On September 22, 2021 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported an update on its development programs in oncology and infectious disease for mupadolimab (formerly CPI-006), a humanized monoclonal antibody directed against CD73 with a proposed dual mechanism of activating B cells to generate immune responses to viruses and tumor antigens, and inhibiting the production of immunosuppressive adenosine in the tumor micro environment (Press release, Corvus Pharmaceuticals, SEP 22, 2021, View Source [SID1234590167]).

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Corvus is developing mupadolimab as a therapeutic for oncology indications and for infectious disease, starting with COVID-19. Today the Company announced results from its Phase 3 clinical trial of mupadolimab for COVID-19, which have been published online at medRxiv.org. The results, which cover 40 patients that were enrolled in the trial prior to its voluntary discontinuation, suggest improvement in the primary and key secondary endpoints in patients treated with single doses of mupadolimab at 2mg/kg and 1mg/kg compared to placebo. No drug related adverse events were reported in the trial.

"We believe the results from our Phase 3 Covid trial show the potential for a dose response effect on the primary endpoint of time to respiratory failure or death for the 2mg/kg and 1mg/kg mupadolimab cohorts compared to placebo. Secondary endpoints also favored the cohorts receiving mupadolimab. Most interestingly, antiviral responses in the 2mg/kg cohort trended higher across all variants tested, including delta. Cross reactivity to the delta variant is of interest as patients were enrolled prior to its emergence as the dominant variant in the United States," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "As expected when we discontinued the trial, statistical significance was not reached due to the sample size. However, we are very encouraged by the consistent trends and immune response data, which we believe support mupadolimab’s proposed mechanism of action and its potential value for the treatment of viral infections. Combined with the findings in our previous Phase 1 trial in 29 patients, we believe there is mounting evidence that mupadolimab could become a universal treatment for viral diseases, with the ability to address immune escape from variants. We plan to evaluate our next steps with mupadolimab for COVID-19 as we continue to analyze the trial data and explore partnership opportunities to continue its development as a therapeutic."

Mupadolimab also is currently being studied in a Phase 1b/2 clinical study in patients with HPV+ oropharyngeal cancers and non small cell lung cancers (NSCLC) that have failed previous treatment with anti-PD-1 therapy and chemotherapy. Data from the Phase 1b/2 clinical study has been accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November.

"Mupadolimab is one of the most studied anti-CD73 antibodies and is uniquely positioned with a potential dual mechanism, B cell activation and inhibition of immunosuppressive adenosine production," said Dr. Miller. "The complementary mechanisms could result in enhanced immune responses to viral antigens and to tumor antigens. We believe this will enable a unique approach to treating cancers, that can benefit both from removing the adenosine-mediated blockade of the immune system and enhancing immune responses through B cell activation. We look forward to presenting new data from our Phase 1b/2 oncology study at the SITC (Free SITC Whitepaper) meeting in November."

Mupadolimab for COVID-19 Trial Results
This was a randomized, double blind placebo-controlled trial design. In July, Corvus discontinued the clinical trial, which had planned to enroll approximately 1,000 patients, due to positive trends exhibited by COVID-19 vaccines in lowering serious infection and hospitalizations at that time. The discontinuation was not related to any safety or efficacy issues observed in study patients and occurred prior to the recent surge in COVID-19 cases and before the dominant emergence of the delta variant. Of the 40 patients enrolled prior to the discontinuation, 15 received the mupadolimab 2mg/kg dose, 14 received the mupadolimab 1mg/kg dose, and 11 received placebo. Treatment arms were well balanced, except for the 2mg/kg cohort, which had patients with more severe disease on admission with 60% on non-invasive ventilation or high flow oxygen devices, compared to 7% in the 1mg/kg cohort and 27% in the placebo cohort. Data from the three cohorts remained blinded until the final analysis.

The primary endpoint of the clinical trial was the proportion of patients progressing to respiratory failure or death during the 28 days after dosing. In the 2mg/kg cohort, 93.3% of patients were alive and free from respiratory failure, compared to 85.7% in the 1mg/kg cohort and 81.1% in the placebo. The results in the placebo control group were in line with results reported in other randomized trials. In addition, positive trends favoring mupadolimab treatment compared to placebo were seen for all the key secondary endpoints, including time to clinical improvement, time to sustained clinical improvement and time to hospital discharge.

