low mutational burden and promotes immunosurveillance by expanding effector memory T cells (Mumm et al. 2010, 2011). Finally, pegilodecakin reduces tumor inflammatory processes such as angiogenesis and and metastatic dissemination (Oft 2017), the off-target auto-immune side effects of immunotherapy and the inflammatory-related side effects of some chemotherapies.

Methods

In a 353 patient phase 1/1b dose escalation and expansion study conducted in the US from 2013 to 2017, 37 pretreated RCC subjects received pegilodecakin with pembrolizumab or nivolumab. Responses were assessed by irRC.

Results

TrAE were reversible and transient. G 3/4 TrAE in pts who received pegilodecakin (20 ug/kg) + nivo or pembro included anemia (10), thrombocytopenia (7) and hypertriglyceridemia (6). Pts on 10 ug/kg pegilodecakin + nivo or pembro did not have G3/4 anemia or thrombocytopenia.

PegilodecakinNPrior TherapiesORRDCRmPFSmOSOne-YearirAE6irAE6
RegimenE (ITT)5Median (Range)%%mosmosOS (%)All Grades (%)Grades 3 & 4 (%)
Monotherapy116 (19)3 (0-7)25.056.01.99.8-5.30.0
Plus Pembrolizumab28 (8)2 (0-5)50.010016.7NR88.0--
Plus Nivolumab326 (29)1 (0-5)39.081.010.1NR89.0--
Pooled Plus Anti-PD-1434 (37)2 (0-5)41.085.012.5NR89.016.25.4

20µg/kg QD, SC;

2mg/kg, q3wk IV;

3mg/kg, q2wk IV;

pembrolizumab and nivolumab cohorts combined;

E (evaluable - baseline tumor assessment + >1 post-baseline assessments, and no major protocol deviations); ITT (intent to treat);

irAE - Immune-Related Adverse Events (e.g. pneumonitis, adrenal insufficiency, thyroiditis, hypothyroiditis, hypophysitis, mucositis/stomatis, colitis, hepatitis, cholangitis, polyarthritis, myasthenia gravis, optic neuritis); Data cut on 05.01.18; Median follow-up for pembrolizumab cohort 34.6 months (12.3-36.2 months); Median follow-up for nivolumab cohort 18.9 months (0.5-25.9 months)

Conclusions

Pegilodecakin when combined with anti-PD-1 therapy in advanced RCC patients was associated with response rates and durability of benefit greater than has been seen with anti-PD-1 alone. These preliminary findings support further studies of pegilodecakin with anti-PD-1 therapies.

Clinical trial identification

NCT02009449.

Legal entity responsible for the study

ARMO BioSciences.

Funding

ARMO BioSciences.

Disclosure

A. Hung, M. Oft, J. Leveque: Employee: ARMO BioSciences. All other authors have declared no conflicts of interest.

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Proffered paper session - Immunotherapy of Cancer Proffered Paper session

Invited Discussant 1128O, 1129O and 1130O

Lecture Time
12:30 - 12:45
Speakers
  • Dirk Jäger (Heidelberg, DE)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
11:15 - 12:45