IFN-α / Theraclone Sciences - LARVOL DELTA

A Phase 1/2 trial of intratumoral (i.t.) IMO-2125 (IMO) in combination with checkpoint inhibitors (CPI) in PD-(L)1-refractory melanoma (ESMO 2017) - P1/2; "IMO + ipi is a viable strategy to revive the immune response in CPI-resistant tumors and shows preliminary clinical activity worthy of further development."

Checkpoint inhibition • Clinical • Combination therapy • P1/2 data • Melanoma

Single-Arm Salvage Therapy with Pegylated Interferon Alfa-2a for Patients with High-Risk Polycythemia Vera or High-Risk Essential Thrombocythemia Who Are Either Hydroxyurea-Resistant or Intolerant: Final Results of the Myeloproliferative Disorders-Research Consortium (MPD-RC) Protocol 111 Global Phase II Trial (ASH 2017) - P2; "PEG is an effective agent to treat patients with ET/PV, capable of achieving 12 month ORR in 69% and 60% of ET and PV patients, respectively. The presence of CALR at baseline was associated with superior CR rates in ET. Treatment was associated with significant numbers of AEs which can limit tolerability."

Biomarker • Clinical • P2 data • Acute Myelogenous Leukemia • Biosimilar • Depression • Fibrosis • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Venous Thromboembolism

Clonality of T cell repertoire in the tumor (TME) and peripheral blood of regionally advanced melanoma patients (pts) treated with neoadjuvant ipilimumab (ipi) and high dose interferon-α (HDI). (ASCO 2017) - P1; "Higher T cell fraction and lower clonality in PBMC when measured early on-treatment, and higher TIL fraction in primary tumor constituted promising biomarkers of response. Pts with higher TIL fractions were more likely to have tumor-associated clones detectable in blood, suggesting these may be useful for tracking the immune response. These findings warrant validation in an independent cohort and exploration with other immunotherapeutics."

Biomarker • Clinical • Biosimilar • Melanoma

Translational evidence of reactivated innate and adaptive immunity with intratumoral IMO-2125 in combination with systemic checkpoint inhibitors from a Phase I/II study in patients with anti-PD-1 refractory metastatic melanoma (AACR 2017) - "These results demonstrate that IMO-2125 with a checkpoint inhibitor is a viable strategy to revive the immune response in tumors that are refractory to PD-1 inhibitors. Further clinical evaluation of both the IMO-ipilimumab and IMO-pembrolizumab combination is planned in a Phase 2 expansion of the current trial."

Biomarker • Checkpoint inhibition • Clinical • P1/2 data • Biosimilar • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology

Beware of squamous cell carcinoma Recurrent papillomatosis can go to the lungs [Google translation] (Medical Tribune) - "If the larynx is colonized with human papillomavirus types 6 and 11, one should always think about a potential infestation of the lungs. It can lead to recurrent respiratory papillomatosis - with a high risk of malignant degeneration....The lungs are also affected in up to 8.9 percent of patients. They have an increased morbidity, their lifetime risk of malignant degeneration is 32 times higher than with 'normal' RRP, write Dr. Sara Pai and colleagues...However, the possibility of pulmonary involvement is often not considered. Many lesions are more or less incidental because they do not cause symptoms in the early stages."

Media quote

Association of on-treatment plasma HGF levels with overall survival (OS) in patients (pts) with advanced renal cell carcinoma (RCC) treated with interferon alpha (INF) +/- bevacizumab (BEV): Results from CALGB 90206 (Alliance). (ASCO 2017) - P3; "In RCC pts with low baseline HGF levels (< median), levels remain consistently low and are associated with improved OS. Conversely, in pts with high baseline HGF levels results are split; some patients continue to have high levels on treatment and are associated with a worse OS, suggesting that, HGF predicts for therapeutic benefit and represents a potential mechanism of resistance."

Clinical • Biosimilar • Renal Cell Carcinoma

Clonality of T-cell repertoire in the tumor microenvironment (TME) and peripheral blood of metastatic melanoma patients treated with CTLA4 blockade and interferon-α (IFN). (ASCO-SITC 2017) - P2; "... Patients received tremelimumab 15 mg/kg I.V. every 12 weeks... T-cell clonality in the TME pretreatment is a promising biomarker of immunotherapeutic benefit in our study. While baseline PBMC clonality was not associated with clinical benefit, early on-treatment (day 29) was significantly associated. These findings require validation in an independent cohort and exploration in relation to other immunotherapeutics."

Biomarker • Clinical • Tumor microenvironment • Biosimilar • Melanoma • Oncology

A randomized phase II study of ipilimumab at 3 (ipi3) or 10 mg/kg (ipi10) alone or in combination with high dose interferon-alfa (HDI) in advanced melanoma (E3611). (ASCO 2017) - P2; "Prior data from a phase II of tremelimumab and HDI showed promising efficacy supporting the current study. Within the limitations of the sample size, there were no significant differences in PFS with HDI vs. no HDI or ipi10 vs. ipi3."

