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Displaying One Session

Mini Oral session
Date
18.09.2020
Chairs
  • Fiona Thistlethwaite (Manchester, United Kingdom)
  • Inge-Marie Svane (Herlev, Denmark)
  • Pedro Romero (Epalinges, Switzerland)
Mini Oral - Investigational immunotherapy Mini Oral session

Open & welcome

Speakers
  • Fiona Thistlethwaite (Manchester, United Kingdom)
Mini Oral - Investigational immunotherapy Mini Oral session

1022MO - Clinical potential of adoptive cell therapy with tumour infiltrating lymphocytes therapy in combination with checkpoint inhibitors in non-melanoma patients

Presentation Number
1022MO
Speakers
  • Anders H. Kverneland (Herlev, Denmark)

Abstract

Background

The effect of adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) has repeatedly been demonstrated in malignant melanoma and recent studies have indicated a potential in other selected cancer diagnoses. In a clinical trial (NCT03296137) we have tested the potential of TIL-based ACT across cancer types.

Methods

Twenty-five patients with 12 different cancer diagnoses were treated with ex vivo expanded TILs at Herlev University Hospital between 2017 and 2019. The ACT was preceded by a single dose of ipilimumab before tumor removal and combined with 4 doses of nivolumab before and after cell infusion. Patients were hospitalized for conditioning chemotherapy before T cell infusion followed by 14 days of low-dose interleukin-2 (IL-2).

Results

Four patients (16%) - 2 with head-and-neck cancer, 1 cholangiocarcinoma and 1 sarcoma – obtained a partial response to therapy, 17 patients stabile disease and 4 progressive disease. Median progression-free survival was 88 days. Overall, the therapy regimen was tolerated and safe in all patients with expected side effects comparable to malignant melanoma ACT TIL trials but with the addition of immune related adverse events from the checkpoint inhibitors. The ex vivo expansion of TILs was successful in 30/31 recruited patients across cancer types with a median expansion time of 24 days. In-depth immune phenotyping of the TILs both in the tumor and after ex vivo expansion along with ex vivo anti-tumor reactivity will be presented.

Conclusions

Our data show that TIL-based ACT in combination with checkpoint inhibitors is safe and feasible. We show that clinical responses can be obtained in previously unreported cancer types and confirm that TIL-therapy has a potential in non-melanoma patients.

Clinical trial identification

NCT03296137.

Legal entity responsible for the study

The authors.

Funding

Danish Cancer Society, Knæk Cancer.

Disclosure

All authors have declared no conflicts of interest.

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Mini Oral - Investigational immunotherapy Mini Oral session

1027MO - ALKS 4230 monotherapy and in combination with pembrolizumab (pembro) in patients (pts) with refractory solid tumours (ARTISTRY-1)

Presentation Number
1027MO
Speakers
  • Ulka N. Vaishampayan (Ann Arbor, United States of America)

Abstract

Background

ALKS 4230 is a fusion protein of circularly permuted interleukin-2 (IL-2) & IL-2Rα designed to selectively bind to the intermediate-affinity IL-2 receptor. ALKS 4230 is being investigated as monotherapy & in combination with pembro in pts with solid tumors. We report extended follow-up from combination therapy and new ALKS 4230 monotherapy data.

Methods

ARTISTRY-1 (NCT02799095) is an ongoing 3-part phase I/II study. In Parts A (dose escalation) and B (expansion), ALKS 4230 is administered as IV monotherapy on days 1-5 of 14- or 21-day cycles. In Part C (combination therapy), ALKS 4230 is administered via the same 5-day regimen q21d with pembro on day 1. Outcomes presented include safety, PK/pharmacodynamics, RP2D, and antitumor activity (RECIST v1.1 & iRECIST) from Parts B & C (response data cut: 4/29/2020; all other data: 3/23/2020).