MUPADOLIMAB 2MG/KG AND 1MG/KG VS. PLACEBO
(all received standard of care treatment)

2 MG/KG + SOC
(N=15) 1 MG/KG + SOC
(N=14) PLACEBO + SOC
(N=11)
PRIMARY ENDPOINT:
Free from Respiratory Failure or Death (%) 93.3 85.7 81.1
SECONDARY ENDPOINTS:
Median Days to Improvement (95% CI) 7.0 (4-9) 5.5 (3-14) 11.0 (2-14)
Median Days Sustained Improve (95% CI) 8.0 (4-12) 6.0 (3-14) 11.0 (2-21)
Median Days to Discharge (95% CI) 6.0 (4-12) 4.0 (2-5) 7.0 (2-12)

The results also included anti-viral antibody responses for 26 patients for which pre-treatment and day 28 blood serum are available (8 from the 1mg/kg cohort, 11 from the 2mg/kg cohort and 7 from the placebo cohort). Serum titers in the 2mg/kg cohort appeared to trend higher against the original COVID-19 strain and variants (alpha (B.1.1.7), beta (B.1.351), gamma (P.1) and delta (B.1.617.2), with several patients exhibiting very high titers. Patients in the 2mg/kg cohort demonstrated higher cross-reactivity with the beta, gamma and delta variants compared to 1mg/kg and placebo.

On September 22, 2021 Specialised Therapeutics reported that SINGAPORE patients with an aggressive form of lung cancer (metastatic small cell lung cancer) can now access a new therapy that may improve outcomes (Press release, Specialised Therapeutics Asia, SEP 22, 2021, View Source [SID1234590165]).

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The drug ZEPZELCA (lurbinectedin) has been provisionally approved by Singapore’s Health Sciences Authority (HSA) "for the treatment of adult patients with metastatic small cell lung cancer (SCLC) who have progressed after prior platinum-containing chemotherapy".[1]

This means patients who have failed other existing treatment options will now have a further therapeutic option.

ZEPZELCA is the first new therapy approved by the HSA to treat second-line SCLC in more than two decades, and is the third oncology drug in Specialised Therapeutics (ST) portfolio to receive HSA approval.

The Singapore approval follows on from approvals by the US Food and Drug Administration (FDA) decision[2], as well as the Therapeutic Goods Administration (TGA) in Australia.[3]

Lung Cancer Oncologist and past president of Australasian Lung Cancer Trials Group Professor Paul Mitchell from the Olivia Newton-John Cancer and Wellness and Research Centre said SCLC was particularly aggressive and more than two-thirds of patients were diagnosed with extensive stage disease. He said fewer than 5% of these patients currently survived more than five years post diagnosis.[4,5]

"The new availability of ZEPZELCA will be welcomed by patients, families and the medical community, as we strive to improve patient outcomes for this disease," Professor Mitchell said.

"With this approval, we now have another option for patients who have progressed after prior platinum-based treatments. This provides an opportunity for them to continue treatment and potentially, improve outcomes."

The HSA approval of ZEPZELCA has been granted following collaboration with the US FDA via the ‘Project Orbis’ initiative, due to the high unmet clinical need in SCLC. It is based on monotherapy clinical data from an open-label, multi-centre, single-arm study in 105 adult platinum-sensitive and platinum-resistant patients with SCLC who had disease progression after treatment with platinum-based chemotherapy.[6]

The data, which appeared in The Lancet Oncology May 2020 issue, demonstrated that in patients with relapsed SCLC, ZEPZELCA provided an ORR of 35% and a median duration of response of 5.3 months as measured by investigator assessment (30% and 5.1 months respectively, as measured by an independent review committee (IRC)).[6]

The provisional approval is the subject of a further confirmatory study in more than 700 patients with 2L SCLC. This study is expected to be completed in 2025.

ZEPZELCA is being made available in Singapore by independent pharmaceutical company Specialised Therapeutics under exclusive license from its international partner PharmaMar.

Specialised Therapeutics Chief Executive Officer Mr Carlo Montagner said lung cancer was the third most common cancer in Singapore, representing more than 22% of all cancer deaths. SCLC represented between 10 – 15% per cent of all lung cancer diagnoses.[7,8]

"We are delighted to be able to provide a new therapy option in Singapore for patients with this difficult to treat cancer," he said.

