On October 23, 2023 Astrazeneca and Daiichi Sankyo reported positive results from the primary analysis of the ongoing DESTINY-PanTumor02 Phase II trial showed that Enhertu (trastuzumab deruxtecan) continued to demonstrate clinically meaningful and durable responses, leading to a clinically meaningful survival benefit in previously treated patients across multiple HER2-expressing advanced solid tumours (Press release, AstraZeneca, OCT 23, 2023, View Source [SID1234636266]).

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These results, which include the first progression-free survival (PFS) and overall survival (OS) findings reported from the trial, were presented today at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (abstract #LBA34) in Madrid, Spain and simultaneously published in the Journal of Clinical Oncology.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

In the primary analysis, Enhertu demonstrated a median PFS of 6.9 months (95% confidence interval [CI] 5.6-8.0) and a median OS of 13.4 months (95% CI 11.9-15.5) in the overall trial population of previously treated patients with HER2-expressing advanced solid tumours, including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic cancers or other tumours, as assessed by investigator. Enhertu also continued to show a confirmed objective response rate (ORR) of 37.1% and a median duration of response (DoR) of 11.3 months (95% CI 9.6-17.8) in these patients.

Funda Meric-Bernstam, MD, Chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, US and principal investigator for the trial, said: "These primary analysis results confirm the efficacy shown at an interim analysis of the DESTINY-PanTumor02 trial, with responses leading to clinically meaningful survival outcomes across a broad range of HER2-expressing solid tumours. Based on these results, Enhertu has the potential to change the course of disease for certain patients with HER2-expressing advanced cancers who have limited treatment options and currently no approved HER2-directed therapies."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "These updated data from DESTINY-PanTumor02 continue to illustrate the importance of HER2 as an actionable biomarker across a range of studied solid tumour types. Enhertu has the potential to offer improved outcomes for specific patients with previously treated HER2-expressing cancers, and we hope to bring this important medicine to patients as quickly as possible."

Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: "Improving survival outcomes for patients is one of the primary goals of cancer treatment and the clinically meaningful progression-free and overall survival results seen in DESTINY-PanTumor02 are encouraging. These results provide additional evidence for Enhertu to potentially become the first antibody drug conjugate approved in a tumour-agnostic setting in patients whose tumours express HER2."

Summary of results: DESTINY-PanTumor02 primary analysis

Efficacy measure

Endometrial

Cervical

Ovarian

Bladder

Otheri

BTC

Pancreatic

All patients

All IHC expression Levels

(n)

40

40

40

41

40

41

25

267

Confirmed ORR (%)

(95% CI)

57.5%

50.0%

45.0%

39.0%

30.0%

22.0%

4.0%

37.1%

Median DoR (months) (95% CI)

NR

(9.9-NR)

14.2

(4.1-NR)

11.3

(4.1-22.1)

8.7

(4.3-11.8)

22.1

(4.1-NR)

8.6

(2.1-NR)

5.7

(NR-NR)

11.3

(9.6-17.8)

Median PFS (months) (95% CI)

11.1

(7.1-NR)

7.0

(4.2-11.1)

5.9

(4.0-8.3)

7.0

(4.2-9.7)

8.8

(5.5-12.5)

4.6

(3.1-6.0)

3.2

(1.8-7.2)

6.9

(5.6-8.0)

Median OS (months) (95% CI)

26.0

(12.8-NR)

13.6 (11.1-NR)

13.2

(8.0-17.7)

12.8 (11.2-15.1)

21.0

(12.9-24.3)

7.0

(4.6-10.2)

5.0

(3.8-14.2)

13.4

(11.9-15.5)

IHC 3+

(n)

13

8

11

16

9

16

2

75

Confirmed ORR (%)

(95% CI)

84.6%

75.0%

63.6%

56.3%

44.4%

56.3%

0.0%

61.3%

Median DoR (months) (95% CI)

22.1

(9.6-NR)

Median PFS (months) (95% CI)

NR

(7.3-NR)

NR

(3.9-NR)

12.5

(3.1-NR)

7.4

(3.0-11.9)

23.4

(5.6-NR)

7.4

(2.8-12.5)

5.4

(2.8-NR)

11.9

(8.2-13.0)

Median OS (months) (95% CI)

26.0

(18.9-NR)

NR

(3.9-NR)

20.0

(3.8-NR)

13.4

(6.7-19.8)

24.3 (11.1-NR)

12.4

(2.8-NR)

12.4

(8.8-NR)

21.1

(15.3-29.6)

IHC 2+

(n)

17

20

19

20

16

14

19

125

Confirmed ORR (%)

(95% CI)

47.1%

40.0%

36.8%

35.0%

18.8%

0.0%

5.3%

27.2%

Median DoR (months) (95% CI)

9.8

(4.3-12.6)

Median PFS (months) (95% CI)

8.5

(4.6-15.1)

4.8

(2.7-5.7)

4.1

(2.3-12.6)

7.8

(2.6-11.6)

5.5

(2.8-8.7)

4.2

(2.8-6.0)

2.8

(1.4-9.1)

5.4

(4.2-6.0)

