On May 29, 2020 NANOBIOTIX (Paris:NANO)(Euronext: NANO – ISIN: FR0011341205 – the "Company"), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported new data from the expansion part of its phase I trial, evaluating the potential of first-in-class NBTXR3 activated by radiation therapy to improve treatment outcomes for elderly patients with locally advanced head and neck cancer ineligible for chemotherapy or intolerant to cetuximab (Press release, Nanobiotix, MAY 29, 2020, View Source [SID1234558735]). The data were published as part of the virtual scientific program at the 2020 annual meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper).

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Study 102: A phase I trial of hafnium oxide nanoparticles activated by radiotherapy in cisplatin-ineligible locally advanced HNSCC patients

Authors: Christophe Le Tourneau, Valentin Calugaru, Edith Borcoman, Victor Moreno, Emiliano Calvo, Xavier Liem, Sebastien Salas, Bernard Doger, Olivier Choussy, Maria Lesnik, Xavier Mirabel, Nathalie Badois, Samar Krhili, Josefin Blomkvist, Nicolas Fakhry, Stéphanie Wong-Hee-Kam, Caroline Hoffmann.

J Clin Oncol 38: 2020 (suppl; abstr 6573). DOI: 10.1200/JCO.2020.38.15_suppl.6573.

Abstract Number: 6573

Study Design

After reporting promising early signs of activity from the dose escalation part of its phase I trial evaluating the safety and feasibility of NBTXR3 activated by radiation therapy in elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the Company launched an expansion cohort to confirm results and observed trends with a larger population treated at the recommended dose. This part of the study is expected to recruit a total of 44 evaluable patients. To date, 40 patients have been recruited, 30 of whom are evaluable for efficacy and are included in the data presented at ASCO (Free ASCO Whitepaper) 2020.

Topline Results

As previously announced, in the dose escalation part of the study NBTXR3 activated by radiation therapy was safe and well tolerated. The recommended phase 2 dose (RP2D) was determined to be 22% of baseline tumor volume. Among 16 evaluable patients, injected lesion complete response rate was 56% and overall objective response rate was 69%.

Regarding the new, expansion part data, analysis of 40 patients dosed showed that NBTXR3 activated by radiation therapy remains safe and well tolerated. In terms of efficacy, for the 30 evaluable patients, investigators observed, at a median time of 5 months after NBTXR3 injection, an overall objective response rate of 83% and an overall complete response rate of 43% and objective response rate of the primary tumor (target lesion) of 83% with a complete response rate of the primary tumor of 60%. The safety profile was consistent with the dose escalation part and the efficacy data improved (i.e. an increase in overall objective response rate from 69% in the dose escalation part to 83% in the dose expansion part).

In the safety population (all treated patients, N=40), three serious adverse events (SAEs) related to NBTXR3 were observed (0.7% of all AEs), comprising one case each of: Grade 4 tumor hemorrhage also related to radiotherapy, Grade 3 mucosal inflammation and Grade 2 swollen tongue also related to the injection procedure. Two SAEs related to the injection procedure were reported (0.5% of all AEs), comprising: two cases of swollen tongue, of which one was Grade 2 and also related to NBTXR3, and one was Grade 4. The radiotherapy-associated safety profile was as expected with the most frequently occurring AEs being stomatitis and skin injury. Three deaths due to AEs related to radiotherapy and other causes were observed. Four other patients died of non-oncologic or non-toxicity-related reasons.

Next Steps in Head and Neck Cancer

The expansion part of the phase I trial will continue to recruit until reaching 44 evaluable patients. In parallel, subject to the FDA’s pending review, the Company intends to globally launch a pivotal phase III trial. In the planned phase III trial, a futility analysis is expected 18 months after the first patient is randomized, and an interim analysis of progression-free survival (PFS) is expected at 24-30 months.

NBTXR3 for the treatment of locally advanced HNSCC patients who are not eligible for platinum-based chemotherapy received Fast Track designation from the FDA in February 2020. Fast Track designation is a process designed to facilitate the development and accelerate the review of drugs for serious conditions that have the potential to address unmet medical needs. The purpose is to expedite the availability of new treatment options for patients.

