On September 18, 2021 AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that Detailed positive results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the HER2-directed antibody drug conjugate (ADC), demonstrated superior progression-free survival (PFS) versus trastuzumab emtansine (T-DM1), a HER2-directed ADC currently approved to treat patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane (Press release, AstraZeneca, SEP 18, 2021, View Source [SID1234587922]). Results were presented today in a Presidential Symposium at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021.

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At a prespecified interim analysis of DESTINY-Breast03, Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to T-DM1 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p=7.8×10-22). After 15.5 and 13.9 months of follow-up in the Enhertu and T-DM1 arms respectively, the median PFS for patients treated with Enhertu was not reached (95% CI 18.5-NE) compared to 6.8 months for T-DM1 (95% CI 5.6-8.2) as assessed by blinded independent central review (BICR).

In the key secondary endpoint of PFS assessed by investigators, patients treated with Enhertu experienced a three-fold improvement in PFS of 25.1 months versus 7.2 months for T-DM1 (HR 0.26; 95% CI 0.20-0.35; p=6.5×10-24). A consistent PFS benefit was observed in key subgroups of patients treated with Enhertu, including those with a history of stable brain metastases.

There was a strong trend towards improved overall survival (OS) with Enhertu (HR 0.56; 95% CI 0.36-0.86; nominal p=0.007172), however this analysis is not yet mature and is not statistically significant. Nearly all patients treated with Enhertu were alive at one year (94.1%) compared to 85.9% of patients treated with T-DM1.

Confirmed objective response rate (ORR) more than doubled in the Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%). Forty-two (16.1%) complete responses (CR), and 166 (63.6%) partial responses (PR) were observed in patients treated with Enhertu compared to 23 (8.7%) CRs and 67 (25.5%) PRs in patients treated with T-DM1.

Javier Cortés, MD, PhD, Head, International Breast Cancer Center (IBCC), Barcelona, said: "Patients with previously treated HER2-positive metastatic breast cancer will typically experience disease progression in less than a year with available HER2-directed treatments. The high and consistent benefit seen across efficacy endpoints and key subgroups of patients receiving Enhertu in DESTINY-Breast03 is remarkable and supports the potential of Enhertu to become the new standard of care for those who have previously been treated for HER2-positive metastatic breast cancer."

Susan Galbraith, Executive Vice President, Oncology R&D, said: "Today’s results are ground-breaking. Enhertu tripled progression-free survival as assessed by investigators, and provided a disease control rate exceeding 95% compared to 77% for T-DM1 in DESTINY-Breast03. In addition, the safety profile was encouraging with no Grade 4 or 5 interstitial lung disease events in this trial. These unprecedented data represent a potential paradigm shift in the treatment of HER2-positive metastatic breast cancer, and illustrate the potential for Enhertu to transform more patient lives in earlier treatment settings."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The early survival data, which evaluated Enhertu against another HER2-directed ADC, showed that nearly all patients treated with Enhertu were alive after a year and is a positive indication of the potential of this medicine to transform the treatment of HER2-positive metastatic breast cancer. These landmark data will form the basis of our discussions with global health authorities to potentially bring Enhertu to patients with previously treated HER2-positive metastatic breast cancer as a more effective treatment option as soon as possible."

Summary of results: DESTINY-Breast03

Efficacy Measure

Enhertu (5.4 mg/kg)

Total Evaluable (n=261)i

T-DM1 (3.6 mg/kg)

Total Evaluable (n=263)

PFSii (95% CI)

Hazard ratio (95% CI)

0.28 (0.22-0.37)

p-value

p=7.8×10-22

Median PFS (months) (95% CI)ii

NR (18.5-NE)

6.8 months (5.6-8.2)

Landmark 12-month PFS (%) (95% CI)ii

75.8% (69.8-80.7)

34.1% (27.7-40.5)

PFS as assessed by investigators (95% CI)

Hazard ratio (95% CI)

0.26 (0.20-0.35)

p-value

p=6.5×10-24

Median PFS (months) (95% CI)

25.1 months (22.1-NE)

7.2 months (6.8-8.3)

OS

Hazard ratio (95% CI)

0.56 (0.36-0.86)

p-value

p=0.007172iii

Landmark 12-month OS (%) (95% CI)

94.1% (90.3-96.4)

85.9% (80.9-89.7)

Median OS (months) (95% CI)

NE

NE

Confirmed ORR (%) (95% CI)ii,iv

79.7% (74.3-84.4)

34.2% (28.5-40.3)

