On October 26, 2020 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported updated clinical results from the combination arm of the Company’s ongoing Phase 1/2 study evaluating ADXS-503 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy in non-small cell lung cancer (NSCLC) (Press release, Advaxis, OCT 26, 2020, View Source [SID1234569044]). ADXS-503 is the first drug construct from the Company’s ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program which leverages Advaxis’ proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary, tumor-associated antigens.

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Key data updates for the first 6 evaluable patients who have received ADXS-503 as an add-on therapy immediately following progression with KEYTRUDA, include:

Disease control rate of 67% (4/6 patients) and overall response rate of 17% (1/6 patients) achieved after immediate prior progression on KEYTRUDA with previous best responses of stable disease
Sustained clinical benefit with the first two treated patients remaining on treatment for over 43 and 33 weeks
Updated and new patient level data for the four patients with observed disease control, all of whom remain on study, include:
° Previously reported partial response (PR) with 60% tumor reduction seen on 8-week scan and sustained at 33-week scan in an elderly patient with non-squamous NSCLC who had received Pembrolizumab for approximately 30 months with a best overall response (BOR) of stable disease
° Previously reported stable disease (SD) with a 25% reduction in target lesion sustained at 43-week scan in an elderly patient with non-squamous NSCLC who had received Pembrolizumab for ~32 months with a BOR of stable disease.
° Stable disease (SD) confirmed on 13 week-scan in a patient with squamous NSCLC who had received Pembrolizumab for approximately 15 months with a BOR of stable disease
° Stable disease (SD) on 6 week-scan in a patient with non-squamous NSCLC who had received Pembrolizumab for approximately 14 months, including combination therapy with chemotherapy in the beginning
"I am highly encouraged by these data which suggest that treatment with ADXS-503 has the potential to re-sensitize or enhance response to KEYTRUDA, even in patients with immediate prior progression on treatment," said Dr. Andres Gutierrez, Chief Medical Officer of Advaxis. "Other checkpoint inhibitor rechallenge studies have reported disease control rates of approximately 45 percent, with these studies typically including bridging therapy, a change in checkpoint inhibitor, or an interruption in treatment of varying intervals. The 67% disease control rate demonstrated thus far in this ongoing study represents an impressive 50 percent improvement versus the disease control rate observed in other studies in similar settings. This improvement in the setting of uninterrupted treatment on KEYTRUDA is promising and suggests that ADXS-503 may be capable of re-stimulating the immune system to drive clinically meaningful benefit. The sustained durability of responses is also noteworthy, and I look forward to the continued evaluation of ADXS-503 in additional patients as we advance through the efficacy expansion phase of the study."

Ken Berlin, Chief Executive Officer of Advaxis, said, "We are pleased that the growing and maturing data from our ongoing ADXS-503 clinical trial suggest that this drug candidate may represent an important new treatment option for patients who have progressed on checkpoint inhibitors. Notably, all patients with disease control were on treatment with KEYTRUDA for over one year at the time of progression, with prior best responses that were limited to stable disease throughout their treatment. In addition, one patient with squamous histology also achieved stable disease, suggesting this regimen may be broadly applicable across NSCLC. As to the durability of tumor control, the first 2 evaluable patients remain on treatment with sustained clinical benefit for over 10 months, suggesting treatment with ADXS-503 is capable of providing long-term resensitization or enhancement to checkpoint inhibitors after disease progression."

Mr. Berlin continued, "Our belief is that ADXS-503, as an off-the-shelf neoantigen therapy that to date has a favorable safety and tolerability profile, may be broadly beneficial to lung cancer patients in diverse treatments settings and specifically, those with limited treatment options. These results, paired with our recent biomarker data that show on-mechanism activation of an immune response to ADXS-503 antigens, leave us increasingly confident that ADXS-503 has the potential to restore or enhance sensitivity to checkpoint inhibitors. We look forward to continued progress in our expanded clinical program, now evaluating patients in Part B, the efficacy expansion arm, and Part C, our expansion to the first line setting, both of which are continuing to enroll patients."

The Phase 1/2 clinical trial of ADXS-503 is seeking to establish the recommended dose, safety, tolerability and clinical activity of ADXS-503 administered alone and in combination with a KEYTRUDA in approximately 50 patients with NSCLC, in at least five sites across the U.S. The two dose levels with monotherapy in Part A, (1 X108 and 5 X108 CFU) have been completed. Part B with ADXS-503 (1 X108 CFU) in combination with KEYTRUDA is currently enrolling its efficacy expansion for up to 15 patients at dose level 1 (1 X108 CFU + KEYTRUDA) with the potential to proceed to dose level 2 (5 X108 CFU + KEYTRUDA) at a later date. Part C, which is evaluating ADXS-503 in combination with KEYTRUDA (1 X108 CFU + KEYTRUDA) as a first line treatment for patients with NSCLC with PD-L1 expression ≥ 1% or who are unfit for chemotherapy is currently enrolling patients.

