On September 16, 2021 Alpha Cancer Technologies Inc. (ACT) a biopharmaceutical company focused on developing and commercializing targeted immuno-oncology and immunology therapies based on its proprietary recombinant human Alpha Fetoprotein (AFP) platform, reported the presentation of new preclinical data from the Company’s investigational therapy, ACT-903 at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting being held virtually September 16-21, 2021 (Press release, Alpha Cancer Technologies, SEP 16, 2021, View Source [SID1234587845]).

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"We are excited by the promise of ACT-903, our novel protein drug conjugate developed though our AFP platform, which we believe has the potential to overcome the shortcomings of traditional immuno-oncology therapies," said Dr. Igor Sherman, CEO of ACT. "Unlike healthy cells, cancer and suppressor cells express AFP receptors, which allows for our conjugates to selectively deliver chemotherapy payloads to these cancer cells while bypassing normal cells, leading to greater efficacy in a broad range of tumor-specific targets, and reduced off-target toxicity. The preclinical findings we have reported with ACT-903 validates our approach and we look forward to advancing this program into the clinic."

The poster titled, "AFP-Maytansine Conjugate – a Novel Targeted Cancer Immunotherapy," highlights preclinical data from an animal study conducted with Southern Research Institute (SRI) evaluating ACT-903, a novel protein drug conjugate using a proprietary version of recombinant human AFP, combined with a proprietary chemical linker and maytansine toxin.

During the study, four novel AFP-maytansine conjugates of differing drug-protein ratios and slightly different linker structures were administered intravenously (IV) to mice bearing human colon carcinoma (COLO-205) xenografts, at doses previously determined to be safe. Seven days after implantation, mice with tumors greater than 150 mm3 were randomized to receive control or one of the four conjugates (10 animals/ group). Animals were treated daily for two weeks with two days of rest after five doses and tumor volume was assessed twice weekly for 60 days following implantation. In a separate study, the biodistribution of an earlier version of AFP-maytansine conjugate in the COLO-205 model was investigated after a single IV dose.

Highlights from the study are below:

Statistically significant reduction in tumor volume was observed in all treatment groups compared to control beginning at Day 17. In one of the conjugate groups, tumor reduction continued following treatment discontinuation with tumor volumes falling below the limit of detection in 9 of 10 animals
100% survival in ACT-903 group at day 60, compared to 0% survival in the control group by day 38
After a single IV dose, biodistribution study of conjugate showed excellent tumor targeting with maytansine and metabolite accumulation and undetectable bone marrow toxicity
No signs of toxicity were observed in treated mice
ACT has identified the ACT-903 conjugate with the strongest efficacy profile and will advance the program into further studies to support a Phase 1 clinical trial.

Poster Details:

Title: AFP-Maytansine Conjugate – a Novel Targeted Cancer Immunotherapy
Abstract Number: 523P
Authors: I. Sherman, R. Boohaker, K. Stinson, P. Griffin, W. Hill

For more information about the Annual Meeting, please visit: View Source

About ACT-903

ACT-903 (AFP+linker+maytansine) is a novel protein drug conjugate using a proprietary version of recombinant human alpha-fetoprotein (AFP), combined with a proprietary chemical linker and maytansine toxin. ACT-903 has been shown to selectively target AFP receptors found on the surface of solid and liquid cancers as well as myeloid derived suppressor cells and deliver the toxic maytansine payload to these cells.

On September 16, 2021 Translational Drug Development (TD2), a leading precision oncology contract research organization (CRO), and Deep Lens reported a strategic partnership that will enhance access to tailored oncology treatments and novel clinical studies for patients receiving care in community oncology practices (Press release, TD2, SEP 16, 2021, View Source [SID1234587862]). The partnership will enable TD2 to offer Deep Lens’ proprietary clinical trial matching solution, VIPER, as well as other research coordination services, to its drug development clients, thereby improving the ability for hospitals, trial coordinators, investigators, and patients to promote, collaborate, participate in and manage oncology clinical trials.

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There has been tremendous growth in precision oncology, or the development of treatments that target the molecular profile of a patient’s tumor. The number of approved novel immunotherapy and targeted agents for different cancer indications has increased dramatically over the past five years, as has the number of clinical trials studying their safety and efficacy1. However, identifying and recruiting eligible patients for precision medicine trials can be challenging. Complex eligibility criteria coupled with very narrow timelines for enrollment can be difficult and labor intensive for study sites and sponsors. The blending of TD2 expertise in precision oncology with the Deep Lens’ clinical trial matching solution platform will improve efficiencies in trial recruitment and enrollment, increase patient access to trials, specifically at community oncology sites, where the majority of patients are diagnosed, and facilitate enhanced access to the right care, for the right patient, at the right time.