About NBTXR3

NBTXR3 is a first-in-class product designed to destroy tumors through physical cell death when activated by radiotherapy. NBTXR3 has a high degree of biocompatibility, requires one single administration before the first radiotherapy treatment session, and has the ability to fit into current worldwide radiation therapy standards of care. The physical mode of action of NBTXR3 makes it applicable across solid tumors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) of the oral cavity or oropharynx in elderly patients unable to receive chemotherapy or cetuximab with limited therapeutic options. Promising results have been observed in the phase I trial regarding local control. In the United States, the Company has started the regulatory process to commence a phase III clinical trial in locally advanced head and neck cancers.

Nanobiotix is also running an Immuno-Oncology development program. The Company has launched a Phase I clinical trial of NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors in locoregional recurrent (LRR) or recurrent and metastatic (R/M) HNSCC amenable to re-irradiation of the HN and lung or liver metastases (mets) from any primary cancer eligible for anti-PD-1 therapy.

Other ongoing NBTXR3 trials are treating patients with hepatocellular carcinoma (HCC) or liver metastases, locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and pancreatic cancer. The Company has a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center (initially expected to support 9 new clinical trials in the United States) to evaluate NBTXR3 across several cancer types.

On May 29, 2020 Personalis, Inc., (Nasdaq: PSNL) a leader in advanced genomics for cancer, reported that the company will present new data in abstracts to be presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Meeting, which will be held May 29-31, 2020 (Press release, Personalis, MAY 29, 2020, View Source [SID1234558734]).

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One abstract showcases data from the ImmunoID NeXT Platform, the first platform to enable comprehensive analysis of both a tumor and its immune microenvironment from a single sample. ImmunoID NeXT can be used to investigate the key tumor- and immune-related areas of cancer biology, consolidating multiple oncology biomarker assays into one and maximizing the biological information that can be generated from a precious tumor specimen.

Another abstract highlights data from the Personalis NeXT Dx Test, one of the first cancer diagnostic platforms to profile approximately 20,000 genes in both the tumor exome and transcriptome, providing a comprehensive genomic testing solution that goes beyond many existing cancer diagnostic panels that focus on a few hundred genes. The Personalis NeXT Dx Test includes advanced analytics to provide a diagnostic report on genetic alterations in clinically-important cancer genes, as well as emerging immunotherapy composite biomarkers of medical importance.

Following are details and links to the abstracts that will be presented at the online meeting.

Abstract Number &
Session Title

Title & Presenter

Date

Location

6557
Head and Neck Cancers

Exome scale liquid biopsy characterization of putative neoantigens and genomic biomarkers pre- and post anti-PD-1 therapy in squamous cell carcinoma of the head and neck.
Presenter: Charles Abbott

May 29, 2020

Online

e15583
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Validation of an exome and transcriptome based diagnostic platform enabling clinical cancer therapy selection and emerging composite biomarkers for immunotherapy.
Presenter: Sebastian Saldivar

On May 29, 2020 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that Chief Executive Officer Rachel King will provide a company overview at the upcoming Jefferies Virtual Healthcare Conference (Press release, GlycoMimetics, MAY 29, 2020, View Source [SID1234558733]). The presentation will be available on the company’s website at the "Investors" tab for 30 days, beginning Thursday, June 4 from 1:00 – 1:25 p.m. EDT.

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To access the live webcast and subsequent archived recordings for the presentation, please visit the GlycoMimetics website at View Source

On May 29, 2020 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported that it will present at the Jefferies Virtual Healthcare Conference on Wednesday, June 3, 2020, at 9:00 a.m. Eastern Time (Press release, Odonate Therapeutics, MAY 29, 2020, View Source [SID1234558732]).