About ADXS-HOT
ADXS-HOT is a program that leverages the Company’s proprietary Lm technology to target hotspot mutations that commonly occur in specific cancer types. ADXS-HOT drug candidates are designed to target acquired shared or "public" mutations in tumor driver genes along with other proprietary cancer-testes and oncofetal tumor-associated antigens that also commonly occur in specific cancer types. ADXS-HOT drug candidates are an off-the-shelf treatment, designed to potentially treat all patients with a specific cancer type, without the need for pretreatment biomarker testing, DNA sequencing or diagnostic testing.

On October 26, 2020 Anpac Bio-Medical Science Co., Ltd. ("Anpac Bio," the "Company" or "we") (ANPC), a biotechnology company with operations in China and the United States focused on early cancer screening and detection, reported that it has completed over 200,000 cancer detection tests as of September 30, 2020 using its biophysics based cancer screening technology, Cancer Differentiation Analysis ("CDA") (Press release, Anpac Bio, OCT 26, 2020, View Source [SID1234569063]).The CDA technology allows cancer screening for close to 60 types of cancer, including certain cancer types such as esophageal cancer and brain tumors which do not yet have other more-established blood based testing methods.

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As of June 30, 2020, the Company completed an accumulated number of CDA-based tests to 180,673. Since then, Company has carried out over 20,000 additional tests by the end of September, bringing the total number of tests over 200,000.

Dr. Chris Yu, CEO and Chairman of Anpac Bio commented, "We are very pleased to have achieved this milestone of over 200,000 completed biophysics based CDA tests. The rapid increasing number of tests we have achieved indicates the viability and popularity of our products, and indicates that biophysics based cancer screening technology can be an effective alternative approach to traditional cancer screening methods due to its advantages in a number of critical areas, including the detection of multiple cancer types at earlier stages due to a high level of sensitivity and specificity and low cost approach."

On October 26, 2020 NBE-Therapeutics, a Swiss-based company developing best-in-class cancer therapies based on its proprietary, highly differentiated Antibody-Drug Conjugate (ADC) platform, reported that it has commenced first-in-human studies of its lead program NBE-002 targeting ROR1, for triple negative breast cancer (TNBC) and other solid tumors (Press release, NBE Therapeutics, OCT 26, 2020, View Source [SID1234569081]).

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This phase 1/2, open label study will evaluate the recommended dose for further clinical development, safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of NBE-002, a novel anti-ROR1 antibody-drug conjugate, in patients with advanced solid tumors. Initial results from the study are expected in 2021.

The clinical study (NCT04441099) is being led by globally renowned investigators in the fields of oncology and antibody-drug conjugates, including: Anthony W Tolcher, MD from NEXT Oncology, San Antonio, Texas; Funda Meric-Bernstam, MD from The University of Texas MD Anderson Cancer Center, Houston, Texas; and Meredith McKean, MD from Sarah Cannon Research Institute – TN Oncology, Nashville, Tennessee.

NBE-Therapeutics’ best-in-class iADC platform creates highly potent, safe and immune-stimulatory ADCs with a novel anthracycline payload, which have been shown to induce a long-lasting anti-tumor immunity in pre-clinical models of solid tumors. Lead candidate NBE-002 has shown a remarkable therapeutic index (a measure of extremely high safety and tolerability) during non-clinical development.

Bertrand Damour, CEO of NBE-Therapeutics, said: "The first patient was enrolled in July 2020 and we are already at the third dose level. l am very pleased that the trial is progressing so well. Our goal is to develop best-in-class oncology treatments to increase survival, with the potential to cure solid tumors and to improve quality of life for cancer patients worldwide. The start of this trial represents an important milestone for NBE-Therapeutics to clinically demonstrate that our ADC platform has a highly favorable safety profile alongside significant efficacy in multiple pipeline programs. We look forward to continued progress with our ADCs in advanced solid tumors."