The Deep Lens VIPER platform automates the study screening process from time of patient diagnosis to qualified enrollment through the ingestion of genomic data, EMR, pathology, radiology and other patient data. VIPER provides rich data and interactive reporting capabilities to aggregate site and study-level patient data, making it easier for sites to achieve study objectives.

"The highest priority for TD2 is to ensure every patient that participates in a TD2 clinical trial has the opportunity of achieving clinical benefit," said Stephen Gately, President and CEO at TD2. "Working with the Deep Lens platform and coordinators, TD2 can match cutting edge science and molecular testing results with clinical protocol inclusion/exclusion criterion to ensure patients get access to clinical trials where there is an increased likelihood of benefit. We are truly excited that this partnership has the potential to change the way early phase oncology trials are run and enrolled, taking the pressure off the sites to find the next patient and putting the focus on the right patient."

"The drug development process has expanded significantly as our knowledge and understanding of cancer has evolved, and this has resulted in an increase in the number of precision medicine trials studying targeted therapies. While this is a positive step in our battle against cancer, unfortunately, the large majority of these trials fail to enroll enough patients to progress," said Dave Billiter, co-founder and chief executive officer of Deep Lens. "Our approach is to reach more patients by working in the community oncology setting, where the majority of these patients are diagnosed and treated. The partnership with TD2 will allow us to support drug developers to identify and enroll patients into trials for which they are eligible – through our AI-based platform, we can do this right at the time of a patient’s diagnosis. This means more patients have access to life-changing therapies sooner, and drug developers can more effectively test the safety and efficacy of new therapies in more diverse populations."

On September 16, 2021 Exelixis, Inc. (Nasdaq: EXEL) reported results demonstrating efficacy benefits regardless of prior nephrectomy status with CABOMETYX (cabozantinib) in combination with Bristol Myers Squibb’s OPDIVO (nivolumab) versus sunitinib for patients with previously untreated advanced renal cell carcinoma (RCC) (Press release, Exelixis, SEP 16, 2021, View Source [SID1234587798]). The data, from a post-hoc exploratory analysis of the phase 3 CheckMate -9ER pivotal trial, will be presented as an ePoster available on demand beginning at 8:30 a.m. CEST on Thursday, September 16 during the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (abstract 663P).

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"Patients with advanced kidney cancer who do not have a prior nephrectomy typically face an even worse prognosis than those who undergo the surgery," said Camillo Porta, M.D., Full Professor of Medical Oncology at the A. Moro University of Bari, Italy, and presenting author. "It’s critical to gather more data such as this to help us better understand whether recent treatment advancements improve outcomes specifically for these patients. The consistent efficacy benefits demonstrated in the CheckMate -9ER trial regardless of prior nephrectomy status are reassuring as they continue to support the use of CABOMETYX in combination with OPDIVO for a broad range of patients with advanced kidney cancer."

As previously announced, the phase 3 CheckMate -9ER pivotal trial showed that CABOMETYX in combination with OPDIVO improved overall survival (OS) and doubled median progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in patients with previously untreated advanced RCC. In this new exploratory analysis presented at ESMO (Free ESMO Whitepaper) 2021, at a median follow-up of 23.5 months, PFS and ORR benefits were observed regardless of prior nephrectomy status. The magnitudes of PFS and ORR benefits associated with CABOMETYX in combination with OPDIVO were greater in the subgroup of patients with prior nephrectomy versus those without prior nephrectomy. See table below for additional details.

"Building on prior subgroup analyses from CheckMate -9ER, we’re pleased to offer physicians these additional data that provide more insights into how the combination regimen may benefit specific subsets of patients with advanced kidney cancer," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. "Kidney cancer patients who do not have a prior nephrectomy are an especially difficult-to-treat subset of the patient community that is underserved and faces a particularly poor prognosis. We’re encouraged that these findings show that CABOMETYX in combination with OPDIVO is a valuable first-line treatment option that improves outcomes for these patients."

Table

Outcome*

Prior nephrectomy

No prior nephrectomy

C+N**

n=222

SUN***

n=233

C+N

n=101

SUN

n=95

Median PFS per BICRa (95% CIb), months

19.4
(15.6-22.9)

8.9
(7.0-10.4)

11.3
(8.8-16.0)

7.0
(5.5-9.4)

PFS HRc (95% CI)

0.50 (0.39-0.64)

0.62 (0.43-0.89)

Median OS (95% CI), months

NRd
(NEe)

NR
(28.4-NE)

23.8
(21.4-NE)

29.5
(19.4-29.5)

OS HR (95% CI)

0.54 (0.37-0.78)

0.87 (0.57-1.35)

ORR per BICR
(95% CI), %

60.8
(54.1-67.3)

30.5
(24.6-36.8)

41.6
(31.9-51.8)

23.2
(15.1-32.9)

Complete response
per BICR, %

11.3

6.0

5.0

0.0

Duration of response per BICR (95% CI), months

22.0
(18.0-NE; n=135)

13.8
(8.7-NE; n=71)

17.2
(10.7-NE; n=42)

9.9
(4.9-NE; n=22)

* Data based on minimum follow-up of 16 months (median 23.5 months) for OS in ITT patients, acknowledging censoring at later timepoints.