Complete response (%)

16.1% (42)

8.7% (23)

Partial response (%)

63.6% (166)

25.5% (67)

Stable disease (%)

16.9% (44)

42.6% (112)

Progressive disease (%) (95% CI)

1.1% (3)

17.5% (46)

DCRv

96.6% (252)

76.8% (202)

i Dose used in the study being presented
ii As assessed by blind independent central review
iii Not statistically significant
iv ORR is (CR + PR)
v DCR is (CR+PR+SD)

The safety profile of the most common adverse events with Enhertu in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified. The most common Grade 3 or higher treatment-emergent adverse events in the Enhertu arm were neutropenia (19.1%), thrombocytopenia (7.0%), leukopenia (6.6%) and nausea (6.6%).

There were 27 cases (10.5%) of treatment-related interstitial lung disease (ILD) or pneumonitis reported, as determined by an independent adjudication committee. The majority (9.7%) were low Grade (Grade 1 or Grade 2), with two Grade 3 (0.8%) events reported. No Grade 4 or Grade 5 ILD or pneumonitis events occurred.

DESTINY-Breast01 Updated Results
Updated results from the pivotal DESTINY-Breast01 Phase II trial were also presented at ESMO (Free ESMO Whitepaper) and showed that Enhertu (5.4 mg/kg) continued to demonstrate impressive efficacy and durable responses in patients with HER2-positive metastatic breast cancer following two or more prior HER2-based regimens.

With a median duration of follow-up of 26.5 months, a continued increase in response was seen in patients treated with Enhertu with an updated ORR of 62.0%, including one additional CR (7.1%). A median duration of response (DoR) of 18.2 months was also observed.

The median PFS was 19.4 months. In an exploratory analysis of OS with a median follow-up of 31.1 months, evaluated at a greater maturity (52%), the updated median OS was 29.1 months.

The overall safety and tolerability profile seen with Enhertu in DESTINY-Breast01 continues to be consistent with what has been previously observed. There has been one new case of treatment-related Grade 1 ILD or pneumonitis determined by an independent adjudication committee as of data cut-off of March 26, 2021.

Enhertu is approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting in the US, Japan, the EU and several other countries based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

Several presentations featured during the ESMO (Free ESMO Whitepaper) Congress 2021 will showcase the strength and depth of Enhertu data across multiple tumour types, including gastric, lung and breast cancers, reinforcing the transformational potential of this medicine in the treatment of HER2-targetable cancers.

HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.1 More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 Approximately one in five cases of breast cancer are considered HER2-positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.4

Despite initial treatment with trastuzumab and a taxane, people with HER2-positive metastatic breast cancer will often experience disease progression.5 More effective options are needed to further delay progression and extend survival.5-7

DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary efficacy endpoints include OS, objective response rate, duration of response, clinical benefit rate, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Breast01
DESTINY-Breast01 is a registrational Phase II, single-arm, open-label, global, multi-centre, two-part trial evaluating the safety and efficacy of Enhertu in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with T-DM1.

The primary endpoint of the trial is ORR, as determined by ICR. Secondary objectives include DoR, disease control rate, clinical benefit rate, PFS and OS.

DESTINY-Breast01 enrolled 253 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in Canada, the EU, Israel, Japan, the UK and the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4mg/kg) is also approved in Israel, Japan and the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

In May 2020, Enhertu also received Breakthrough Therapy Designation for the treatment of patients with metastatic NSCLC whose tumours have a HER2-mutation and with disease progression on or after platinum-based therapy.

Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral SERD and potential new medicine AZD9833.

PARP inhibitor, Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, investigating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On September 18, 2021 Ipsen (Euronext: IPN; ADR: IPSEY) reported presentation of new analyses at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 across different forms of cancer for people treated with Cabometyx (cabozantinib) (Press release, Ipsen, SEP 18, 2021, View Source [SID1234587924]). Of note, the final analysis of the pivotal Phase III COSMIC-311 trial (Abstract LBA67) will be presented, with Cabometyx demonstrating a clinically meaningful, sustained efficacy benefit versus placebo in people living with previously treated radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC).

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With a median follow-up of 10.1 months, Cabometyx continued to demonstrate superior median progression-free survival (mPFS) with a reduction in the risk of disease progression or death of 78% versus placebo (hazard ratio [HR]: 0.22, 96% confidence interval [CI]: 0.15-0.32; p<0.0001).1 This final analysis is consistent with data from the interim analysis, presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2021 and published in The Lancet Oncology, (HR: 0.22; 96% CI: 0.13-0.36; p<0.0001).5,6 Further data from the final analysis also confirmed that superior efficacy with Cabometyx was maintained irrespective of previous vascular endothelial growth factor receptor (VEGFR)-targeted therapy.