Dr. Ulf Grawunder, Founder, COO & CDO of NBE-Therapeutics, said: "We consider NBE-002 the best-in-class ROR1 targeting ADC in development, and are excited it has entered the clinic. In pre-clinical, solid tumor studies NBE’s novel iADC platform has shown unparalleled safety and efficacy, together with induction of anti-tumor immune memory. This immune-oncology function also prevented tumor re-growth upon tumor re-challenge, after complete regression had been achieved in preclinical tumor models. If this dual function translates into clinical benefit, NBE’s iADC platform could transform cancer medicine."

To read more: Clinicaltrials.gov NCT number: NCT04441099

About ROR1

ROR1 is receptor tyrosine kinase-like orphan receptor 1. It is a cell-surface protein that is expressed during embryofetal development but disappears before birth and is usually not expressed on normal cells in children or adults. ROR1 can, however, reappear on malignant tissues and may be expressed across a broad variety of cancer types including solid tumors. By addressing ROR1 cancer-fighting therapeutics can be selectively targeted to tumor cells, while sparing normal cells.

On October 26, 2020 Rain Therapeutics Inc., a privately-held, clinical stage biotechnology company focused on targeted therapies for patients with cancer, reported an update on data from the Phase 1 clinical trial of RAIN-32 (milademetan), an oral MDM2 inhibitor, during a late-breaker oral presentation at the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Virtual Symposium on October 25, 2020 (Press release, Rain Therapeutics, OCT 26, 2020, View Source [SID1234569045]).

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The presentation highlighted the enhanced safety profile of RAIN-32, enabled by its unique drug-like properties, when administered on an intermittent dosing schedule as well as prolonged progression-free survival in patients with well-differentiated/de-differentiated (WD/DD) liposarcoma (LPS).

"We are pleased to highlight these positive data," said Avanish Vellanki, co-founder and chief executive officer of Rain. "These analyses of the Phase 1 study demonstrate the opportunity for RAIN-32 to provide safe and effective MDM2 inhibition. We look forward to further evaluating RAIN-32 both in liposarcoma, as well as in other solid tumor indications characterized by MDM2 gene amplification with this dosing regimen."

The Phase 1 dose escalation and expansion study evaluated RAIN-32 across four dose schedules in patients (n=107) with liposarcoma, solid tumors or lymphomas. Key findings from the oral presentation include:

An intermittent dose schedule of QD 3/14 x 2 of a 28-day cycle (Schedule D) allowed the highest MTD for RAIN-32 (260 mg) versus the more continuous dose schedules (Schedules A, B and C)
RAIN-32 dosed on Schedule D at 260 mg exhibited an improved safety profile versus the more continuous dosing schedules:
Incidence of all ≥ Gr 3 TEAEs in the 260 mg Schedule D cohort (n=20) fell to 20% versus 55% in the Schedules A, B, and C cohorts (n=78)
Incidence of ≥ Gr 3 thrombocytopenia, neutropenia and anemia, representing the predominant dose-limiting toxicities of MDM2 inhibition, fell to 15%, 5% and 0% in Schedule D from 35%, 18% and 10% in the other schedules, respectively
No Gr 4/5 toxicities were observed at 260 mg dose in Schedule D
The Schedule D regimen also conferred numerically improved progression-free survival as compared to the continuous dose schedules
In 17 patients evaluable for efficacy receiving Schedule D at doses ≤ 260 mg, median progression-free survival was 8.0 months
The 260 mg Schedule D regimen has been identified as the dose and schedule for further studies
Tumor shrinkage and objective responses were also observed in selected non-liposarcoma patients with MDM2 gene amplification, indicating potential for future agnostic clinical trials using biomarker selection
Rain intends to initiate subsequent clinical studies of RAIN-32 in liposarcoma and other tumors in the second half of 2021.

About RAIN-32
RAIN-32 has been evaluated in patients with various solid tumors, acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and has received Orphan Drug Designation for the treatment of liposarcoma. RAIN-32 also has been evaluated in continuous and intermittent dose schedules that may offer a differentiated tolerability profile as compared to other MDM2 programs.

A separate clinical study for RAIN-32 is ongoing to evaluate safety and efficacy in patients with FLT3-ITD AML in combination with the FLT3 inhibitor, quizartinib. In addition, multiple investigator-sponsored studies are being conducted by MD Anderson Cancer Center (MDACC) as well as National Cancer Center Hospital (NCCH) in Tokyo, Japan.

On October 26, 2020 NANOBIOTIX (Euronext : NANO – ISIN : FR0011341205 – the ‘‘Company’’) reported updates to the Company’s global development plan for first-in-class radioenhancer NBTXR3 at the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting (Press release, Nanobiotix, OCT 26, 2020, View Source [SID1234569064]).

