#ASCO21: Gilead Trodelvy new subgroup data shows benefit in earlier-line TNBC patients

 With AstraZeneca and Daiichi sniffing at its trail, Gilead has worked hard to hold an advantage for ADC Trodelvy in particularly hard-to-treat breast cancer patients. Now, the drugmaker is reading out more late-stage data showing some benefit in earlier-line patients, and it could help carve a path forward to a bigger market share.

Gilead’s Trodelvy extended survival in a subgroup analysis of relapsed or refractory triple-negative breast cancer patients in the second line, a positive sign Gilead hopes could spell earlier lines of therapy for its TROP2-directed ADC, according to data from the Phase III ASCENT study set to be presented at this weekend’s #ASCO21.

Trodevly received a full approval from the FDA in April to treat metastatic TNBC patients in the second line or later as well as an accelerated nod in urothelial carcinoma the same month.

In second-line patients who reported disease progression within 12 months of (neo)adjuvant chemo. Trodelvy cut the risk of disease worsening or death by 59% over chemo with a PFS of 5.7 months compared with 1.5 months on chemo. The therapy also posted a median OS of 10.9 months compared with 4.9 months for patients on chemo.

Trodelvy also showed a higher overall response rate compared with chemo — 30% compared with 3% — and a safety profile in the subgroup that was consistent with other studies, Gilead said. There were no treatment-related deaths in the subgroup.

Reading out in earlier lines of therapy will be a major focus point for Gilead as it looks to build its lead over AstraZeneca and Daiichi Sankyo, which are looking for approval for a TROP2-directed ADC of their own.

In early May, the partners read out Phase I cohort data for their next-gen ADC datopotamab deruxtecan showing a 43% response rate and five confirmed complete or partial responses among 21 patients with TNBC. The vast majority of those patients were treated with 6-mg doses of the drug while two received an 8-mg high dose. On top of the five confirmed responses, the partners were awaiting confirmation on four additional responses at the Jan. 8 cutoff date. Datopotamab posted a disease control rate of 95%.

Gilead won a full approval for Trodelvy in TNBC based on the strength of ASCENT, which showed Trodelvy reduced the risk of death in TNBC patients by 49%, with a median OS of 11.8 months, as opposed to the 6.9 months achieved by standard single-agent chemotherapy. PFS came in at a median of 4.8 months, compared to 1.7 months on chemotherapy.

https://endpts.com/asco21-gileads-trodelvy-reads-out-new-subgroup-data-showing-benefit-in-earlier-line-tnbc-patients/

Harpoon Drops After Prostate Cancer Candidate Shows Cytokine-Related Adverse Events

 

• Harpoon Therapeutics Inc HARP 24.09% has announced interim data from the ongoing dose-escalation portion of a Phase 1/2a trial evaluating HPN424 in patients with metastatic castration-resistant prostate cancer (mCRPC).
• Data were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
• HPN424 targets prostate-specific membrane antigen (PSMA) and is based on Harpoon's proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient's immune cells to kill tumor cells.
• As of April 23, the data cutoff date, 89 patients have been dosed across 13 cohorts at fixed doses of 1.3 to 160 ng/kg and in step dosing cohorts up to 300ng/kg administered as a weekly intravenous infusion.
• Antitumor activity included one confirmed partial response, PSA declines, and circulating tumor cell (CTC) reductions.
• Treatment duration of over 24 weeks was observed in 15 of 74 (20%) of patients, including 8 of 17 (47%) chemo-naïve patients.
• CRS and transaminitis events were observed most often in Cycle 1, with diminished frequency and severity in subsequent cycles.
• Dose Limiting Toxicities (DLTs) were observed at doses ranging from 96 to 300ng/kg and did not limit escalation, and Maximum Tolerated Dose was not reached.
• 2/89 patients discontinued treatment due to treatment-related AEs.
• Harpoon's management will host a webcast and conference call today at 4 p.m. ET.