Efficacy and safety data from the COSMIC-311 interim analysis formed the basis of a type II variation submission to the European Medicines Agency (EMA) for an extension of indication for Cabometyx in RAI-R DTC. On 14 August 2021, the EMA validated the type II variation, confirming the submission is complete and beginning its centralized review process.

The safety profile identified in the COSMIC-311 trial was consistent with that previously observed for cabozantinib and adverse events (AEs) were managed with dose modifications. The discontinuation rate due to treatment-emergent AEs (TEAEs) was 8.8% for Cabometyx vs. 0% for placebo. Grade 3/4 TEAEs occurred in 62% of patients who received Cabometyx vs. 28% for placebo, with no treatment-related grade 5 events.

Steven Hildemann, M.D., Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and Global Patient Safety, Ipsen said "The therapeutic potential of Cabometyx as a key treatment option in our arsenal against a broad range of tumors is continuing to be realized. These final data from the COSMIC-311 trial are a strong example of how Cabometyx can make a tangible difference to the lives of people living with cancer and we look forward to receiving a decision from the EMA next year. We are committed to further evaluating the role Cabometyx may continue to play against difficult-to-treat cancers as we also look towards the results of the ongoing Phase III trials in non-small cell lung cancer (CONTACT-01) and metastatic castration-resistant prostate cancer (CONTACT-02)."

Additional data to be presented at ESMO (Free ESMO Whitepaper) featuring Cabometyx include new results from cohort 6 of the COSMIC-021 Phase Ib trial evaluating the combination of Cabometyx and atezolizumab in people living with previously treated metastatic castration-resistant prostate cancer (mCRPC) (Abstract LBA24).2 These additional analyses build on the interim data presented at ASCO (Free ASCO Whitepaper) 2020,7 with an expanded cohort 6 of 132 patients evaluated.2 With a median follow-up of 15.2 months, the primary endpoint of objective response rate (ORR) assessed by investigator per RECIST 1.1 (response evaluation criteria in solid tumours) was 23%, with three patients demonstrating a complete response (CR).2

Prof. Dr. Gunhild von Amsberg, University Medical Center Hamburg-Eppendorf (UKE) and investigator in the CONTACT-02 trial, said "As a uro-oncologist, I am encouraged by the results presented at this year’s ESMO (Free ESMO Whitepaper) congress. For people living with advanced metastatic castration-resistant prostate cancer, the prognosis is often poor and the potential of new innovative therapies is critically important. Based on these clinically meaningful results of Cabometyx plus atezolizumab from cohort 6 of the COSMIC-021 trial, we now look forward to the results of the ongoing Phase III CONTACT-02."

Further analyses from the landmark Phase III CheckMate -9ER trial investigating the combination of Cabometyx and nivolumab were are also being presented at ESMO (Free ESMO Whitepaper), providing additional evidence to inform clinical decision-making in advanced renal cell carcinoma (RCC). New data demonstrated improved efficacy for Cabometyx and nivolumab regardless of prior nephrectomy status, when measured by PFS, ORR, CR and response durability outcomes, versus sunitinib (Abstract 663P).3 Additionally, a matching-adjusted indirect comparison analysis is being presented, demonstrating superior, statistically significant differences in health-related quality of life across all outcomes analysed in favour of Cabometyx and nivolumab versus the combination of axitinib and pembrolizumab (Abstract 668P).4

More information on these data can be found during the presentation sessions outlined below:

Title Date and time
Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC): results of expanded cohort 6 of the COSMIC-021 Study
Saturday 18 September

13:30-13:40 CEST

Cabozantinib Versus Placebo in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer (DTC) Who Have Progressed After Prior VEGFR-Targeted Therapy: Updated Results From the Phase 3 COSMIC-311 Trial
Monday 20 September

17:30-17:35 CEST

First-line nivolumab + cabozantinib (NIVO+CABO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in subgroups based on prior nephrectomy in the CheckMate 9ER trial Poster presentation – Available on-demand beginning September 16 at 8:30 am CEST
Matching-adjusted indirect comparison (MAIC) of health-related quality of life (HRQoL) of nivolumab plus cabozantinib (N+C) vs pembrolizumab plus axitinib (P+A) in previously untreated advanced renal cell carcinoma (aRCC) Poster presentation – Available on-demand beginning September 16 at 8:30 am CEST