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On May 29, 2020 Bayer reported that Updated clinical data for Vitrakvi (larotrectinib) show continued high response rates and duration of response with longer follow-up and consistent safety in an expanded data set of 116 adult patients with tropomyosin receptor kinase (TRK) fusion cancer, including those with brain metastases (Press release, Bayer, MAY 29, 2020, View Source [SID1234558731]). A separate descriptive analysis evaluated quality of life (QoL) measures for adult and pediatric patients, including infants younger than 2 years, using clinical questionnaires. These findings are being presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program, held from May 29-31, 2020.

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Vitrakvi is approved in the U.S., Canada, Brazil and the European Union (EU). In the U.S., Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that have progressed following treatment. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Additional filings in other regions are underway or planned.

"With more patients added and a longer follow-up, we continue to see efficacy and a consistent safety profile for larotrectinib, regardless of tumor types, in adult patients with solid tumors harboring a TRK fusion. In addition, new data provide an understanding of quality of life results for the majority of adults, children and infants with TRK fusion-positive cancers treated with larotrectinib," said Alexander Drilon, M.D. Acting Chief of Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York, USA. "These data underscore the importance of routine genomic testing for people diagnosed with cancer, so that we can identify and match appropriate patients with the right treatment approach."

Updated data with a cut-off of July 15, 2019 in 116 adult patients with TRK fusion cancer across 17 tumor types showed an overall response rate (ORR) per investigator assessment of 71 percent (95 percent CI 62–79) with 10 percent complete responses (CRs) and 60 percent partial responses (PRs) (2 percent pending confirmation). For patients with brain metastases (n=14), the ORR was 71 percent (95 percent CI 42–92) with 10 patients having partial responses. The median duration of response was 35.2 months (95 percent CI 21.6–not estimable [NE]) at a median follow-up of 17.4 months. The median progression-free survival was 25.8 months (95 percent CI 15.2–NE) at a median follow-up of 14.6 months. The rate of overall survival (OS) at ≥ 12 months was 87 percent.1 In the primary data set at the time of FDA approval, Vitrakvi demonstrated an ORR of 75 percent (n=55) (95 percent CI, 61-85) by independent review committee, including a 22 percent CR rate and 53 percent PR rate across various solid tumors harboring a TRK fusion in adults and children (n=55). The median duration of response was not yet reached (range 1.6+ to 33.2+) (n=44).

"These analyses add to the breadth of data including long-term follow-up with Vitrakvi, supporting its use as an efficacious treatment for adults and children with TRK fusion cancer," said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. "Our continued study of cancers caused by genomic alterations underscores our commitment to developing treatments like Vitrakvi for patients and the physicians who serve them."

The safety profile was consistent with that of the overall safety population previously reported. The majority of adverse events (AEs) reported were grade 1 or 2. One patient (1 percent) discontinued due to a larotrectinib-related AE. No treatment-related grade 3 or 4 AEs occurred in more than 3 percent of patients and no treatment-related deaths were reported.1

In an additional analysis, QoL data were collected from the larotrectinib trials using EORTC QLQ-C30 (adults) and PedsQL (children) questionnaires, and were analyzed descriptively and longitudinally. The proportion of patients above 2 years with normal or above and below normal QoL scores, compared to values in the literature for the U.S. general population, was also calculated. QoL scores for most patients ≥2 years were either maintained within or moved into the normal range during larotrectinib treatment.2

Data for both these analyses presented at ASCO (Free ASCO Whitepaper) were pooled from three larotrectinib clinical trials (NCT02122913, NCT02576431 and NCT02637687) in adult and pediatric patients with TRK fusion cancer.2

Dr. Alexander Drilon has provided compensated advisory services to Bayer.

About Vitrakvi (larotrectinib)3

Vitrakvi (larotrectinib) is indicated for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are either metastatic or where surgical resection will likely result in severe morbidity and have no satisfactory alternative treatments or that have progressed following treatment.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information for Vitrakvi (larotrectinib)

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurologic adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.

Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.

Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.

Please see the full Prescribing Information for VITRAKVI (larotrectinib).

About TRK Fusion Cancer

TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless to where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now expands to six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.