Many of VHIO´s leading clinical investigators are currently participating at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, 02 -06 June. From among some 5,700 abstracts submitted to first outing during the world´s most prestigious meeting in clinical oncology convening some 38, 000 oncologists from across the globe, several from VHIO were selected by ASCO and are currently being presented on the ground in Chicago.
In addition to the many VHIO studies that were accepted by ASCO to showcase as oral or poster presentations during this year´s meeting, VHIO faculty have also been selected to chair and speak at various sessions. VHIO´s Director, Josep Tabernero, for example, will co-chair a joint ASCO – European Society of Medical Oncology (ESMO) Special Session entitled Access to Clinical Care in Cancer Medicines, Saturday 03 June, 13:15 – 14:30 (Room S102).
In his capacity as President-elect of ESMO and Chair of its Cancer Medicines Working Group, Josep will chair this Session alongside Daniel F. Hayes from the Michigan Comprehensive Cancer Center. A panel of internationally renowned experts will update on ASCO´s Value Framework, ESMO´s Magnitude of Clinical Benefit Scale, the improved application of treatment pathways towards better outcomes, and there will also be a talk centering on value-based access to cancer medicines from the Catalonian perspective – to be presented by Ana Clopes from the Catalan Institute of Oncology (ICO).
A hand-pick of just some of the many VHIO studies showcasing at ASCO:
Novel bispecific agent as mono or in combo with paired immunotherapy promises increased therapeutic efficacy against metastatic colorectal cancer
Josep Tabernero, also Head of the Medical Oncology Department of the Vall d´Hebron University Hospital (HUVH), will present, as first author, promising results from phase Ia and phase Ib studies on the preliminary therapeutic activity and safety of the novel carcinoembryonic antigen (CEA) T-cell bispecific (CEA CD3 TCB ) antibody, either as monotherapy or in combination with PD-L1 inhibitor atezolizumab, during an Oral Abstract Session on Developmental Therapeutics – Immunotherapy, Monday 05 June, 13:39h (Chicago local time), Hall D1.
More to come about these two studies, also co-authored by Guillem Argilés, Medical Oncologist at the Vall d´Hebron University Hospital (HUVH) and Clinical Investigator of VHIO´s Gastrointestinal and Endocrine Tumors Group led by Josep Tabernero, here on VHIO´s website directly following his presentation on Monday.
Findings from a phase I clinical study exploring the efficacy of combining ALK inhibitor Ceritinib with immunotherapy against lung cancer
Enriqueta Felip, Principal Investigator of VHIO´s Thoracic Tumours & Head and Neck Cancer Group, will also be delivering an oral presentation at this year´s Annual ASCO meeting. On Saturday 03 June, at 13:39h (Chicago local time) during a Session dedicated to Developmental Therapeutics — Clinical Pharmacology and Experimental Therapeutics, Enriqueta will reveal the results of a phase I multi-center international trial designed to assess the safety and dose escalation of the combination ceritinib plus nivolumab (NIVO) in patients with advanced ALK+ non–small-cell lung cancer (NSCLC).
“For the first time, this early phase trial was conducted to assess whether the combination of ceritinib — a targeted therapy against ALK — plus a PD1 inhibitor (NIVO) provides sustained clinical benefit in patients with NSCLC with ALK+”, highlights Enriqueta.
The phase I dose escalation study enrolled patients with advanced ALK+ non–small-cell lung cancer (NSCLC) in stage IIIB/IV. These patients were divided into two groups: those previously treated with ALK inhibitors or chemotherapy, and those who had not received prior therapy. “The combination of the two drugs was evaluated in two cohorts with two different doses. While our results showed that the ceritinib-NIVO duo is active in patients with NSCLC ALK+, a high degree of toxicity, especially skin toxicity, was observed. The protocol on the administration of this combination of drugs will consequently be amended to address these toxicities”, she concludes.
The promise of PARP inhibitors for patients with metastatic breast cancer and BRCA1/BRCA2 mutations
Judith Balmaña, Principal Investigator of the VHIO´s High Risk and Cancer Prevention Group, is co-author of a phase II study assessing the efficacy talazoparib, a PARP inhibitor, in patients with metastatic breast cancer and BRCA1/BRCA2 mutations. The final results of this clinical trial will showcase as an oral presentation during session on metastatic breast cancer on Saturday, 3 June, at 15:27h (Chicago local time) in Hall D1.
The BRCA1 and BRCA2 genes encode two key DNA damage response proteins. When faulty, genetic instability occurs and women are at higher risk of developing breast or ovarian cancer at an earlier age, due to a deficiency in DNA damage repair. Up to 5% of women with breast cancer can have BRCA1 or BRCA2 germline mutations. Patients diagnosed at an early age, with triple negative breast cancer or with a family history may have up to a 25% likelihood of having a BRCA germline mutation (inherited).
The study included two groups: the first consisted of patients who had received treatment with carboplatin or cisplatin and who did not progress immediately but at least 8 weeks later; these patients were exposed to this drug but did not progress while being treated with it. The second group included patients who had received 3 or more lines of chemotherapy and were considered multi-treated within the metastatic setting, and may have acquired different mechanisms of resistance to targeted therapies. Administering this PARP inhibitor to these patients yielded very encouraging results.