** C+N: CABOMETYX in combination with OPDIVO

*** SUN: sunitinib

a Blinded independent central review

b Confidence interval

c Hazard ratio

d Not reached

e Not estimable

In CheckMate -9ER, CABOMETYX in combination with OPDIVO was generally well tolerated and reflected the known safety profiles of the tyrosine kinase inhibitor and immunotherapy components in previously untreated advanced RCC. The most common adverse reactions reported in at least 20% of patients treated with CABOMETYX in combination with OPDIVO were diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough and upper respiratory tract infection. A safety analysis with extended follow-up reported at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary Cancers Symposium identified no new safety signals; among patients treated with OPDIVO and CABOMETYX, 6.6% discontinued both agents due to treatment-related adverse events, 9.7% discontinued OPDIVO only and 7.2% discontinued CABOMETYX only.

About CheckMate -9ER

CheckMate -9ER is an open-label, randomized (1:1), multi-national phase 3 trial evaluating patients with previously untreated advanced or metastatic RCC with a clear cell component. A total of 651 patients (22% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to CABOMETYX at a dose of 40 mg once-daily and OPDIVO (n=323) versus sunitinib (n=328). The primary endpoint is PFS; secondary endpoints include OS and ORR. The primary efficacy analysis compares the doublet combination regimen of CABOMETYX and OPDIVO versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About RCC

The American Cancer Society’s 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common form of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.1 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.3

About 70% of RCC cases are known as "clear cell" carcinomas, based on histology.4 The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

On September 16, 2021 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) and Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences", HKEX: 1877; SSE: 688180) reported positive interim results from the pivotal study "JUPITER-06" (NCT03829969), a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab in combination with chemotherapy as a first-line therapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) (Press release, Coherus Biosciences, SEP 16, 2021, View Source [SID1234587814]). The study met the co-primary endpoints with statistically significant and clinically meaningful improvements in progression free survival (PFS) and overall survival (OS) for patients treated with the toripalimab and chemotherapy combination compared to chemotherapy alone.

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The results will be summarized by Dr. Feng Wang, Professor at Sun Yat-sen University Cancer Center (SYUCC), Guangzhou, in a mini-oral session during the ESMO (Free ESMO Whitepaper) Congress 2021 on Friday, September 17, 2021 at 12:05 pm Eastern Time. The abstract (#1373MO) is now available on the ESMO (Free ESMO Whitepaper) website.

"The findings of this interim analysis provide strong evidence that the addition of toripalimab to chemotherapy as a first-line treatment for advanced or metastatic ESCC patients has superior PFS and OS than chemotherapy alone," said Dr. Wang. "We look forward to updated analyses of overall survival of the JUPITER-06 study in the future and believe that these results will build a strong argument to support the use of toripalimab in combination with chemotherapy as a new standard first-line treatment in patients with advanced or metastatic ESCC."

"A strong and consistent efficacy and safety profile is emerging for toripalimab across multiple tumor types as data read out from pivotal clinical trials in melanoma, nasopharyngeal carcinoma, urothelial cancer, lung cancer and now also esophageal squamous cell carcinoma," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "We believe toripalimab could be a potential new treatment choice where patients truly need better options. We will collaborate with Coherus to advance a BLA supplement for ESCC to make toripalimab available as quickly as possible for these patients in the U.S."

"With JUPITER-06, toripalimab has once again exhibited compelling efficacy in a first-line setting," said Denny Lanfear, CEO of Coherus. "The significant PFS and similarly robust overall survival data demonstrate that toripalimab in combination with chemotherapy could provide significant clinical benefits to patients with advanced or metastatic esophageal squamous cell carcinoma. We plan to work closely with our partner, Junshi Biosciences, to pursue a BLA supplement for this new indication expeditiously."

About JUPITER-06
A total of 514 treatment-naive advanced or metastatic patients were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin chemotherapy followed by toripalimab or placebo maintenance. The primary endpoints were PFS as assessed by a blinded independent central review (BICR) and overall survival (OS).