Results

In Part B, 9 pts (5 melanoma, 4 RCC) received 6 μg/kg (RP2D). The most common adverse events (AEs) were grade ≤2 (fevers, chills, hypotension [not requiring vasopressors]). No treatment-related deaths occurred; no AEs led to treatment discontinuation. One pt with metastatic urethral melanoma (which had previously recurred following adjuvant nivolumab) achieved partial response (PR) to 6 μg/kg ALKS 4230 monotherapy with normalization of serum LDH. In Part C, 46 pts (13 tumor types) received ALKS 4230 (3 μg/kg) and pembro. The most common tumor types (≥5 each) were colorectal, ovarian (OC), & sarcoma. Addition of pembro did not alter the PK/pharmacodynamics of ALKS 4230; no new toxicities were observed. Among pts with ≥1 scan, 1 heavily pretreated pt with OC achieved complete response (per RECIST) & continues therapy >12 months; PR was seen in 2 other OC pts (1 pt awaiting confirmatory scan) who received therapy for 7 & 3 months, respectively, both ongoing; iPR was seen in 1 pt with triple-negative breast cancer (on therapy >12 months). All 4 responders were checkpoint inhibitor naive.

Conclusions

ALKS 4230 is a promising novel agent given its tolerability & efficacy profile, which includes single agent activity & durable responses even in a pretreated pt population. Future research of mono & combination therapy with ALKS 4230 is warranted.

Clinical trial identification

NCT02799095.

Editorial acknowledgement

Medical writing and editorial support was provided by Parexel and funded by Alkermes, Inc.

Legal entity responsible for the study

Alkermes, Inc.

Funding

Alkermes, Inc.

Disclosure

U.N. Vaishampayan: Honoraria (self), Advisory/Consultancy: Alkermes; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Merck. V. Velcheti: Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: EMD Serono. C.J. Hoimes: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astellas; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Merck; Research grant/Funding (institution): 2bPrecise. A. Spreafico: Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Oncorus; Advisory/Consultancy: Janssen; Research grant/Funding (self): Symphogen; Research grant/Funding (self): AstraZeneca/MedImmune; Research grant/Funding (self): Bayer; Research grant/Funding (self): Surface Oncology; Research grant/Funding (self): Northern Biologics; Research grant/Funding (self): Janssen Oncology/J&J; Research grant/Funding (self): Roche; Research grant/Funding (self): Regeneron; Research grant/Funding (self): Alkermes; Research grant/Funding (self): Array Biopharma. D.F. McDermott: Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Alkermes; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Iovance; Advisory/Consultancy: Eisai; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): X4 Pharma; Leadership role: GU Committee Eastern Cooperative Oncology Group; Leadership role: Renal Cell Carcinoma Task Force, National Cancer Institute; Leadership role: Melanoma Breakthrough Consortium Melanoma Research Foundation; Leadership role: Cancer Immunotherapy Guidelines Kidney Task Force Society for Immunotherapy of Cancer. Q.S-C. Chu: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BI; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Officer/Board of Directors: Epizyme; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Debio; Research grant/Funding (institution): Esperas; Research grant/Funding (institution): Exactis; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): Takeda and TP Therapeutics; Leadership role: IND Committee and Lung Committee of Canadian Clinical Trials Group; Non-remunerated activity/ies: Canadian Mesothelioma Foundation; Non-remunerated activity/ies: Princess Margaret Cancer Centre; Leadership role: Merck KGaA. L. Gilbert: Full/Part-time employment: Synoes; Research grant/Funding (self): Alkermes. H. Hirte: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): BI; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Immunogen; Research grant/Funding (institution): Immunovac; Research grant/Funding (institution): Alkermes; Leadership role: Canadian Cancer Trials Group (CCTG) - Gynecologic Disease Site Committee; Leadership role: Gynecologic Oncologists of Canada (GOC); Leadership role: Canadian Association of Medical Oncologists (CAMO). K.K. Curtis: Full/Part-time employment: Synoes; Research grant/Funding (self): Alkermes. Y. Du: Full/Part-time employment: Alkermes, Inc. I. Bidollari: Shareholder/Stockholder/Stock options, Full/Part-time employment: Alkermes, Inc.; Shareholder/Stockholder/Stock options, Full/Part-time employment: Teva; Full/Part-time employment: Novartis. L. Sun, E. Putiri, B. Dezube: Shareholder/Stockholder/Stock options, Full/Part-time employment: Alkermes, Inc. H.C. Losey: Shareholder/Stockholder/Stock options, Full/Part-time employment: Alkermes, Inc.; Shareholder/Stockholder/Stock options: BMS. M.S. Ernstoff: Honoraria (self), Advisory/Consultancy, Leadership role, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Alkermes; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): EMD Serono; Advisory/Consultancy: ImmuNext; Advisory/Consultancy: OmniSeq. All other authors have declared no conflicts of interest.