References

Capdevila et al., ESMO (Free ESMO Whitepaper) 2021. Cabozantinib (C) versus placebo (P) in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy: updated results from the phase 3 COSMIC-311 trial and prespecified subgroup analyses based on prior VEGFR-targeted therapy
Agarwal et al., ESMO (Free ESMO Whitepaper) 2021. Cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): primary analysis of cohort 6 of the COSMIC-021 study
Porta et al., ESMO (Free ESMO Whitepaper) 2021. First-line nivolumab + cabozantinib (NIVO+CABO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in subgroups based on prior nephrectomy in theCheckMate 9ER trial
Porta et al., ESMO (Free ESMO Whitepaper) 2021. Matching-adjusted indirect comparison (MAIC) of health-related quality of life (HRQoL) of nivolumab plus cabozantinib (N+C) vs pembrolizumab plus axitinib (P+A) in previously untreated advanced renal cell carcinoma (aRCC)
Brose et al., ASCO (Free ASCO Whitepaper) 2021. Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: results from the phase 3 COSMIC-311 trial.
Brose et al., Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncology. 2021; 22:8. DOI:View Source(21)00332-6
Agarwal et al., ASCO (Free ASCO Whitepaper) 2020. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: Results of cohort 6 of the COSMIC-021 study.

On September 18, 2021 Epic Sciences, Inc.’s (Epic) Comprehensive Cancer Profiling Platform continues to deliver compelling cell analysis information in clinical trials as data being reported at the virtual European Society for Medical Oncology Congress 2021 (ESMO 2021) demonstrate (Press release, Epic Sciences, SEP 18, 2021, View Source [SID1234587939]).

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Data from abstract 577O – "PRINCE: Interim analysis of the phase Ib study of 177Lu-PSMA-617 in combination with pembrolizumab for metastatic castration resistant prostate cancer (mCRPC)," being presented by Shahneen K. Sandhu, MD, principal investigator of PRINCE and Associate Professor at the Peter MacCallum Cancer Centre, Victoria, Australia, shows that the majority of patients’ circulating tumor cells (CTCs) expressing the target Prostate-Specific Membrane Antigen (PSMA) at baseline were cleared at 12 weeks ,when measured using the Epic PSMA CTC Assay – prior to other response biomarkers in the study.

"CTCs provide a non-invasive tool to track drug-target engagement," said Dr. Sandhu. "This approach could provide complementary information to PET imaging, so that active treatment combinations can be identified in other early phase trials." Biomarker analysis is ongoing in this and other studies comparing the Epic Sciences PSMA CTC Assay with PSMA and FDG PET imaging, and patient outcomes.

The capabilities of Epic’s Comprehensive Cancer Profiling Platform are also highlighted in two ESMO (Free ESMO Whitepaper) 2021 posters with leading global collaborators:

Abstract 613P – Chromosomal instability (CIN) biomarker in circulating tumor cells (CTC) may predict for therapy resistance in mCRPC.

Abstract 614P – Circulating tumor cell (CTC) morphologic sub-types present prior to treatment in the CARD trial identify therapy resistance.

On September 17, 2021 Midatech Pharma PLC (AIM: MTPH.L; NASDAQ: MTP), a drug delivery technology company focused on improving the bio-delivery and biodistribution of medicines, reported its unaudited interim results for the six months ended 30 June 2021 (Press release, Midatech Pharma, SEP 17, 2021, View Source [SID1234587890]).

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OPERATIONAL HIGHLIGHTS

On 17 June 2021, the Company announced significant progress across a number of R&D programmes including:

Q-Sphera

·Breakthrough data on the successful encapsulation of an exemplar monoclonal antibody (mAb);

·The delivery of proof of concept formulations of MTX214 and MTX216 to the Company’s collaboration partner for the partner’s in vivo studies; and

·The successful development of MTD211, a long-acting formulation of brexpiprazole which, in in vivo studies, demonstrated therapeutic blood levels over a period of three months.

MTX110

·Demonstration, in vitro, of the potency of MTX110 in four patient-derived Glioblastoma cell lines.

FINANCIAL HIGHLIGHTS (including post period end)

·Total revenue in H1 2021 was £0.40m (1H20: £0.17m). Total revenue represents income from R&D collaborations plus grant revenue.

·Research and development costs decreased by 50% to £2.01m (1H20: £3.99m) as a result of the termination of MTD201 and focus on multiple earlier stage programmes.