Clinical • Combination therapy • P2 data • Biosimilar • Cardiovascular • Immunology • Melanoma • Ophthalmology

A phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk melanoma (U.S. Intergroup E1609): Preliminary safety and efficacy of the ipilimumab arms. (ASCO 2017) - P3; "Adjuvant therapy of pts with high-risk melanoma is associated with significantly more toxicity at ipi10 compared to ipi3. An unplanned RFS analysis of concurrently randomized pts on the 2 ipi arms showed no difference in RFS."

Clinical • Head-to-Head • P3 data • Biosimilar • Melanoma

Phase 1b/2, open label, multicenter, study of intratumoral SD-101 in combination with pembrolizumab in anti-PD1 naïve & experienced metastatic melanoma patients. (ASCO 2017) - P1b/2; "...Background: SD-101 is a synthetic CpG-ODN agonist of TLR 9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells to activate T cell anti-tumor responses... The combination of SD-101 and pembro was well tolerated and demonstrates no worsening of the expected toxicities of each of the individual monotherapies. These interim data support enhanced activity of adding SD-101 to pembro in anti-PD-1 naive metastatic melanoma as well as potential activity in anti-PD-1 experienced pts. Additional follow up data through May 15, 2017 will be presented."

Clinical • Combination therapy • Biosimilar • Immunology • Melanoma • Pain

Intravesical rad-IFNα/Syn3 for patients with high-grade, bacillus Calmette-Guérin (BCG) refractory or relapsed non-muscle invasive bladder cancer: A phase II randomized study. (ASCO-GU 2017) - P2; "rAd-IFNα/Syn3 was well tolerated and demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who are unable or unwilling to undergo radical cystectomy. A phase III trial utilizing this novel agent is ongoing."

Clinical • P2 data • Bladder Cancer • Prostate Cancer

Sunitinib in patients with metastatic renal cell carcinoma: Clinical outcome according to IMDC risk group. (ASCO 2017) - P3; "This retrospective analysis provides ORR, PFS, and OS benchmarks for current and future clinical trial interpretation in mRCC pts with different prognostic risk treated with sunitinib."

Retrospective data • Biosimilar • Renal Cell Carcinoma

Prevention of Chemotherapy-Induced Nephrotoxicity in Children with Cancer. (PubMed, Int J Prev Med) - "...The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX)...CPL, mitomycin C, and gemcitabine treatment cause vascular injury and HUS. High-dose IFO, streptozocin, and azacitidine cause renal tubular dysfunction manifested by Fanconi syndrome, rickets, and osteomalacia. AKI is a common adverse effect of MTX, interferon-alpha, and nitrosourea compound treatment. These strategies to reduce the cytotoxic drug-induced nephrotoxicity should include adequate hydration, forced diuresis, and urinary alkalization. Amifostine, sodium thiosulfate, and diethyldithiocarbamate provide protection against CPL-induced renal toxicity."

Journal • Review • Biosimilar • Oncology • Renal Disease

Treatment of eosinophilic cellulitis (Wells syndrome) - a systematic review. (PubMed) - J Eur Acad Dermatol Venereol - "Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions."

Journal • Review • Biosimilar • Immunology

"Octreotide Plus Interferon Alfa-2b Versus Octreotide Plus Bevacizumab for Advanced Carcinoid Tumors https://t.co/AW1oSQRaV3 @JCO_ASCO" - pracuponc

Head-to-Head • Biosimilar

In vitro immunomodulatory properties of gemcitabine alone and in combination with interferon-alpha. (PubMed) - "Gemcitabine in combination with interferon-alpha demonstrated some immunomodulatory features, but these effects were interferon-alpha dependent. We concluded that combination of both drugs induces rather cumulative effects, supposing that these therapeutic could be applied together for a chemo-immunotherapy."

Journal • Biosimilar • Oncology • Pancreatic Cancer

Heat Shock Protein 47 Promotes Glioma Angiogenesis. (PubMed) - "Furthermore, HSP47 promoted glioma angiogenesis through HIF1α-VEGFR2 signaling. The present study demonstrates that HSP47 promotes glioma angiogenesis and highlights the importance of HSP47 as an attractive therapeutic target of GBM."

Journal • Biosimilar • Immunology • Oncology

Metformin inhibits vistatin gene expression via HIF1 in PC3 prostate cancer cells: a potential role for visfatin as a non-invasive biomarker (EASD 2017) - "Our data in PC3 cultured cells indicate that the anti-proliferative activity of metformin could be mediated, at least in part, through the HIF1/visfatin axis. Our findings also suggest that visfatin could serve as a non-invasive biomarker of aggressiveness in patients with PC."