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Mini Oral - Investigational immunotherapy Mini Oral session

Invited Discussant 1022MO and 1027MO

Speakers
  • Fiona Thistlethwaite (Manchester, United Kingdom)
Mini Oral - Investigational immunotherapy Mini Oral session

LBA42 - POD1UM-202: Phase II study of retifanlimab in patients (pts) with squamous carcinoma of the anal canal (SCAC) who progressed following platinum-based chemotherapy

Presentation Number
LBA42
Speakers
  • Sheela Rao (London, United Kingdom)

Abstract

Background

Effective salvage treatment for advanced SCAC has not been established; however, checkpoint immunotherapy shows promise. Retifanlimab (INCMGA00012), a humanized IgG4 monoclonal antibody that recognizes human programmed cell death protein 1 (PD-1), has demonstrated activity and tolerability across a broad range of solid tumors. POD1UM-202 was designed to evaluate retifanlimab in pts with previously treated advanced SCAC.

Methods

Phase II, single-arm study in pts 18 years or older with progression following standard therapy and RECIST measurable disease. Prior immunotherapy was not allowed. Pts with well-controlled human immunodeficiency virus (HIV) infection were eligible. Retifanlimab was administered intravenously at 500 mg every 4 weeks. The primary study endpoint was overall response rate (ORR) assessed by independent central review (ICR) per RECIST v1.1.

Results

94 pts were enrolled with median age of 64 years, most were female (64.9%) and white (76.6%), and had an ECOG PS of 0 (41.5%) or 1 (58.5%). 73.4% had received prior CRT, 17% RT alone, and 97% had received platinum. Liver metastasis was reported in 39 (41.5%) pts and 9 (9.6%) were known to be HIV-positive. Median (range) duration of follow-up was 7 (<1–19) months. ICR confirmed responses were reported in 13 (13.8%) pts (1 complete response; 12 partial responses) and 33 (35.1%) pts had stable disease; median (range) DOR was 9.5 (5.6–not estimable) months. Responses were observed regardless of PD-L1 expression, liver metastases, or HIV-positive status. Median (95% CI) PFS and OS were 2.3 (1.9–3.6) and 10.1 (7.9–NE) months, respectively. Responses were associated with marked prolongation of PFS and OS. Retifanlimab was well-tolerated, including in the HIV-positive population, with a safety profile as expected for a PD-1 inhibitor and a low incidence of treatment discontinuation due to immune-related adverse events (2.1%).

Conclusions

Results from this large phase 2 trial demonstrate encouraging efficacy and an acceptable safety profile with retifanlimab in pts with previously treated advanced or metastatic SCAC, including pts with well-controlled HIV infection.

Clinical trial identification

NCT03597295 (July 24, 2018); EudraCT: 2018-002070-51 (2018-11-14).

Editorial acknowledgement

Editorial assistance was provided by Kakuri Omari of Envision Pharma Group (Philadelphia, PA, USA).

Legal entity responsible for the study

Incyte Corporation.

Funding

Incyte Corporation.