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While the COVID-19 crisis and subsequent measures to curtail the spread of the virus have created challenges in clinical trial recruitment, a sharpened focus on the Company’s priority pathways in head and neck cancer and immunotherapy has led to the continued achievement of necessary milestones for the development of lead product candidate NBTXR3. Moreover, diligent efforts in collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) in the United States (US) has helped to advance expansion of the development plan across new indications.

Priority Development in Head and Neck Cancer and Immunotherapy

Pathway to Global Registration in Head and Neck Cancer On Track

Nanobiotix has presented an update on the expansion part of the Company’s phase I study evaluating NBTXR3 activated by radiation therapy for patients with head and neck cancer (Study 102) at ASTRO 2020. In 31 evaluable patients, positive results confirmed the target lesion objective response rate presented earlier this year at 83.9% and showed an increase in target lesion complete response rate at 67.7%. The target lesion complete response rate is an increase over previously reported data (60%) with additional follow up (7.8-month median follow up vs. 5 months). Additionally, data showed an overall objective response rate of 83.9% and an overall complete response rate of 48.4%, which were also increases over previously reported data (83% and 43% respectively).

The trial has recruited 44 patients in total (31 evaluable to date), and will remain ongoing until reaching 44 evaluable patients. The next update on the study is expected in the second quarter of 2021.

Preparation for the Company’s pivotal phase III trial evaluating NBTXR3 activated by radiation therapy for patients with head and neck cancer (NANORAY-312) is ongoing as planned. The trial is expected to commence after the financing to fund the trial is secured.

As previously announced, NBTXR3 activated by radiation therapy for the population in NANORAY-312 received Fast Track designation from the US Food and Drug Administration (FDA) in February 2020. Fast Track is a process designed to facilitate the development and accelerate the review of drugs for serious conditions and that have the potential to address unmet medical needs. The purpose is to expedite the availability of new treatment options for patients.

First Clinical Data in Immunotherapy to be Presented in Coming Weeks

Nanobiotix will present the first clinical results from a phase I study evaluating NBTXR3 activated by radiation therapy in combination with pembrolizumab or nivolumab for patients with head and neck cancer, lung metastasis and/or liver metastasis (Study 1100) by the end of 2020.

Nine patients have been injected in the trial thus far and recruitment remains ongoing. After the release of first results, the next step for the trial will be establishment of the recommended phase II dose (RP2D) by mid year 2021 for the head and neck cancer cohort and the lung metastasis cohort, and in the second half of 2021 for the liver metastasis cohort.

Early-Stage Development Across Other Solid Tumor Indications and with Collaborators

Nanobiotix Trials in Additional Solid Tumor Indications

The dose escalation part of the Company’s phase I/II trial evaluating NBTXR3 activated by radiation therapy for the treatment of patients with hepatocellular carcinoma (HCC) or liver metastasis (Study 103) has completed successfully and final data has been presented at ASTRO 2020. Data showed that the product candidate continues to be safe and well tolerated with no dose-limiting toxicities (DLTs). Early efficacy data showed a target lesion objective response rate of 90.9% in evaluable patients with hepatocellular carcinoma (HCC) and a target lesion objective response rate of 71.4% in evaluable patients with liver metastasis. Further development in this indication will proceed after the launch of the Company’s phase III head and neck cancer trial.

The Company’s phase I trial evaluating NBTXR3 activated by radiation therapy for the treatment of patients with prostate cancer (Study 104) has administered NBTXR3 to five patients, with no serious adverse events and no DLTs reported. At present the Company has paused development in this indication to focus resources on the head and neck cancer and immunotherapy pathways.

In soft tissue sarcoma, the final patient follow up visit has been completed in the phase III Act.In.Sarc study. The planned post-registrational trial is expected to launch in 2021.

Trials with Collaborators

The Company’s clinical collaboration with MD Anderson continues to move forward with the launch of a phase I trial evaluating NBTXR3 activated by radiation therapy for patients with pancreatic cancer. FDA ‘Safe to Proceed’ notifications have been received for four additional trials in the collaboration and are pending activation.

About NBTXR3

NBTXR3 is a first-in-class radioenhancer composed of functionalized hafnium oxide nanoparticles that is administered via one-time intra-tumoral injection and activated by radiation therapy. The physical and universal mode of action (MoA) of NBTXR3 is designed to trigger cellular destruction death and adaptive immune response.

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. In February 2020, the United States Food and Drug Administration granted the regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced head and neck squamous cell cancer who are not eligible for platinum-based chemotherapy.

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 is also engaged in a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to further expand the NBTXR3 development program.