PARP inhibitors effectively kill tumour cells with BRCA1 or BRCA2 mutations. “The majority of tumors that occur in these patients have one inherited mutated BRCA gene and during tumorigenesis they lose the wild-type gene (non-mutated). Therefore, these tumors do not have the corresponding BRCA protein and are lacking one of the main mechanisms of DNA repair; the homologous recombination repair system. The non-cancer cells from these patients have the ability to repair DNA damage because they only have the inherited mutated BRCA gene. This difference between cancer and non-cancer cells has been critical in developing specific targeted therapies that kill cancer cells and cause little toxicity in the non-cancer cells”, explains Judith Balmaña.
PARP inhibitors represent the first targeted therapy for patients with breast cancer and a germline BRCA mutation and are now being evaluated in the adjuvant and neoadjuvant setting and also in combination with other drugs involved in DNA damage response.
The results from this Phase II trial are very promising and indicate that 1 out of every 4 or 5 patients who have previously received cisplatin – a population notoriously associated with resistance to therapy, respond well to treatment with talazoparib, with manageable side effects. The response rate in the other group of multi-treated patients was near-on 40%.
“For the first time, an inherited genetic mutation that triggers predisposition to developing breast cancer is translating into therapeutic opportunity. BRCA is a therapeutic target with immediate impact at clinical level for those patients who already have cancer. The identification of a germline mutation in BRCA1 or BRCA2 through genetic testing in blood samples now promises associated therapeutic benefit”, she observes.
The results of another study involving PARP inhibitors, a phase III trial of olaparib monotherapy versus chemotherapy for patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, will be presented during a Plenary Session on breast cancer, Sunday 04 June, 15:10h (local time in Chicago) in Hall B1. This phase III trial, led by Mark Robson, Memorial Sloan Kettering Cancer Center (MSKCC) in New York, was mainly conducted in the US, with independent sites ROW. While VHIO did not participate in the phase III, it played a critical role in the early drug development stages of this novel agent, including a phase II study, and a phase I in combination with cisplatin.
VHIO is currently leading pioneering researching into the mechanisms of resistance to PARP inhibitors through a project that combines the expertise of its High Risk and Cancer Prevention Group, led by Dr Balmaña, Breast Cancer and Melanoma Group, headed by Cristina Saura, and Experimental Therapeutics Group, directed by Violeta Serra. Aimed at driving novel and more effective anti-cancer therapies, VHIO is also assessing drug-drug combinations tested preclinically in PDX models based on identified mechanisms of resistance, exploring clinical biomarkers of sensitivity to PARP inhibitors towards better defining which patients may benefit most, and unmasking the underlying mechanisms of sensitivity to these anti-cancer novel therapies to extend their use beyond patients with a BRCA mutation.
In addition to these highlighted VHIO studies, several important findings submitted by leading clinical investigators at VHIO´s Research Unit for Molecular Therapy of Cancer (UITM) - "la Caixa", were also selected by ASCO as oral as well as poster presentations.
During a Poster Session on Head and Neck Cancer on Monday, 05 June, at 13:15 PM (local time in Chicago) in Hall A, results from the Impact of early trials in molecularly-characterized patients with head and neck cancer will be presented. The most common histological subtype of head and neck cancers is squamous cell carcinoma. Other localizations with different subtypes include nasopharyngeal, nasal-sinual, and salivary gland tumors. As evidenced in the literature, head and neck tumors present different molecular alterations.
Clinical investigators at VHIO and the Vall d´Hebron University Hospital (HUVH) led this study to assess head and neck cancer patients enrolled in clinical studies being treated with targeted therapies matched to their specific molecular alterations – as identified by VHIO´s Cancer Genomics Group´s suite of cutting-edge sequencing platforms, directed by Ana Vivancos.
This research, carried out from 2010 to 2016, evaluated 47 patients across 57 clinical trials with targeted therapies based on their established individual molecular make-up of disease, in order to measure clinical benefit of the respective novel treatments. Clinical benefit was measured according to time to progression, clinical benefit scale, and the quotient between progression free survival of the respective study drug with respect to standard therapy previously received.
The median time to progression was 9.3 months without differences across the various tumor types and no differences reported in relation to clinical benefit based on targeted treatments and histological types. On the other hand, despite being a very pre-selected population based on individual molecular profiles and previously administered therapies, a clinical gain was observed in patients with salivary gland and nasopharynx tumors treated with whichever of the selected targeted therapies, as well as a greater clinical benefit in patients with head and neck squamous carcinoma treated with immunotherapy.
Crucial to this study has been the pioneering research led by Rodrigo Dienstmann, Principal Investigator of VHIO´s Oncology Data Science (ODysSey) Group, that has succeeded in better and more precisely sub-typing disease in order to better guide treatment decisions and strategies based on the molecular specificities of each individual patient´s cancer.
Neus Basté, Medical Oncologist at the Vall d´Hebron University Hospital (HUVH), and Clinical Investigator of VHIO´s Thoracic Tumors & Head and Neck Cancer Group directed by Enriqueta Felip, is first author of this study and will present these results as a poster during the penultimate day of ASCO´s 2017 Annual Meeting.