At a prespecified interim analysis on March 22, 2021, with median follow-up of 7.4 and 7.3 months in the two arms, there was a significant improvement in OS for the toripalimab-chemotherapy arm compared to the placebo-chemotherapy arm (HR=0.58 [95% CI: 0.43-0.78], P=0.00037) with median OS of 17.0 vs. 11.0 months;

One-year OS rates were 66.0% vs.43.7% for the toripalimab-chemotherapy arm compared to the placebo-chemotherapy arm, respectively;

A significant improvement in PFS assessed by BICR was also detected for the toripalimab-chemotherapy arm compared to the placebo-chemotherapy arm (HR=0.58 [95% CI: 0.46-0.74], P<0.00001);

The OS and PFS benefits were observed across key subgroups, including all PD-L1 expression subgroups;

The incidence of Grade ≥3 adverse events (AEs) (73.2% vs 70.0%) and fatal AEs (8.2% vs 8.2%) were similar between the two arms. No new safety signals were observed.
Junshi Biosciences and Coherus are planning in 2022 to submit a biologics license application supplement to the United States Food and Drug Adminstration for toripalimab for first-line treatment, in combination with platinum-based chemotherapy, of advanced or metastatic ESCC. In China, the supplemental New Drug Application of this indication has been accepted by the National Medical Products Administration (NMPA) in July, 2021.

About Toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 is thought to recharge the immune system’s ability to attack and kill tumor cells. More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China and the United States. Ongoing or completed pivotal clinical trials are evaluating the efficacy and safety of toripalimab for a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). On December 17, 2018, toripalimab was granted a conditional approval from the National Medical Products Administration (NMPA) for the second-line treatment of unresectable or metastatic melanoma. In December 2020, toripalimab was successfully included in the updated National Reimbursement Drug List. In February 2021, the NMPA granted a conditional approval to toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. In April, NMPA granted a conditional approval to toripalimab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. In addition, two supplemental NDAs for toripalimab in combination with chemotherapy for the first-line treatment of patients with advanced, recurrent or metastatic NPC or for the first-line treatment of patients with advanced, or metastatic esophageal squamous cell carcinoma were accepted by the NMPA for review in February and July 2021 respectively.

In the United States, the first toripalimab BLA has been submitted to the FDA for the treatment of recurrent or metastatic NPC. The FDA has granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the 1st line treatment of recurrent or metastatic NPC and also for toripalimab monotherapy in second or third line treatment of recurrent or metastatic NPC. There are currently no PD-1 blocking antibodies approved for use in NPC in the United States. Additionally, FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designations for NPC, mucosal melanoma and soft tissue sarcoma. Earlier in 2021 Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple rare cancers and highly prevalent cancers.

On September 16, 2021 Allarity Therapeutics A/S ("Allarity" or the "Company") reported validation results for its Dovitinib DRP companion diagnostic utilizing data from Novartis’ prior Phase III trial of dovitinib in renal cell carcinoma (RCC), which will be included in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2021 Virtual Congress taking place from September 16 until September 21, 2021 (Press release, Allarity Therapeutics, SEP 16, 2021, View Source [SID1234587830]).

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The poster displays how the RCC patients selected with the Dovitinib DRP companion diagnostic (i.e., those who had a DRP score above 50%) had a median survival of 15.0 months (N=49), compared to a median survival of 11.2 months in the comparator sorafenib arm (N=286, Hazard Ratio: 0.69; 95% Confidence Interval 0.48-0.99) of the clinical trial. When the DRP-Dovitinib score was increased to a score above 67%, the survival in the DRP-selected group increased to a median of 20.6 months (95% Confidence Interval 9.53-35.6, N=15). These results validate that the Dovitinib DRP companion diagnostic can identify RCC patients that benefit from treatment with dovitinib when compared to alternative treatment with sorafenib. The benefit of dovitinib therapy was also evident in progression-free survival data.

Dovitinib, Allarity’s lead clinical-stage asset, is a small molecule, pan-tyrosine kinase inhibitor in-licensed from Novartis. Allarity plans to file a new drug application ("NDA") with the U.S. Food and Drug Administration ("FDA") for the approval of dovitinib for the treatment of RCC during Q4 2021. Allarity has previously filed a pre-market approval (PMA) application for the Dovitinib-DRP. If the FDA provides the anticipated PMA for the Dovitinib-DRP as a companion diagnostic, as well as an NDA approval for dovitinib, Allarity will be able to commercialize dovitinib for DRP-selected RCC patients as an effective new therapy to treat their disease.

Allarity’s CEO Steve Carchedi noted, "The DRP validation data we have been able to publish today further establish the value of our DRP platform in advancing true personalized cancer care, and builds our confidence in a successful road ahead for our planned filing of an NDA for dovitinib. We remain committed to bringing novel oncology therapeutics to market, and to patients, together with their DRP companion diagnostics to improve patient outcomes."