On May 19, 2021Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, reported that kit will report initial data from its Phase 2 SPEARHEAD-1 trial, with afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) congress (Press release, Adaptimmune, MAY 19, 2021, View Source [SID1234580334]). Full abstracts were released online today. Data will be presented in an oral presentation by Dr. Sandra D’Angelo of the Memorial Sloan Kettering Cancer Center (Abstract #11504) on June 4th.

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"Patients are seeing substantial benefit from afami-cel in SPEARHEAD-1 across a broad range of cell doses and levels of MAGE-A4 expression," said Adrian Rawcliffe, Adaptimmune Chief Executive Officer. "We have shown a high response rate and these responses are still evolving in many patients with increasing depths of response over time and encouraging durability. I am confident that SPEARHEAD-1 will support our BLA submission next year and offer a life-changing treatment for people with synovial sarcoma."

"Initial data from SPEARHEAD-1 indicate that afami-cel has the potential to offer people with synovial sarcoma a promising new treatment option where there is currently a great unmet medical need," said Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center. "As clinicians, we want to be able to provide a treatment regimen that can help offer a better quality of life."

SPEARHEAD-1 data will be presented at the time of the oral presentation scheduled for June 4th during the sarcoma session taking place from 1:30 p.m. to 4:30 p.m. EDT.

Afami-cel is efficacious and well-tolerated in heavily pre-treated patients based on initial data

At the time of data cut-off (March 29, 2021), 37 patients had received afami-cel (32 with synovial sarcoma, 5 with myxoid/ round cell liposarcoma [MRCLS])
Of the 37 patients who had received afami-cel, 4 patients were pending first efficacy assessment, and 33 had at least one scan as of data cut off (29 with synovial sarcoma, 4 with MRCLS)
The overall response rate1 was 39.3% (13/33), 41.4% (12/29) for synovial sarcoma; 25.0% (1/4) for MRCLS
Of the 29 patients with synovial sarcoma with at least one scan, 2 had complete responses (CRs), 10 had partial responses (PRs), 13 had stable disease (SD), 4 had progressive disease (PD)
The disease control rate for people with synovial sarcoma was 86.2% (25/29) (defined as either response or stable disease)
Of the 4 patients with MRCLS with at least one scan, 1 patient had a partial response, 2 had stable disease, and 1 had progressive disease
Objective responses have been reported across a wide range of cell doses and MAGE-A4 antigen expression levels
Initial durability data is encouraging, and the median duration of response has not been reached
To date, the safety profile of afami-cel has been favorable, with mainly low-grade cytokine release syndrome and tolerable/reversible hematologic toxicities.
Overview of SPEARHEAD-1 trial design
SPEARHEAD-1 is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Compelling clinical responses in patients with synovial sarcoma were previously reported with afami-cel in a Phase 1 trial (CTOS 2020).

Approximately 90 patients are planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete, and Cohort 2 is currently recruiting. The primary efficacy analysis will be for Cohort 1 only, which will be used to support the BLA filing next year. No formal hypothesis testing is planned for Cohort 2. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses.

Eligible patients were ≥ 16 and < 75 years, HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells that were ≥ 2+ by immunohistochemistry. Eligible patients received afami-cel doses between 1–10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy.

The primary endpoint is overall response rate per RECIST v1.1 by independent review. The primary endpoint will be evaluated using a one-sided exact-based Clopper-Pearson 97.5% confidence interval (CI). If the lower bound of the CI exceeds the response rate reported with historical second line therapy(ies), the trial will have met the pre-specified threshold for demonstrating efficacy.

An independent Data Safety Monitoring Board reviews ongoing safety and benefit:risk during the interventional phase of the trial.

