#ASCO21: Spectrum Pharma Presents Poziotinib Data in Patients with Brain Metastases

 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, today presented an e-poster on poziotinib CNS activity in patients with NSCLC with EGFR or HER2 exon 20 mutations. These data from Cohorts 1, 2 and 3 of the ongoing ZENITH20 clinical trial assessed the results from 36 patients with brain metastases at baseline with three patients (8%) achieving intracranial complete responses. The presentation titled "CNS activity of poziotinib in NSCLC with exon 20 insertion mutations" is available on the website for the 2021 ASCO Annual Meeting being held June 4-8, 2021.

"CNS metastases are a common and life-threatening complication of metastatic disease in NSCLC patients," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "These data show clinically meaningful CNS activity for poziotinib treated NSCLC patients with CNS metastases with EGFR or HER2 exon 20 insertion mutations."

https://finance.yahoo.com/news/spectrum-pharmaceuticals-presents-poziotinib-data-130000353.html

Pfizer jab produces less antibodies against Delta variant: Lancet

 People fully vaccinated with two doses of the Pfizer-BioNTech vaccine are likely to have more than five times lower levels of neutralising antibodies against the Delta variant (B16172) when compared to the original strain, according to new laboratory data that supports Pfizer's plans to deliver booster shots in Autumn.

This antibody's response was even lower in people who had only received one dose. After a single dose of Pfizer-BioNTech, 79 per cent of people had a quantifiable neutralising antibody response against the original strain, but this fell to 50 per cent for Alpha variant (B117), 32 per cent for Delta variant (B16172) and 25 per cent for Beta variant (B1351), showed the study, published as a Research letter in The Lancet on Thursday.

The results also show that levels of these antibodies are lower with increasing age and that levels decline over time, while no correlation was observed for sex or body mass index.

Although laboratory results such as these are needed to provide a guide as to how the virus might be evolving to escape the first generation of vaccines, levels of antibodies alone do not predict vaccine effectiveness and prospective population studies are also needed. Lower neutralising antibody levels may still be associated with protection against Covid-19, said researchers from the Francis Crick Institute and the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre in the UK.

"This virus will likely be around for some time to come, so we need to remain agile and vigilant. Our study is designed to be responsive to shifts in the pandemic so that we can quickly provide evidence on changing risk and protection," said Emma Wall, UCLH Infectious Diseases consultant.

"The most important thing is to ensure that vaccine protection remains high enough to keep as many people out of hospital as possible. And our results suggest that the best way to do this is to quickly deliver second doses and provide boosters to those whose immunity may not be high enough against these new variants," she added.

The findings also support current plans to reduce the dose gap between vaccines since they found that after just one dose of the Pfizer-BioNTech vaccine, people are less likely to develop antibody levels against the Delta variant as high as those seen against the previously dominant Alpha (B117) variant.

For the study, the team analysed antibodies in the blood of 250 healthy people who received either one or two doses of the Pfizer-BioNTech Covid-19 vaccine, up to three months after their first dose.

The researchers tested the ability of antibodies to block entry of the virus into cells, so called 'neutralising antibodies', against the original strain first discovered in Wuhan, China; the dominant strain in Europe during the first wave in April 2020 (D614G); and the Alpha, Beta and Delta variants.

The study will be extended to participants vaccinated with the Oxford/AstraZeneca vaccine.

Researchers have submitted their findings to the Genotype-to-Phenotype National Virology Consortium (G2P-UK), the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) and the Joint Committee on Vaccination and Immunisation (JCVI), as evidence of the level of protection people might receive against the new variants after one dose and both doses of the Pfizer Covid-19 vaccine.

https://www.business-standard.com/article/current-affairs/pfizer-jab-produces-less-antibodies-against-delta-variant-lancet-121060400516_1.html

Why Cullinan Oncology Is Soaring

 Shares of Cullinan Oncology (NASDAQ:CGEM) were skyrocketing 19.5% higher as of 11:21 a.m. EDT on Friday. The big jump came after the company announced additional data for its ongoing phase 1/2a study evaluating CLN-081 in treating non-small cell lung cancer (NSCLC).

Cullinan stated that objective partial response (significant tumor shrinkage) was observed in 21 of the 42 evaluable patients in the phase 1/2a study of CLN-081 across all dose levels. The company said that 76% of all patients showed at least some tumor regression at six weeks.

CLN-081 also appeared to have a relatively good safety profile. Cullinan said that no patients experienced any treatment-related rash of grade 3 (severe) or higher. All adverse events were "manageable with conventional supportive care," according to the company.

Investors were clearly happy with both the efficacy and safety data released by Cullinan. The company's management team was upbeat as well, with CEO Owen Hughes stating, "We remain encouraged with CLN-081's emerging profile."

Cullinan's data is being featured in an on-demand poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting. The biotech stock could have other catalysts on the way. Cullinan hopes to soon file for approvals to initiate clinical studies of experimental drugs CLN-619 and CLN-049. 

https://www.fool.com/investing/2021/06/04/why-cullinan-oncology-stock-is-skyrocketing-today/

#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