https://www.benzinga.com/general/biotech/21/06/21430510/harpoon-therapeutics-stock-drops-after-prostate-cancer-candidate-shows-cytokine-related-adverse-e

PDS Biotech Expands study of PDS0101 and KEYTRUDA® in Head and Neck Cancer

 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing novel cancer therapies and infectious disease vaccines based on the Company’s proprietary Versamune® T-cell activating technology, today announced the protocol amendment to expand its Phase 2 VERSATILE-002 study to include patients, in an additional arm, who have failed prior checkpoint inhibitor (CPI) therapy (CPI refractory patients). The VERSATILE-002 study is designed to evaluate PDS0101 in combination with KEYTRUDA® (pembrolizumab) in the treatment of advanced human papillomavirus (HPV)-associated head and neck cancer and is currently being run at approximately 20 clinical sites in the US.

VERSATILE-002 was initially opened to checkpoint inhibitor naive HPV16-associated head and neck cancer patients in first line treatment of recurrent or metastatic cancer.   The trial is actively recruiting patients who have the option to receive the two immunotherapies rather than chemotherapy as their first line of treatment for recurrent disease. The additional study arm will evaluate the objective response to the combination among approximately 40 patients with advanced head and neck cancer who have failed multiple treatments, including checkpoint inhibitor therapy. Objective response is measured by radiographic tumor responses according to RECIST 1.1. In the expansion arm, the first 21 patients will be evaluated for safety and objective response before the arm progresses to full enrollment.

The inclusion of CPI re

fractory patients in VERSATILE-002 follows the publication of an abstract and subsequent presentation of interim data in another Phase 2 trial (NCT04287868) being led by the National Cancer Institute (NCI) evaluating the combination of PDS0101 (Versamune®-HPV16) in combination with two investigational immunotherapies. That trial recently reported clinical responses with objective responses (tumor reduction of 30% or more) in 63% (5/8) of HPV16-positive cancer patients who had failed chemotherapy, radiation, and checkpoint inhibitor therapy.

“There is an enormous unmet medical need in advanced head and neck cancer patients who have failed multiple therapies, including chemotherapy, radiation and checkpoint inhibitor therapy. We believe the combination of PDS0101 and KEYTRUDA® has the potential to significantly improve clinical outcomes for these patients who have limited treatment options,” commented Dr. Lauren Wood, Chief Medical Officer of PDS Biotech.

https://www.globenewswire.com/news-release/2021/06/03/2241366/0/en/PDS-Biotechnology-Expands-VERSATILE-002-study-of-PDS0101-and-KEYTRUDA-in-Advanced-Head-and-Neck-Cancer-to-Include-Patients-Who-Have-Failed-Prior-Treatment-with-Checkpoint-Inhibitor.html

FDA Authorizes Lower Dose of REGEN-COV™ (casirivimab and imdevimab) Antibody for Covid-19

 Only antibody therapy currently available in all 50 states, including eight states with high rates of two variants of concern

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced the U.S. Food and Drug Administration (FDA) updated the Emergency Use Authorization (EUA) for REGEN-COV™, lowering the dose to 1,200 mg (600 mg casirivimab and 600 mg imdevimab), which is half the dose originally authorized. As part of the updated EUA, REGEN-COV should be administered by intravenous (IV) infusion; subcutaneous (SC) injections are an alternative when IV infusion is not feasible and would lead to a delay in treatment.

"Despite increased use of vaccines, thousands of patients are still becoming infected in the U.S. every day, with many at high risk of serious complications from COVID-19. Unfortunately, to date only a fraction of patients eligible for antibody treatments have received them, which we hope will change based on this updated FDA authorization. REGEN-COV is readily available and supplied free of charge by the U.S. government," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "REGEN-COV has also demonstrated potency against the main variants of concern to date in vitro and is the only antibody therapy currently available across the U.S., including in states where variants first identified in Brazil and South Africa are circulating at a higher rate."

https://www.prnewswire.com/news-releases/fda-authorizes-lower-1-200-mg-intravenous-and-subcutaneous-dose-of-regen-cov-casirivimab-and-imdevimab-antibody-cocktail-to-treat-patients-with-covid-19--301305941.html

Apple's MagSafe Chargers Could Interfere With Cardiac Implants: American Heart Association

 Apple Inc’s 

AAPL MagSafe devices could interfere with pacemakers if they are held very close to the implant or held over the skin, according to American Heart Association, Appleinsider reported Thursday.