Median OS (months) (95% CI)

16.4

(8.0-NR)

11.5

(5.1-NR)

13.0

(4.7-21.9)

13.1 (11.0-19.9)

14.6

(6.8-22.4)

6.0

(3.7-11.7)

4.9

(2.4-15.7)

12.2

(10.7-13.5)

BTC, biliary tract cancer; CI, confidence interval; DoR, duration of response; IHC, immunohistochemistry; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival
Analysis of ORR by investigator was performed in patients who received ≥1 dose of T-DXd; all patients (n=267; including 67 patients with IHC 1+ [n=25], IHC 0 [n=30], or unknown IHC status [n=12] by central testing) and patients with centrally confirmed HER2 IHC 3+ (n=75) or IHC 2+ (n=125) status.
Analysis of DoR was performed in patients with objective response who received ≥1 dose of T-DXd; all patients (n=99; including 19 patients with IHC 1+ [n=6], IHC 0 [n=9], or unknown IHC status [n=4] by central testing) and patients with centrally confirmed HER2 IHC 3+ (n=46) or IHC 2+ (n=34) status.
iResponses in extramammary Paget disease, head and neck cancer, oropharyngeal neoplasm, and salivary gland cancer.

At the primary analysis of the DESTINY-PanTumor02 trial, a greater response rate continued to be seen in patients with the highest level of HER2-expression (immunohistochemistry (IHC) 3+) as confirmed by central testing, where Enhertu demonstrated a confirmed ORR of 61.3% (95% CI: 49.4-72.4) as part of an exploratory analysis. Enhertu demonstrated a median PFS of 11.9 months (95% CI: 8.2-13.0) and a median OS of 21.1 months (95% CI: 15.3-29.6) in patients with IHC 3+ tumour expression, with a median DoR of 22.1 months (95% CI: 9.6-NR) achieved in this patient population. These clinically meaningful outcomes reinforce results from an interim analysis of the trial presented earlier this year at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified. The most common Grade 3 or higher treatment-emergent adverse events (TEAEs) were neutropenia (19.1%), anaemia (10.9%), fatigue (7.1%) and thrombocytopenia (5.6%).

In DESTINY-PanTumor02, 28 patients (10.5%) experienced interstitial lung disease (ILD) or pneumonitis related to treatment with Enhertu as determined by an independent adjudication committee. The majority (9.0%) were low-grade (Grade 1 or 2) with one (0.4%) Grade 3 event, no Grade 4 events and three (1.1%) Grade 5 events observed.

Notes

HER2 expression in solid tumours
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.1,2 In some cancers, HER2 expression is amplified or the cells have activating mutations.1,3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.4

While HER2-directed therapies have been used to treat breast, gastric, lung and colorectal cancers, more research is needed evaluating their potential role in treating other HER2-expressing solid tumour types.2,5,6

HER2 is an emerging biomarker in solid tumour types including biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.3 Testing is not routinely performed in these additional tumour types and as a result, available literature is limited. HER2 overexpression (IHC3+) has been observed at rates from 1% to 28% in these solid tumours.7,8 There is an unmet need for effective therapies for certain HER2-expressing solid tumours, particularly for those who have progressed on or are refractory to standard of care therapies as there are currently no approved HER2-directed therapies for these cancers.2,9

DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of previously treated HER2-expressing tumours, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer or other tumours.

The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed ORR as assessed by investigator. Secondary endpoints include DoR, disease control rate, PFS, OS, safety, tolerability and pharmacokinetics.

DESTINY-PanTumor02 has enrolled 267 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 number of topoisomerase I inhibitor payloads, (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) is approved in more than 55 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH]-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in more than 30 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.

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

On October 23, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for rare and ultrarare diseases, reported the closing of its previously announced underwritten public offering of 9,833,334 shares of its common stock, including the exercise in full by the underwriters of their option to purchase an additional 1,500,000 shares, at a price to the public of $30.00 per share, and, to certain investors in lieu of common stock, pre-funded warrants to purchase 1,666,722 shares of its common stock at a purchase price of $29.999 per pre-funded warrant, which equals the public offering price per share of the common stock less the $0.001 exercise price per share of each pre-funded warrant (Press release, Ultragenyx Pharmaceutical, OCT 23, 2023, View Source [SID1234636262]). The estimated net proceeds to the company, after deducting underwriting discounts and commissions and other offering expenses payable by the company, were approximately $326.1 million.

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J.P. Morgan, Goldman Sachs & Co. LLC, BofA Securities, and TD Cowen acted as joint book-running managers for the offering.

The securities described above were offered by Ultragenyx Pharmaceutical Inc. pursuant to a registration statement previously filed with the Securities and Exchange Commission that became automatically effective on February 12, 2021. A final prospectus supplement and accompanying prospectus were filed with the SEC and available for free on the SEC’s website at View Source Copies of the final prospectus supplement and the accompanying prospectus related to the offering may be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at 866-803-9204, or by email at prospectus- [email protected]; Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 212-902-9316 or by emailing [email protected]; BofA Securities, NC1-002-02-25, 201 North Tryon Street, Charlotte, NC 28255-0001, Attention: Prospectus Department, or by email at [email protected]; and Cowen and Company, LLC, 599 Lexington Avenue, New York, NY 10022, by email at [email protected] or by telephone at (833) 297-2926.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On October 23, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported a trial-in-progress poster from the Phase 1/2 clinical trial for SNS-101, a conditionally active, human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation), at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) 2023 (Press release, Sensei Biotherapeutics, OCT 23, 2023, View Source [SID1234636261]).