"While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment.

"We expect that this therapy may now be an option for up to 100 Singapore patients every year and look forward to making a difference for these patients and their families."

PharmaMar president José María Fernández Sousa-Faro, PhD, said the company was delighted South-East Asian patients would now be provided access to ZEPZELCA.

"We are pleased to bring a new treatment choice to relapsed SCLC patients. "The accelerated approval of ZEPZELCA underscores its potential to fill an unmet need in this often-overlooked SCLC community."

ZEPZELCA has been available in Singapore via an Early Access Program since July 2020.

About SCLC in Singapore

SCLC represents a serious condition. It is a particularly aggressive type of lung cancer related to smoking that represents approximately 10-15% of all lung cancers, accounting for more than 275,000 new cases worldwide every year.[9,10] SCLC is characterised by rapid growth, early dissemination that is often asymptomatic and with acquired resistance to drugs. SCLC is staged into limited-stage or extensive-stage disease. Limited-stage disease is potentially curable with aggressive therapy consisting of concurrent chemoradiotherapy, prophylactic cranial irradiation, and occasionally, surgery.[11,12] However, nearly two-thirds of SCLC patients have extensive-stage disease at diagnosis, which is not curable, and patients are treated with palliative intent, with a median survival of 7 to 11 months after diagnosis and with less than 5% survival at 2 years.[13,14]

Lung cancer is the third most common cancer in Singapore and represents 22.3% of all cancer deaths. Between 2014 and 2018, approximately 7,945 new cases of lung cancer were diagnosed in Singapore, with 10-15% of these classified as SCLC (between 150 and 240 new SCLC cases annually).[7,8] While the age-standardised incidence rate of all lung cancer has been in decline since the 1970’s (mid-50’s per 100,000 in 1968 to mid-30’s per 100,000 in 2017), the five-year relative survival has seen a moderate increase to approximately 10% in 2017. Globally, the prognosis of patients with SCLC is dismal with a 5-year survival rate of less than 5% and an average overall survival period of only 2-4 months for patients not receiving any active treatment.[11,12]

Modern studies, including those of recent immunotherapies, suggest that between 40-60% of patients that receive front-line therapy will be clinically eligible for second-line therapy.[15-18] This suggests that, based on 2014-2018 lung cancer incidence figures from the Singapore Cancer registry[8], between 60 to 100 patients would be eligible for second-line SCLC treatment in Singapore.

About ZEPZELCA (lurbinectedin)
ZEPZELCA is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death.[1]

ZEPZELCA or injection 4 mg is a prescription medicine used to treat adults with a kind of lung cancer called small cell lung cancer (SCLC) that has spread to other parts of the body (metastatic) and who have received treatment with chemotherapy that contains platinum, and it did not work or is no longer working. ZEPZELCA is approved based on response rate and how long the response lasted. Additional studies will further evaluate the benefit of ZEPZELCA for this use.

About the Phase II Monotherapy Trial
The Phase 2 trial of ZEPZELCA was an open-label, single-arm study, which enrolled a total of 105 SCLC patients at 26 hospitals in six European countries and the U.S.[6] In the trial, platinum-sensitive and platinum-resistant patients were treated with ZEPZELCA 3.2 mg/m2, administered as a 60-minute IV infusion repeated every 21 days until disease progression or unacceptable toxicity. The primary endpoint, ORR, was 35% and the median duration of response was 5.3 months as measured by investigator assessment (30% and 5.1 months respectively, as measured by an IRC).[6] ZEPZELCA was discontinued in 1.9% of patients and was delayed in 30.5% of patients due to an adverse reaction. Dose reductions for an adverse reaction occurred in 25% of patients.[6]

On September 22, 2021 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, reported that Amit Hasija, Chief Financial Officer and Executive Vice President of Corporate Development, will present at the 2021 Cantor Fitzgerald Virtual Global Healthcare Conference on Wednesday, September 29, 2021 at 10:00 a.m. ET (Press release, Milestone Pharmaceuticals, SEP 22, 2021, View Source [SID1234590164]). The conference will be held in a virtual meeting format.

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A live webcast of the presentation can be accessed in the News & Events section of Milestone’s website at www.milestonepharma.com. An archived replay of the webcast will be available on the same website following the presentation.