Disclosure

S. Rao: Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy, Non-remunerated activity/ies: Bayer; Honoraria (institution), Advisory/Consultancy, Non-remunerated activity/ies: Celgene; Honoraria (institution), Advisory/Consultancy: Shire; Non-remunerated activity/ies: Incyte. J. Capdevila: Advisory/Consultancy, Research grant/Funding (institution): Advanced Accelerator Applications; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Sanofi. S. Kim: Research grant/Funding (institution): Bioproject Pharma; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Servier; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Ipsen; Honoraria (institution), Advisory/Consultancy: MSD. L. Dahan: Honoraria (institution): Amgen; Honoraria (institution): Sanofi; Honoraria (institution): Servier. M. Fakih: Advisory/Consultancy: Taiho; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Speaker Bureau/Expert testimony: Guardant; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis. L.H. Jensen: Research grant/Funding (institution): 2cureX; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): MSD. K-L.G. Spindler: Honoraria (institution), Non-remunerated activity/ies: Amgen; Honoraria (institution), Non-remunerated activity/ies: Merck Serono; Honoraria (institution), Non-remunerated activity/ies: Nordic Drugs BV; Honoraria (institution), Non-remunerated activity/ies: Roche/Genentech. D. Arnold: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Servier; Honoraria (institution), Advisory/Consultancy: Terumo; Advisory/Consultancy: Biocompatibles; Advisory/Consultancy: Helsinn Therapeutics; Advisory/Consultancy: Roche; Research grant/Funding (institution): Sanofi. M. Cornfeld: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. M. Jones: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. C. Tian: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. M. Catlett: Shareholder/Stockholder/Stock options, Full/Part-time employment: Incyte. J-P. Spano: Honoraria (institution): AstraZeneca; Honoraria (institution), Advisory/Consultancy: Biogaran; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Gilead Sciences; Honoraria (institution): Leo Pharma; Honoraria (institution): Lilly; Honoraria (institution): Mylan; Honoraria (institution): Myriad Genetics; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Pierre Fabre; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.

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Mini Oral - Investigational immunotherapy Mini Oral session

1023MO - AMC 095: A report of nivolumab (nivo) in advanced HIV associated solid tumours (ST)

Presentation Number
1023MO
Speakers
  • Lakshmi Rajdev (New York, United States of America)

Abstract

Background

Immune checkpoint blockade has emerged as a therapeutic strategy for cancers. The objective of this phase I study was to evaluate the safety/tolerability and describe immune-mediated effects of nivo in patients (pts) with HIV-associated ST.

Methods

Pts received nivo at 3 mg/kg q 2 wk, in two dose de-escalation cohorts stratified by CD4 count (Stratum 1: CD4 counts>200/uL and Stratum 2: CD4 count 100-200/uL) in pts with ST. An expansion cohort of 24 patients with CD4 count > 200 was then enrolled.

Results

A total of 37 pts were treated with nivo (n=4, 9, 24 for strata 1/2 and expansion cohorts). Histologies included Kaposi Sarcoma [KS](n=15), anal cancer [ca](n=5), lung ca (n=4) and other ST (n=13). No pts experienced dose-limiting toxicities (evaluable n=3 [stratum 1] and n=6 [stratum 2]). Treatment-related adverse events (AEs) were experienced by 14 (38%) pts. The most common treatment-related AEs were fatigue (n=5) and maculo-papular rash (n=4); of which, grade 3/4 severity was experienced by 2 pts each. Objective response rate (RR) by modified WHO criteria was 24% (9/37); with partial response (PR) in pts with KS (n=5), anal ca (n=1), colon ca (n=1), adenocarcinoma of the gall bladder (n=1), and squamous cell ca (n=1). There were no significant changes detected in HIV viral load (VL) during the study, which was undetectable for 97% of participants at baseline. Baseline median absolute CD4 was 315 (IQR, 225-434), and there was a trend for a reduction at 6-week (wk) post-treatment follow-up [f/u] (median difference: -35 (IQR, -83 to 37), p=0.072). Median CD4/CD8 ratio at baseline was 0.41 (IQR, 0.33-0.75) and increased by a median of 0.10 (IQR, -0.05 to 0.14, p=0.060) and 0.08 (IQR, 0 to 0.18, p=0.021) at 6- and 16 wk post-treatment f/u.