What Happened: The findings were reportedly published in the Journal of the American Heart Association, which agreed with a report by Heart Rhythm Journal, which in turn claimed that when the iPhone 12 is brought in close contact with certain implantable cardiac devices they are affected.

“Our study demonstrates that magnet reversion mode may be triggered when the iPhone 12 Pro Max is placed directly on the skin over an implantable cardiac device and thus has the potential to inhibit [life-saving] therapies, “ the Association’s report noted, as per Appleinsider.

The Association was reported to have used an iPhone 12 Max phone for its tests against a series of 11 different pacemakers and defibrillators.

The medical devices were both “in vivo” — meaning they were implanted in patients or “ex vivo” — meaning they were newly unboxed or not yet implanted devices, as per the Association.

Why It Matters: The “iPhone 12 Pro Max was able to trigger magnetic reversion mode at a distance up to 1.5cm [0.6 inches],” said the report, as per AppleInsider.

"Our study suggests otherwise as magnet response was demonstrated in 3/3 cases in vivo."

The Association noted that people often put their smartphones in breast pockets over a device that can be in close proximity to cardiac implantable electronic devices, which “can lead to asynchronous pacing or disabling of antitachycardic therapies.”

An Apple advisory on MagSafe states, “To avoid any potential interactions with these devices, keep your iPhone and MagSafe accessories a safe distance away from your  device (more than 6 inches / 15 cm apart or more than 12 inches / 30 cm apart if wirelessly charging).”

Apple launched the iPhone 12 lineup in October last year. The phones are 5G capable and come with features like a Lidar scanner along with MagSafe charging and accessories such as wallets.

https://www.benzinga.com/news/21/06/21423782/apples-magsafe-chargers-could-interfere-with-cardiac-implants-warns-american-heart-association

Asco 2021 – Keytruda’s adjuvant kidney win is the real deal

 Those fretting about the magnitude of Keytruda’s disease-free survival win in Keynote-564, the first positive phase 3 trial of an adjuvant immunotherapy in renal cancer, need not have worried. The study’s just unveiled Asco late-breaker has shown a 32% reduction in risk of disease progression versus placebo (p=0.0010), the likely approvable primary endpoint. Just as important is the secondary endpoint of overall survival, which is showing a 46% reduction in risk of death. True, at p=0.0164 this was not statistically significant – but this was a result of a high bar set at this early interim analysis, corresponding to a December 14, 2020 cutoff. In reality, the strong hint is that Keytruda really is helping renal cancer patients live longer when given as adjuvant for a year within 12 weeks of surgery. The results further underscore the Merck & Co drug’s widening lead against its kidney cancer rivals, in particular Opdivo, though it should be stressed that competitor phase 3 adjuvant studies are under way and start reading out next year.

Source: Dr Toni Choueiri & Asco.

https://www.evaluate.com/vantage/articles/news/snippets/asco-2021-keytrudas-adjuvant-kidney-win-real-deal

Malaysia grants conditional approval for Thai-made AstraZeneca vax

Malaysian health authorities said on Friday conditional approval had been granted for AstraZeneca's COVID-19 vaccine manufactured by Siam Bioscience Co in Thailand.

Health Ministry director-general, Noor Hisham Abdullah, said in a statement the vaccine supply received from Thailand is expected to speed up implementation of Malaysia's national vaccination programme.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-Malaysia-grants-conditional-approval-for-Thai-made-AstraZeneca-vaccine-35516221/