On September 22, 2021 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company developing novel cancer therapies for patients who are failing, or are resistant to, current treatment regimens reported topline data results from the newly-diagnosed adjuvant arm of its open-label, Phase 2 clinical study being conducted at the MD Anderson Cancer Center (MD Anderson) in Houston, Texas (Press release, Kintara Therapeutics, SEP 22, 2021, View Source [SID1234590163]).

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The Phase 2 trial was a two-arm, biomarker-driven study testing VAL-083 in glioblastoma multiforme (GBM) patients who have an unmethylated promoter of the methylguanine DNA-methyltransferase (MGMT) gene. The Company previously announced (July 2021) topline data results from the recurrent GBM arm of the study which provided important safety and efficacy data to support the continued evaluation of VAL-083 as a treatment option for GBM.

The newly-diagnosed adjuvant arm of the study addressed GBM patients requiring adjuvant therapy after chemoradiation with temozolomide. The trial arm enrolled 39 patients (36 efficacy evaluable) initially receiving a dose of 30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle.

Summary of results:

Progression Free Survival (PFS) for the 36 efficacy evaluable patients is 10.0 months (95% Confidence Interval (CI) 8.2-10.8 months). While this is not a head-to-head trial, historical data for this patient population has demonstrated PFS of 5.3-6.9 months*.
Median overall survival (mOS) for the 36 efficacy evaluable patients is 16.5 months (CI 13.3-19.3 months). While this is not a head-to-head trial historical data for this patient subpopulation has demonstrated mOS of 12.7-16.0 months*.
Consistent with prior studies, myelosuppression was the most common adverse event. One patient experienced a serious adverse event (SAE) possibly related to VAL-083.
The dosing regimen (30 mg/m2/day) of the MD Anderson study mirrors the trial design of the newly-diagnosed adjuvant study arm of the GBM AGILE study. GBM AGILE, which is sponsored by the Global Coalition for Adaptive Research (GCAR), is a revolutionary, patient-centered, registrational, seamless Phase 2/3 adaptive platform trial evaluating multiple therapies for patients with newly-diagnosed and recurrent GBM. VAL-083 currently represents the only therapeutic agent being evaluated in all three GBM patient subtypes: methylated MGMT, newly-diagnosed unmethylated MGMT, and recurrent.

"On behalf of the entire Kintara team, I wish to extend gratitude to MD Anderson, and all of the patients who participated in both arms of the trial," said Saiid Zarrabian, Kintara’s Chief Executive Officer. "The topline results from the newly-diagnosed adjuvant arm are a particularly important milestone for the company as it further affirms the efficacy and safety data reported this past July from the recurrent arm, thus providing additional support and momentum to continue the evaluation of VAL-083 for the treatment of GBM."

Dr. Barbara O’Brien, the Principal Investigator for the Phase 2 study at MD Anderson added, "I continue to be impressed by the clinical data generated by both arms of the study and remain excited by VAL-083’s potential to be a game-changing therapeutic agent to help patients suffering from this deadly disease."

VAL-083 is independent of the MGMT resistance mechanism and has been assessed in over 40 Phase 1 and Phase 2 clinical trials in multiple indications sponsored by the U.S. National Cancer Institute (NCI). Published pre-clinical and clinical data indicate that VAL-083 has activity against a range of tumor types, including lung, brain, cervical, ovarian tumors and hematologic (blood) cancers. VAL-083 has been granted Orphan Drug Designation for GBM by the FDA and EMA and has also been granted Orphan Drug Designations for medulloblastoma and ovarian cancer by the FDA. In addition, the FDA has granted Fast Track Designation for VAL-083 in recurrent GBM. VAL-083 is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer. VAL-083 has not been approved for any indications outside of China.

On September 22, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported that it will present a company overview and business update at the 2021 Cantor Virtual Global Healthcare Conference on Wednesday, September 29, 2021 at 4:00 p.m. Eastern Time (Press release, MEI Pharma, SEP 22, 2021, View Source [SID1234590162]).

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The presentation can be accessed via the Events & Presentations page of the Investors section of MEI Pharma’s website at View Source An archived replay of the webcast will be available on MEI Pharma’s website for at least 30 days after the live event concludes.