On May 19, 2021 Adagene Inc. (‘Adagene’) (Nasdaq: ADAG), a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported clinical data from its ADG106 NEObodyTM program (Press release, Adagene, MAY 19, 2021, View Source [SID1234580333]). Results from Phase I, open-label, dose-escalation, single center (NCT03802955) and multicenter (NCT03707093) studies of ADG106 in subjects with advanced or metastatic solid tumors and/or relapsed/refractory non-Hodgkin lymphoma were presented in an abstract at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting . In these Phase I trials, ADG106 monotherapy exhibited a favorable safety profile and demonstrated promising clinical efficacy in biomarker positive patients. ADG106 is a fully human, ligand-blocking, agonistic anti-CD137 IgG4 antibody (mAb) engineered using Adagene’s proprietary NEObody platform technology.

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‘We are very pleased with the original finding of a predictive biomarker for our anti-CD137 agonist and its association with tumor shrinkage,’ said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. ‘ADG106 has been well tolerated in dose escalation and extensive expansion cohorts at dosage of up to 5 mg/kg, which exceeds that of other anti-CD137 agonists. Further, this clinical data demonstrates the power of our proprietary NEObody platform designed to generate antibodies with novel mechanisms of action by targeting unique and highly conserved epitopes. We believe these results, together with analyses of PK and PD data from around 100 patient population, support the recommended dose regimen for ongoing clinical development of ADG106 as monotherapy and in combination with anti-PD-1 and other therapies. We look forward to multiple upcoming studies as we continue to advance our ADG106 clinical program.’

‘Predictive biomarkers for patient stratification are critical to advances in precision immuno-oncology. It’s compelling to identify a predictive biomarker for anti-CD137 agonism that shows a strong correlation between ADG106 treatment and tumor shrinkage,’ said Hua Gong, M.D. Ph.D., Chief Operating Officer and Head of Precision Medicine of Adagene. ‘In an upcoming global Phase Ib/II trial (ADG106-2001), we plan to enrich for populations expressing our predictive biomarker in order to demonstrate a clinical benefit to ADG106 therapy. Our predictive biomarker has the potential to optimize favorable treatment options and enable oncologists to preselect cancer patients who are likely to benefit from ADG106 treatment. In our continuing commitment to the development of precision immunotherapies, Adagene has established a center of excellence for precision medicine in San Diego with cutting-edge technologies to support biomarker-guided clinical trials.’

Interim data for the ongoing Phase 1 clinical trial includes:

·Biomarker studies: In a retrospective analysis, 75% of biomarker positive patients demonstrated more than 30% tumor shrinkage after ADG106 treatment.
oTumor shrinkage was not significant among biomarker negative patients. There was a strong negative correlation (100%) between biomarker absence and clinical response.
oA tissue microarray study confirmed biomarker expression in a variety of tumor types suggesting a broad indication for ADG106 therapy.
·Target engagement: Target engagement upon ADG106 treatment was demonstrated with dose-dependent increases in NK cells in ADG106-mediated anti-tumor activities and in dose-dependent induction of soluble CD137 over baseline.
·Safety and efficacy: ADG106 demonstrated a disease control rate of 56% and exhibited a favorable safety profile at 3mg/kg and 5mg/kg with dose escalation up to 10mg/kg.
ADG106-1001 and ADG106-1002 Phase I trials have successfully completed enrollment of nearly 100 patients with advanced solid tumors and/or non-Hodgkin’s lymphoma in the US and China, respectively. Limited TEAEs, i.e., liver toxicity or hematologic abnormalities, were observed. Following a productive end-of-phase I (EOP1) meeting about our ADG106 biomarker-stratified trial design with the FDA, Adagene made a new submission (ADG106-2001) to stratify patients using the predictive biomarker prior to treatment with ADG106 as monotherapy and its combination with anti-PD-1 therapy. In March 2021, Adagene initiated patient enrollment in China for ADG106-1008 (NCT04775680) a multicenter, open-label, Phase Ib/II study of ADG106 in combination with PD-1 antibody in advanced solid tumors and relapsed/refractory non-Hodgkin lymphoma. Preparations are underway for the ADG106-1003 trial in Australia to evaluate ADG106 in combination with other therapies in advanced solid tumors and hematological malignancies.

