On September 22, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported preliminary safety and efficacy data from an investigator-initiated Phase 1/2a trial of oral rigosertib plus the immune checkpoint inhibitor nivolumab in advanced KRAS mutated (KRAS+) non-small cell lung cancer (NSCLC) (Press release, Onconova, SEP 22, 2021, View Source [SID1234590169]). The data, which are being featured in a presentation at the 3rd Annual RAS Targeted Drug Development Summit, support the potential anti-cancer activity of rigosertib-nivolumab combination therapy in this indication and show that the doublet has been well tolerated to-date. Three quarters of patients enrolled in the trial have failed two or more lines of prior therapy and all have failed immune checkpoint inhibitors in various combinations.

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Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, "The data being presented today support the potential applicability of rigosertib’s mechanism of action against multiple KRAS mutations and its synergy with immuno-oncology therapeutics. Radiographic responses were seen across multiple KRAS variants, which potentially differentiates rigosertib from other RAS pathway modulators that target particular KRAS mutations. These responses were observed at the primary tumor site as well as metastatic sites such as the pleura and bone. These results also suggest that rigosertib may augment the response to checkpoint inhibitors, which is consistent with observations from preclinical studies, with potential applicability to indications such as NSCLC, melanoma, and others. Looking forward, we will continue to leverage our investigator-initiated study program to advance rigosertib’s clinical development in high-need KRAS mutated indications while keeping our primary focus on our lead ON 123300 (narazaciclib) program."

Key data from the presentation include:

Demographics:

All enrolled patients (12/12) failed at least one line of prior therapy with a PD-1 checkpoint inhibitor (includes evaluable and non-evaluable patients)
9 of 12 (75%) enrolled patients failed at least two prior lines of therapy
Response Results:

2 of 7 (29%) evaluable patients achieved a partial response (PR)
PRs were observed in patients with two distinct KRAS mutations (G12C, G12V)
3 of 7 (43%) evaluable patients achieved disease control (PR or stable disease)
4 of 7 (57%) evaluable patients experienced progressive disease
Adverse Event Results:

The combination of rigosertib and nivolumab has been well tolerated and the maximum tolerated dose has not been reached to-date. Treatment related adverse events were mostly mild with two grade 3 adverse events.
3 patients discontinued study drug (2 grade 2 genitourinary toxicities, 1 dose limiting grade 3 hyponatremia)
No unexpected safety events or synergistic toxicities have been observed
"Combining rigosertib with the immune checkpoint inhibitor nivolumab has been well tolerated and notably led to partial responses in 29% of evaluable patients who had previously progressed on prior checkpoint inhibitor therapies," said Rajwanth Veluswamy, M.D., Assistant Professor, Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai and Principal Investigator of the trial. "This safety and early efficacy signal highlights the combination of rigosertib and nivolumab’s ability to target KRAS mutated NSCLCs and potentially overcome immune checkpoint inhibitor resistance mechanisms. Importantly, responses were seen with different KRAS+ variants, addressing a critical unmet need."

Mark S. Gelder, M.D., Chief Medical Officer of Onconova, commented, "We look forward to the continuation of this study and to continue development of the rigosertib nivolumab combination as a potential treatment for patients with limited therapeutic options."

Slides from the presentation titled, "Phase 1/2 Trial of Rigosertib & Nivolumab in KRAS-Mutated NSCLC in 2nd+ Line" will be available on the "Scientific Presentations" section of the Onconova website following the conference.

Webinar Featuring Expert Overview from Key Opinion Leaders
Onconova will host a webinar today, September 22, 2021, at 4:30 p.m. ET to discuss the preliminary Phase 1/2a data. The call will feature expert discussion with Dr. Veluswamy and Scott Antonia, M.D., Ph.D., Professor of Medicine at the Duke Cancer Institute and Director of its Center for Cancer Immunotherapy. A question and answer session with these experts will follow formal presentations by Dr. Veluswamy and members of the Onconova management team.

To attend the webinar, click here. A replay of the webinar will be available by visiting the investors and media page on Onconova’s website at www.onconova.com and clicking on the webcast link.

About the Investigator-initiated Phase 1/2a Trial
This Phase 1/2a trial is designed to evaluate the combination of rigosertib and nivolumab in advanced KRAS+ metastatic NSCLC patients who have progressed on standard of care with anti-PD-1 monotherapy or anti-PD-1 in combination with chemotherapy. It includes a dose-escalating Phase 1 portion followed by a Phase 2a dose-expansion portion. Patients in the trial receive oral rigosertib twice daily on days 1-21, and intravenous nivolumab on days 1 and 15 of 28-day cycles. The primary endpoints of the trial are safety assessments to determine maximum tolerated dose and overall response rate. Secondary endpoints include progression free survival and overall survival. For more information on the trial, see ClinicalTrials.gov Identifier: NCT04263090.

On September 22, 2021 XOMA Corporation (NASDAQ: XOMA)’s Chief Executive Officer, Jim Neal, reported that it will present at the 2021 Cantor Fitzgerald Virtual Global Healthcare Conference on Tuesday, September 28, 2021, at 10:20 AM PT (Press release, Xoma, SEP 22, 2021, View Source [SID1234590168]).

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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.