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The multi-center Phase 1/2 clinical trial is a first-in-human, open-label, dose escalation study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of SNS-101 as both a monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo in patients with advanced solid tumors. To date, four patient cohorts have been enrolled in the monotherapy arm. Sensei expects to report initial pharmacokinetic and safety monotherapy data in the fourth quarter of 2023, and topline monotherapy data in 2024. The company has also initiated the combination arm of the study and expects to report initial combination safety and pharmacokinetic data in the first quarter of 2024, with preliminary anti-tumor activity combination data in 2024.

The full poster is available for viewing on Sensei’s website in the "Events & Presentations" section of the Company’s Investor Relations website at www.senseibio.com.

On October 23, 2023 Revolution Medicine presented its corporate presentation (Press release, Revolution Medicines, OCT 23, 2023, View Source [SID1234636260]).

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On October 23, 2023 Quince Therapeutics, Inc. (Nasdaq: QNCX), a late-stage biotechnology company developing an innovative drug delivery technology that leverages a patient’s own biology to deliver rare disease therapeutics, reported the successful completion of its acquisition of EryDel S.p.A., a privately-held, late-stage biotech company (Press release, Quince Therapeutics, OCT 23, 2023, View Source [SID1234636259]). Quince’s newly acquired Phase 3 lead asset, EryDex, targets a rare neurodegenerative disease, Ataxia-Telangiectasia (A-T). Currently, there are no approved treatments for A-T and the market represents a $1+ billion estimated peak sales opportunity globally. EryDex utilizes a highly differentiated and proprietary technology platform for autologous intracellular drug encapsulation (AIDE), which is designed to optimize the biodistribution of dexamethasone sodium phosphate (DSP; a pro-drug) by using an A-T patient’s own red blood cells to deliver the sustained therapeutic over a once monthly treatment period.

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"The successful closing of the EryDel acquisition is an exciting step forward in fulfilling our vision to build a leading rare disease biotechnology company," said Dirk Thye, M.D., Quince’s Chief Executive Officer. "We are dedicated to developing treatments utilizing our proprietary AIDE technology platform that hold the potential to help children and families affected by rare and debilitating diseases such as A-T. Quince’s priority is to advance the Phase 3 clinical trial of EryDex to evaluate its safety and efficacy for the treatment of A-T, then expand our development efforts into other potential indications that leverage our proprietary AIDE technology platform."

Quince is well-capitalized into 2026 and intends to focus its development expertise and financial resources toward advancing a single global Phase 3 NEAT (Neurologic Effects of EryDex on Subjects with A-T) clinical trial, which is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the neurological effects of EryDex on patients with A-T. Enrollment for the Phase 3 NEAT trial is expected to begin in the second quarter of 2024. The company plans to enroll approximately 86 A-T patients aged six to nine years-old and approximately 20 additional A-T patients aged 10 years or older. This pivotal clinical trial will be conducted under a Special Protocol Assessment (SPA) that has been agreed with the U.S. Food & Drug Administration (FDA), which should allow for the submission of a New Drug Application (NDA) following completion of this single study, assuming positive results.

Quince’s integrated senior leadership team holds extensive development, clinical, regulatory, and commercial expertise, and includes:

Dirk Thye, M.D. – Chief Executive Officer and member of Quince’s Board of Directors
Charles Ryan, J.D., Ph.D. – President
Guenter R. Janhofer, M.D., Ph.D. – Chief Medical Officer
Brendan Hannah, M.B.A. – Chief Business Officer and Principal Financial Officer
Giovanni Mambrini, MSc – Chief Technology Officer
Thomas Sabia, M.B.A. – Chief Commercial Officer
Pamela Williamson, RAC, FRAPS, M.B.A. – Head of Regulatory Affairs
EryDel’s former Chief Executive Officer, Luca Benatti, Ph.D., also joins Quince’s Board of Directors.

The acquisition of EryDel was completed with no upfront cash payment, using a stock-for-stock exchange and potential downstream milestone cash payments. EryDel stockholders now own 15.2% of Quince’s outstanding shares and may be issued up to an additional 725,036 shares of the company’s common stock (equal to 16.6% of Quince’s currently outstanding shares – inclusive of the shares issued) upon the first anniversary of the transaction closing. EryDel stockholders also will be entitled to up to $485 million in potential total downstream cash payments, including up to $5 million in development milestones, $25 million at NDA acceptance, $60 million in approval milestones, and $395 million on market and sales milestones, with no royalties paid to EryDel stockholders. The transaction includes the assumption of EryDel’s $13 million (€10 million in principal) European Investment Bank (EIB) loan with scheduled payments beginning in the second half of 2026.