On May 19, 2021 Aadi Bioscience ("Aadi"), a privately-held biopharmaceutical company focusing on precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported the release of an abstract selected for poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting being held virtually on June 4-8, 2021 (Press release, Aadi, MAY 19, 2021, View Source [SID1234580332]). The poster presentation will highlight antitumor activity in a subset of patients with TSC1 or TSC2 alterations and neoplasms other than advanced malignant PEComa who were treated with single-agent nab-sirolimus (FYARRO) in an expanded access program (NCT03817515). Details on the abstract are summarized below.

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Abstract Title: Institutional experience with nab-sirolimus in patients with malignancies harboring TSC1 or TSC2 mutations
Abstract Number: 3111
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Session Date and Time: June 4, 2021 at 9 AM CT

On May 19, 2021 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported that its Board of Directors has authorized a quarterly cash dividend of $0.26 per common share, payable on July 15, 2021, to shareholders of record as of June 15, 2021 (Press release, Thermo Fisher Scientific, MAY 19, 2021, View Source [SID1234580331]).

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On May 19, 2021 Blueprint Medicines Corporation (NASDAQ: BPMC) reported the presentation of updated Phase 1/2 ARROW trial data demonstrating durable clinical benefits of GAVRETO (pralsetinib) in metastatic RET fusion-positive non-small cell lung cancer (NSCLC) and other advanced solid tumors (Press release, Blueprint Medicines, MAY 19, 2021, View Source [SID1234580330]). GAVRETO showed high response rates in treatment-naïve patients with RET fusion-positive NSCLC, clinical activity across a number of RET fusion-positive tumor types and a safety profile consistent with previously reported results. These data will be presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 4-8.

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"Precision therapies have significantly improved outcomes in non-small cell lung cancer driven by actionable biomarkers, and these pralsetinib data show the transformative impact of targeting RET alterations in the front-line treatment setting," said Giuseppe Curigliano, M.D., Ph.D., Associate Professor of Medical Oncology at the University of Milano and the Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy. "In treatment-naïve metastatic NSCLC, these results are particularly encouraging, with many patients remaining in response. The data highlight the critical importance of identifying RET alterations before initiating treatment, so that more patients have the opportunity to benefit from targeted therapy."

"Updated data in metastatic RET fusion-positive non-small cell lung cancer underscore how GAVRETO may transform the standard of care, including in the first-line treatment setting," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "The results in treatment-naïve patients with RET fusion-positive NSCLC reflect the compelling clinical profile of GAVRETO, with high response rates and durability of response that have strengthened over time. In other RET-altered cancers, target lesions were reduced across a diverse range of tumor types, with the majority of patients responding to treatment. In collaboration with Genentech, we look forward to engaging with the FDA based on the strength of these data in metastatic RET fusion-positive solid tumors."

Clinical Activity Data

The ASCO (Free ASCO Whitepaper) data included response-evaluable populations comprising 216 patients with RET fusion-positive NSCLC who had measurable disease at baseline and received a starting GAVRETO dose of 400 mg once daily, and 19 patients with other RET fusion-positive solid tumors, as of a date cutoff date of November 6, 2020. Tumor response was assessed by blinded independent central review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and all responses were confirmed.

RET Fusion-Positive NSCLC

With a median follow-up of 17.1 months, GAVRETO showed durable clinical benefits in patients with RET fusion-positive NSCLC with or without prior therapy. In 68 treatment-naïve patients, the overall response rate (ORR) was 79 percent (95% CI: 68%, 88%). The complete response (CR) rate was 6 percent, 10 percent of patients had complete regression of target tumors, and 74 percent of patients had a partial response (PR). The median duration of response (DOR) was not reached (95% CI: 9.0 months, not reached).

For treatment-naïve patients, the initial study protocol limited enrollment to those determined by the investigator to be ineligible for standard platinum-based chemotherapy, which may be due to age, comorbidities or other poor prognostic factors. This eligibility restriction was removed in July 2019, with the goal of including a population more reflective of real-world practice. In an exploratory analysis of treatment-naïve patients enrolled after this expansion of inclusion criteria (n=25), the ORR was 88 percent (95% CI: 69%, 98%), and all responses were PRs.