Conclusions

Nivo has acceptable safety in HIV patients with ST. Plasma viremia remained suppressed during the study suggesting no viral reactivation, and CD4/CD8 count ratio was increased at 16 wk post-treatment. A RR of 24% was observed in tumors known to be responsive to ICB. Thus, it is appropriate for HIV+ pts with ST treated with ART and a CD4+ T-cell count of greater than 100 cells/μL and undetectable VL to receive nivo in clinical trials and FDA-approved indications.

Clinical trial identification

NCT02408861.

Legal entity responsible for the study

AMC (AIDS Malignancy Consortium).

Funding

NCI Grant #UM1CA121947.

Disclosure

L. Rajdev: Honoraria (self), Travel/Accommodation/Expenses: Bayer Pharmaceuticals. R. Baiocchi: Honoraria (self), Advisory/Consultancy, Leadership role, Research grant/Funding (self): Prelude Tx, Viracta. C-C.J. Wang, M.S. Lee: Research grant/Funding (institution): Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

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Mini Oral - Investigational immunotherapy Mini Oral session

Invited Discussant LBA42 and 1023MO

Speakers
  • Inge-Marie Svane (Herlev, Denmark)
Mini Oral - Investigational immunotherapy Mini Oral session

1024MO - A phase I/II MATINS trial: Part 1 pharmacokinetic, safety and efficacy results of Clever-1 blockade in advanced cancer

Presentation Number
1024MO
Speakers
  • Petri Bono (Turku, Finland)

Abstract

Background

Tumor associated macrophages (TAMs) have a pro-tumorigenic, anti-inflammatory M2 phenotype and express a scavenger receptor CLEVER-1 (Stabilin-1/FEEL-1). CLEVER-1 inhibition in mice reactivates CD8+ T-cell response with a robust anti-tumor activity. FP-1305 is a novel IgG4-antibody targeting CLEVER-1 and induces a phenotypic M2 to M1 immune switch of TAMs.

Methods

MATINS (Macrophage Antibody To INhibit immune Suppression) trial is a three-part, first-in-human phase I/II study (NCT03733990) to assess the safety and preliminary efficacy of FP-1305 in patients with advanced solid tumours. The Part I has been completed. In Part II, 110 subjects with solid tumours will be enrolled for efficacy (ORR) and safety.

Results

In Part I, 30 patients were enrolled into five different dose levels (0.1 - 10 mg/kg) and received 1-8 doses (median 3) of FP-1305 q3w. FP-1305 was well tolerated without dose-limiting toxicities. 28.9 % of the treatment emergent adverse events were related to the study drug. The half-life of FP-1305 (t1/2) was 19.5 h (CV% 51.0). The disease control rate in target lesions was 27% and the overall response rate according to RECIST 1.1 was 3%. Peripheral increase in NK cells, CD4+, CD8+, CD8+/CD4+ T cells ratio, B cells and a decrease in regulatory T cells was observed after FP-1305 dosing. Also at least a 20 % increase of systemic IFNγ in 40 % of patients and CXCL10 in 33 % of patients was observed. FP-1305 dosing led to activation (CD25+) and Th1 skewing (CXCR3+) of T cell populations including increase in effector CD8 T-cell population with downregulation of several inhibitory immune checkpoint molecules (PD-1, PD-L1, CTLA-4 and LAG3). Data will be updated for PK and efficacy.

Conclusions

FP-1305 administration in advanced cancer patients can promote immune switch and peripheral lymphocyte activation alongside promising tolerability. Despite relatively short half-life, durable Th1 activation and mobilization of NK and B cells accompanied with persistent IFNγ and CXCL10 induction was observed. Despite formal progression according to RECIST, potential anti-tumour activity was noted with some target lesions showing regression or stability in several patients. Targeting Clever-1 holds promise as a novel immunotherapy.