Diabetes

REAL-LIFE DISCONTINUATION OF TKIS (SOHO 2016) - "METHODS: We reviewed charts of 18 CML patients among 60 treated at our institution between March 1989 and April 2016, who discontinued TKIs [imatinib (n=7), nilotinib (n=8), dasatinib (n=2) or ponatinib (n=1)] as first line (N=7) or salvage therapy (N=11) from September 2008 to April 2016.One patient, still in MR5, received IFN alfa for further 47 months after stopping imatinib. As expected, in our cohort, low SR at diagnosis, prior IFN and median cumulative TKI exposure before discontinuation were associated with longer relapse-free interval. Not the same for median duration of stable deep MR, probably suggesting the relevance of mechanisms additional to BCR-ABL inhibition in disease control."

Clinical • Acute Coronary Syndrome • Biosimilar • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Oncology

CHRONIC MYELOID LEUKEMIA PATIENTS WERE NOT DIFFERENT IN MOLECULAR RELAPSE AFTER STOPPING IMATINIB IN MR4 WHETHER RESIDUAL DISEASE WAS DETECTED OR NOT - WHEN ADJUSTING FOR NUMBER OF CONTROL TRANSCRIPTS (EHA 2017) - "Apart from type (ABL1 or GUSB) and number of control gene transcripts, matching variables were interferon alpha pre-treatment, duration of MR4, and the IM treatment time before observation of MR4. Using the MR4 threshold, after matching on number of control transcripts and other factors, results suggest little or no impact of detectability of BCR-ABL1 on RFS. Time in deep response seems to be more important. In daily routine, many labs produce reliable outcome at the MR4 but not always at the MR4.5 level."

Clinical • Biosimilar • Chronic Myeloid Leukemia

Iron accumulation in clear cell renal cell renal cell carcinoma and effects of iron deprivation on HIF2-α expression and cell survival (AACR 2017) - "...Micromolar concentrations of 3 clinical iron chelator drugs, deferoxamine (DFO), deferiprone (DFP), and deferisirox (DFX), were tested by MTT assay for effects on ccRCC versus benign renal cell proliferation... These data indicate that increases in intracellular iron content occur during human ccRCC tumorigenesis and support further investigation of iron chelation as a novel therapeutic strategy for targeting HIF2-α and inducing cancer cell death in ccRCC patients."

Biosimilar • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma

Type I IFN Blockade Restores Normal Transitional B Cell Development Post-Anti-CD20 Depletion (ACR-ARHP 2017) - "Type I interferons exert a prominent effect on the development of autoreactive B cells during a critical “window of opportunity” where transitional B cells are repopulating the periphery following B cell depletion therapy. Importantly, transient blockade of type I IFN during B cell repopulation was sufficient to prevent development of autoreactive B cells and antibodies long-term. These results suggest that blockade of type I IFN may be an effective therapeutic option to enhance and prolong the effects of B cell depletion therapy in lupus."

Lupus • Rheumatoid Arthritis

Interferon Alpha as Marker of Disease Severity in Children with Influenza: A Cohort Study (ATS 2017) - "Lower levels of interferon-α in children with more severe influenza infection reinforce experimental evidence about its protective role in influenza infection in humans. Moreover, it has a potential use as prognostic tests and give insight to treatment strategies"

Biomarker • Clinical • Biosimilar • Immunology

Reasons to be cheerful: One, two, three? (BSR 2017) - "Three different monoclonal antibodies (Rontalizumab, Silfalimumab and Anifrolumab) have been used in major clinical trials in SLE. For example, the importance of an increased interferon-alpha signature in the development of SLE is widely recognised. However other ongoing phase II trials utilising a novel recombinant FcɣIIB receptor [SM101] and RNP peptide (Lupuzor previously known as PI140) are now underway after encouraging animal-model and/or phase I studies. Benlysta which blocks the B-cell activating factor BAFF remains the only biologic to be formally approved in the UK and the USA for the treatment of lupus albeit under significant restrictions. Frustratingly, other approaches, for example, the use of Abatacept which blocks the antigen-presenting cell-T-cell interaction have not met their endpoints in clinical trials. In retrospect the significantly heterogeneous nature of lupus was always likely to make it more challenging to respond to individual biologic approaches. ...

Biosimilar • Immunology • Lupus • Psoriasis • Rheumatoid Arthritis

Pharmacodynamic changes confirm the mechanism of action mediating SD-101 efficacy, in combination with pembrolizumab, in a phase 1b/2 study in metastatic melanoma (MEL-01) (AACR 2017) - "...SD-101 stimulates dendritic cells to release interferon-alpha and mature into antigen presenting cells that effectively activate T cell responses... Biomarker assessments of the tumor microenvironment in melanoma patients receiving SD-101 and pembrolizumab demonstrate an immunophenotype with CD8 infiltration and a Th1 driven immune response consistent with the mechanism of action and anti-tumor activity of this combination."

Late-breaking abstract • Biosimilar • Melanoma • Oncology