In 126 patients who previously received platinum-based chemotherapy, the ORR was 62 percent (95% CI: 53%, 70%). The CR rate was 4 percent, 12 percent of patients had complete regression of target tumors, and 58 percent of patients had a PR. The median DOR was 22.3 months (95% CI: 15.1 months, not reached).

Other RET Fusion-Positive Solid Tumors

In a heavily pre-treated patient population who had a median follow-up of 12.1 months, GAVRETO showed clinical activity across multiple additional RET-driven tumor types. In 19 patients with a variety of RET fusion-positive solid tumors beyond NSCLC and thyroid cancer, the ORR was 53 percent (95% CI: 29%, 76%) and the median DOR was 19.0 months (95% CI: 5.5 months, not estimable). Tumor reductions were shown in patients with the following cancers – pancreatic, cholangiocarcinoma, colon, lung (except NSCLC), mesenchymal, salivary duct, sweat gland and thymus – as well as patients diagnosed with cancers of unknown primary origin. In the three patients with pancreatic cancer, a particularly difficult-to-treat tumor type, there was one CR and two PRs.

Safety Data

As of a data cutoff date of November 6, 2020, a total of 471 patients were enrolled with a GAVRETO dose starting at 400 mg once daily. Across tumor types, GAVRETO was well-tolerated with no new safety signals observed. The most common treatment-related adverse events (AEs) reported by investigators (≥20 percent) were neutropenia, increased aspartate aminotransferase (AST), anemia, decreased white blood cell count, increased alanine aminotransferase (ALT), hypertension, constipation and asthenia. Overall, 6 percent of patients discontinued GAVRETO due to treatment-related AEs.

These updated data will be reported in two ASCO (Free ASCO Whitepaper) poster presentations: one on RET fusion-positive NSCLC (Abstract #9089) and one on RET fusion-positive solid tumors (Abstract #3079). Copies of the data presentations will be available starting June 4, 2021 in the "Science―Publications and Presentations" section of Blueprint Medicines’ website.

About GAVRETO (pralsetinib)

GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA approved test, adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and adults and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). These indications are approved under accelerated approval based on ORR and DOR. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. In addition, GAVRETO is approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with locally advanced or metastatic RET fusion-positive NSCLC after platinum-based chemotherapy.

GAVRETO is not approved for the treatment of any other indication in the U.S. by the FDA or in China by the NMPA, or for any indication in any other jurisdiction by any other health authority.

GAVRETO is designed to selectively and potently target oncogenic RET alterations, including secondary RET mutations predicted to drive resistance to treatment. In preclinical studies, GAVRETO inhibited RET at lower concentrations than other pharmacologically relevant kinases, including VEGFR2, FGFR2 and JAK2. For more information, visit GAVRETO.com.

Blueprint Medicines and Roche are co-developing GAVRETO globally (excluding Greater China) for the treatment of patients with RET-altered NSCLC, various types of thyroid cancer and other solid tumors. The European Medicines Agency validated a marketing authorization application for GAVRETO for the treatment of RET fusion-positive NSCLC. The FDA granted breakthrough therapy designation to GAVRETO for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of GAVRETO in Greater China, which encompasses Mainland China, Hong Kong, Macau and Taiwan.

Enrollment is ongoing in the Phase 1/2 ARROW trial, including for patients with various RET fusion-positive solid tumors, and in the Phase 3 AcceleRET Lung trial for treatment-naïve patients with RET fusion-positive NSCLC. For more information about GAVRETO clinical trials, visit www.clinicaltrials.gov or www.blueprintclinicaltrials.com.

About RET-Altered Solid Tumors

RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and multiple types of thyroid cancer. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET fusions are observed at low frequencies in colorectal, breast, pancreatic and other cancers, as well as in patients with treatment-resistant EGFR-mutant NSCLC.