Clinical trial identification

NCT03733990.

Legal entity responsible for the study

Faron Pharmaceuticals LTD.

Funding

Faron Pharmaceuticals LTD.

Disclosure

P. Bono, P. Jaakkola, S. Shetty, Y.T. Ma, M.J.A. de Jonge, D. Robbrecht, A.R. Minchom, A. Pal, C. Yap, A. Pasanen, T. Skytta, A. Thibault, R. Cruz, J. Koivunen: Advisory/Consultancy: Faron Pharmaceuticals. M. Jalkanen: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Faron Pharmaceuticals LTD. S. Jalkanen: Advisory/Consultancy, Spouse/Financial dependant: Faron Pharmaceuticals LTD. M. Hollmén: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Faron Pharmaceuticals LTD. J. Mandelin, M. Karvonen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Faron Pharmaceuticals LTD.

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Mini Oral - Investigational immunotherapy Mini Oral session

1025MO - First-in-human (FIH) phase I study of RO7122290 (RO), a novel FAP-targeted 4-1BB agonist, administered as single agent and in combination with atezolizumab (ATZ) to patients with advanced solid tumours

Presentation Number
1025MO
Speakers
  • Ignacio Melero (Pamplona, Spain)

Abstract

Background

RO is a bispecific antibody-like fusion protein based on a trimeric 4-1BB ligand and a targeting Fab moiety recognizing fibroblast activation protein-α (FAP) abundantly expressed by cancer-associated fibroblasts in many tumors. Upon TCR/CD3 engagement, simultaneous binding of FAP and 4-1BB results in clustering and activation of T- and NK- cells at the tumor site, thereby leading to potent anti-tumor activity in a panel of preclinical models.

Methods

This is a 3-part FIH study: Part A and B explored the safety, PK, PD and anti-tumor activity to establish the recommended dose for expansion (RDE) into Part C of RO as single agent (SA) and in combination with ATZ, respectively. Part C assesses the efficacy and safety of the combination in selected, FAP positive tumors. Preliminary results of Part A/B are presented here, where patients (pts) were treated with RO weekly (QW) at escalated dose levels (DLs).

Results

Part A: 62 pts were treated at 13 DLs, range 5 – 2000 mg IV. Part B (plus ATZ 1200 mg Q3W): 39 pts at 8 DLs, 45 – 2000 mg IV. Serum exposure (Cmax; AUC) increased dose dependently, with evidence of non-linearity in elimination at lower doses, suggestive of target-mediated drug disposition (TMDD). In blood, expression of 4-1BB and release of soluble 4-1BB indicated T-cell activation and 4-1BB targeting. Paired tumor biopsies revealed strong accumulation of CD8+Ki67+ T-cells. Adverse events (AEs) were generally mild to moderate (i.e., G1-2) across both parts. Most common AEs ≥ G3 in Part A were asthenia (6.5%), AST elevation and pneumonia (each 4.8%), whereas pneumonia, pneumonitis (each 10.3%), neutro- and lymphocytopenia (each 7.7%) were most frequent in Part B. DLTs were febrile neutropenia G3 (45 mg), CRS G3 (130 mg) and pneumonitis G3 (500 mg plus ATZ); a MTD was not reached. Objective response rates were 3.6% (A) and 18.4% (B).

Conclusions

RO demonstrated an acceptable safety profile as SA and in combination with ATZ. PK and PD- effects were favorable and consistent with the antibody-like format and the postulated MoA, respectively. Preliminary anti-tumor activity supports further exploration of the combination in tumor-specific indications.