·Administrative expenses decreased 44% to £1.64m (1H20: £2.93m) due to expenses incurred in connection with the Strategic Review and restructuring in the prior period.

·Net cash used in operating activities (after changes in working capital) in 1H21 was £3.11m, compared with £7.09m in 1H20.

·In July, post period end, the Company raised £10.0m before expenses in an UK Placing of 35.1m ordinary shares at £0.285 per share.

·The cash balance on 30 June 2021 was £4.20m.
.
Commenting, Stephen Stamp, CEO and CFO of Midatech said: "We are pleased to report good progress throughout the Company and an expanded and exciting pipeline of programmes and opportunities. The disruption and costs of the restructuring in 2020 are now behind us. The first half of 2021 has been highly productive with three potentially viable Q-Sphera formulations, one internal and two for a collaboration partner. We believe the breakthrough data on the encapsulation of a protein could prove to be a very significant opportunity for Midatech."

The Company will be hosting a webinar at 5.30pm BST / 12.30pm EST on Monday 20 September 2021. The webinar is open to all existing and potential shareholders and those interested in attending may register via the following link where, following registration, they will be provided with access details:

View Source

Participants may submit questions during the webinar or in advance via email to: [email protected]

This announcement contains inside information for the purposes of Article 7 of the Market Abuse Regulation (EU) 596/2014 as it forms part of UK domestic law by virtue of the European Union (Withdrawal) Act 2018 ("MAR"), and is disclosed in accordance with the company’s obligations under Article 17 of MAR.

On September 17, 2021 Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported the interim analysis results of the Phase 3 ORIENT-16 study evaluating sintilimab in combination with chemotherapy compared to chemotherapy alone for the first-line treatment of advanced or metastatic gastric or gastroesophageal junction adenocarcinoma in an oral presentation at the ESMO (Free ESMO Whitepaper) (European Society for Medical Oncology) Congress 2021 (Abstract # LBA53) (Press release, Innovent Biologics, SEP 17, 2021, View Source [SID1234587908]).

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As of the June 20, 2021 data cutoff date for the interim analysis, 650 patients have been enrolled. Sintilimab in combination with chemotherapy (oxaliplatin and capecitabine) demonstrated superior overall survival (OS) compared to placebo plus chemotherapy, with a 34.0% reduction in the risk of death (HR 0.660; 95%CI, 0.505-0.864; p=0.0023) and a 5.5-month improvement in median OS (18.4 months vs. 12.9 months) in patients with CPS ≥5, and 23.4% reduction in the risk of death and a 2.9-month improvement in mOS (15.2 months vs. 12.3 months) in all randomized patients (the ITT population). The OS benefits were consistent in all prespecified subgroup analyses. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy.

The principal investigator of the ORIENT-16 study, Prof. Jianming Xu from the Fifth Medical Center of People’s Liberation Army General Hospital, stated, "ORIENT-16 is the first Phase 3 clinical trial in China to demonstrate an anti-PD-1 antibody in combination with chemotherapy significantly prolonged overall survival in the first-line treatment of advanced gastric cancer. Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China. The prognosis of advanced gastric cancer is very poor. The results of the ORIENT-16 study have the potential to bring a new treatment option to people with gastric cancer."

Dr. Zhou Hui, Senior Vice President of Innovent, stated, "While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet in gastric cancer. The treatment options for advanced gastric cancer are very limited and the ORIENT-16 study aimed to help address this unmet medical need. These results are very encouraging and confirmed the clinical value of sintilimab plus chemotherapy in the first-line treatment of advanced gastric cancer. We are grateful for all the contributions made by every investigator and patient in this study, and we hope that sintilimab can become a new treatment option for people with gastric cancer. Innovent planned to file a supplemental new drug application to the National Medical Products Administration (NMPA) in China based on the results of interim analysis. Up until now, sintilimab has demonstrated improved survival in the first-line treatment of five major types of cancer – nonsquamous non-small cell lung cancer, squamous non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer."

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint was overall survival, in all randomized and in PD-L1 positive patients.

About Gastric Cancer

Gastric cancer is one of the most common malignant tumor types worldwide. According to GLOBOCAN estimates, there were approximately one million new cases and 769,000 new deaths of gastric cancer in 2020, making it the fifth most common cancer and third leading cause of cancer death globally. About half of all gastric cancer cases occurred in East Asia, mainly in China. The first-line treatment of advanced gastric cancer remains limited. Currently, the five-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent, and the median overall survival is approximately one year.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has three clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
In combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.