Clinical trial identification

EUDRACT Number: 2017-003961-83; Protocol Number: BP40087.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

I. Melero: Advisory/Consultancy, Non-remunerated activity/ies: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy: Bioncotech; Advisory/Consultancy, Research grant/Funding (self): Alligator; Advisory/Consultancy: Numab; Advisory/Consultancy: F-Star; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (self): Merck Serono; Advisory/Consultancy: MSD; Advisory/Consultancy: Boston Pharmaceuticals; Advisory/Consultancy: Servier; Research grant/Funding (self): Palo Biopharma; Non-remunerated activity/ies: Roche ImCore. M.F. Sanmamed: Research grant/Funding (self): Roche. E. Calvo: Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (self), Research grant/Funding (institution): Novartis; Research grant/Funding (self): Beigne; Advisory/Consultancy, Research grant/Funding (institution): Abbvie; Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Boehringer; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Janssen Onc; Research grant/Funding (institution): Hospira; Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Merus; Advisory/Consultancy, Research grant/Funding (institution): Nanobiotix; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): OncoMed; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PharmaMed; Advisory/Consultancy, Research grant/Funding (institution): PisOxus; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): ACEA Bio; Research grant/Funding (institution): Cytomx. I. Moreno: Speaker Bureau/Expert testimony: BMS. V. Moreno: Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): E-Therapeutics; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Menarini; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Nonobiotix; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Psioxus; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Regneron; Advisory/Consultancy: Pieris; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Pieris; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Boehringer; Advisory/Consultancy: Pieris; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): E-Therapeutics; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Menarini; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Nonobiotix; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): E-Therapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Psioxus; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Regneron; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Menarini. M. Martinez-Garcia: Leadership role, Board Member: GENIO; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, Clinical Trial: Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses, Clinical Trial: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Speaker Bureau/Expert testimony: Pierre Fabre; Research grant/Funding (institution), Clinical Trial: Array Biopharma; Research grant/Funding (institution), Clinical Trial: Astellas; Research grant/Funding (institution), Clinical Trial: Immunomedics; Research grant/Funding (institution), Clinical Trial: Macrogenics; Research grant/Funding (institution), Clinical Trial: MSD; Research grant/Funding (institution), Clinical Trial: Sanofi; Research grant/Funding (institution), Clinical Trial: Novartis. A. Rodriguez-Vida: Research grant/Funding (self): MSD; Research grant/Funding (self): Takeda; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy: Astellas; Advisory/Consultancy: Janssen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Clovis; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Elisa Pharma. J. Tabernero: Advisory/Consultancy: Array; Advisory/Consultancy: AstraZeneca; Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Beigene; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Chugai; Advisory/Consultancy: Genentech; Advisory/Consultancy: Genmab; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Imugene; Advisory/Consultancy: Inflection Biosciences; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Kura; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Menarini; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Merus; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Agendia; Research grant/Funding (institution): Debiopharm; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Mologen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Symphogen. A.B. Azaro Pedrazzoli: Advisory/Consultancy: Orion Pharma; Advisory/Consultancy, Research grant/Funding (self): Amcure GmbH. I. Spanggaard: Research grant/Funding (institution): Puma Biotech; Leadership role, Board Member: Danish Society of Clin Oncol. K.S. Rohrberg: Research grant/Funding (institution): Puma; Research grant/Funding (institution), Clinical Trial: Roche; Research grant/Funding (institution), Clinical Trial: BMS; Research grant/Funding (institution), Clinical Trial: Genentech; Research grant/Funding (institution), Clinical Trial: Orion; Research grant/Funding (institution), Clinical Trial: Catargia; Research grant/Funding (institution), Clinical Trial: Pfizer; Research grant/Funding (institution), Clinical Trial: Cellgen; Research grant/Funding (institution), Clinical Trial: Loxo; Research grant/Funding (institution), Clinical Trial: Eli Lilly; Research grant/Funding (institution), Clinical Trial: Symphogen; Research grant/Funding (institution), Clinical Trial: Alligator Bioscience; Research grant/Funding (institution), Clinical Trial: Genmab; Research grant/Funding (institution), Clinical Trial: Incyte; Research grant/Funding (institution), Clinical Trial: Novartis; Research grant/Funding (institution), Clinical Trial: Amgen; Research grant/Funding (institution), Clinical Trial: Bayer. E. Guarin, M. Ceppi, U. Sweere, C. McIntyre: Full/Part-time employment: Roche. E. Nueesch, E. Chesne, O. Krieter: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. F.S. Lichtenegger: Speaker Bureau/Expert testimony, Speaker honoraria while in academia: Novartis; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche; Research grant/Funding (institution), Clinical trial funding while in academia: BMS; Research grant/Funding (institution), Research funding while in academia: Miltenyi. All other authors have declared no conflicts of interest.

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Mini Oral - Investigational immunotherapy Mini Oral session

1026MO - Phase Ib dose escalation study of novel immunogenic cell death (ICD) inducer PT-112 plus PD-L1 inhibitor avelumab in solid tumours

Presentation Number
1026MO
Speakers
  • Daniel D. Karp (Houston, TX, United States of America)

Abstract

Background

Pyrophosphate-platinum conjugate PT-112 induces ICD, recruits effector T cells, promotes immune memory and synergizes with immune checkpoint inhibitors (ICI) in murine models. This pleiotropic mechanism of action, along with durable responses to PT-112 alone in ICI non-responding pts, prompted this combination study with avelumab (“PAVE”), from which we present results of dose escalation.

Methods

A 3+3 design was used to determine the recommended phase II dose (RP2D) for PT-112 (28-day cycle IV days 1, 8, 15) with avelumab 800 mg (days 1 and 15) in pts with progressing solid tumors, with no available effective therapy (Tx). Previous ICI Tx was allowed.

Results

Across five dose cohorts (150, 200, 250, 300, and 360 mg/m2 PT-112) 36 pts were enrolled: 7 non-small cell lung, 6 urothelial, 4 breast, 3 castration-resistant prostate (CRPC), and 1 squamous head and neck, plus 15 supplemental CRPC pts enrolled at 200 mg/m2 to enhance safety and efficacy data. PAVE was well tolerated with no dose limiting toxicity. Common treatment-related adverse events (TRAEs) were nausea (47%), fatigue (31%), thrombocytopenia (28%), and decreased appetite (28%); 44% of pts had grade 3-4 TRAEs (most frequent was thrombocytopenia: 17%). The PT-112 RP2D is 360 mg/m2, as reported for PT-112 single agent. Median prior lines of systemic Tx differed for escalation pts (4) and supplemental CRPC pts (6), and modified dosing was effective in pts with limited bone-marrow reserve. Of 12 pts with measurable disease and imaging follow-up in escalation, 8 experienced stable disease (4 with prior ICI Tx). Two CRPC pts responded: one with durable improved PSA and bone metastases, PFS 11.4 months (150mg/m2, MSI stable); another with confirmed RECIST partial response (66% reduction), PSA reduction (94%), bone scan improvement, and ongoing PFS 9.5 months (200 mg/m2, PIK3CBmut and PTEN loss, prior ICI Tx). 4 of 18 total CRPC pts had reductions in PSA ≥50%; 15 of 18 in alkaline phosphatase.

Conclusions

PAVE combination Tx was feasible and well-tolerated in a heavily pre-treated population. Preliminary evidence of efficacy was observed across a range of PT-112 doses, and further investigation of the combination is ongoing in the phase IIa portion of the protocol.

Clinical trial identification

NCT03409458.

Legal entity responsible for the study

Phosplatin Therapeutics.

Funding

Phosplatin Therapeutics.

Disclosure

T.D. Ames, J.M. Jimeno: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Phosplatin Therapeutics. All other authors have declared no conflicts of interest.

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Mini Oral - Investigational immunotherapy Mini Oral session

Invited Discussant 1024MO, 1025MO and 1026MO

Speakers
  • Pedro Romero (Epalinges, Switzerland)