On January 18, 2022 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported that the U.S Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for KIN-3248, a next-generation pan-FGFR inhibitor being developed for intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC)(Press release, Kinnate Biopharma, JAN 18, 2022, View Source [SID1234605539]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The IND clearance for KIN-3248 is another important validation of our Kinnate Discovery Engine and an exciting step forward in our mission to deliver new therapies to patients with difficult-to-treat, genomically-defined cancers," said Nima Farzan, Chief Executive Officer of Kinnate. "By targeting clinically relevant primary FGFR driver alterations and secondary resistance mutations, including FGFR2 and FGFR3 gatekeeper, molecular brake, and activation loop mutations, we believe that KIN-3248 is unique among FGFR inhibitors and has the potential to extend the clinical response of cancer patients with FGFR-altered tumors."

KIN-3248 is an irreversible, small molecule pan-FGFR inhibitor that has been developed to address both primary FGFR2 and FGFR3 oncogenic alterations and those predicted to drive acquired resistance to current FGFR-targeted therapies, including gatekeeper, molecular brake, and activation loop mutations observed in cancers such as ICC and other gastrointestinal cancers. In preclinical studies, KIN-3248 demonstrated inhibitory activity across a wide range of clinically relevant mutations that drive primary disease and acquired resistance.

The Phase 1 trial is expected to initiate in the first half of 2022 and will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-cancer activity of KIN-3248 in FGFR inhibitor naïve and pretreated cancer patients with FGFR2 and/or FGFR3 gene alterations. The dose escalation portion (Part A) of the trial will determine the recommended dose and schedule of KIN-3248 for further evaluation in patients with FGFR2 and/or FGFR3 gene alterations. The dose expansion phase (Part B) of the trial will assess the safety and efficacy of KIN-3248 at the recommended dose and schedule in FGFR inhibitor naïve and pretreated patients with cancers driven by FGFR2 and/or FGFR3 gene alterations, including ICC, UC and other selected adult solid tumors.

Oncogenic FGFR (FGFR1, FGFR2, FGFR3, and FGFR4) gene alterations are observed in approximately 7% of all human cancers. FGFR2 gene fusions and FGFR3 activating alterations are predicted oncogenic drivers in approximately 10-20% of cholangiocarcinoma and 20-35% of urothelial cancers, respectively. While currently approved FGFR inhibitors and those in development provide clinical benefit in these cancer indications, disease progression typically occurs within 6-12 months of starting treatment and is often associated with the emergence of on-target resistance mutations within the FGFR kinase domain.

For more information about Kinnate’s pipeline of targeted oncology therapeutics, please visit: www.kinnate.com/science-and-pipeline.

On January 18, 2022 Incyte (Nasdaq:INCY) reported that it has scheduled its fourth quarter and year-end 2021 financial results conference call and webcast for 8:00 a.m. ET on Tuesday, February 8, 2022 (Press release, Incyte, JAN 18, 2022, View Source [SID1234605538]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The schedule for the press release and conference call/webcast is as follows:

• Q4 & YE 2021 Press Release:

February 8, 2022 at 7:00 a.m. ET

• Q4 & YE 2021 Conference Call:

February 8, 2022 at 8:00 a.m. ET

• Domestic Dial-In Number:

877-407-3042

• International Dial-In Number:

201-389-0864

• Conference ID Number:

13726298

If you are unable to participate, a replay of the conference call will be available for ninety days. The replay dial-in number for the U.S. is 877-660-6853 and the dial-in number for international callers is 201-612-7415. To access the replay you will need the conference ID number 13726298.

The live webcast with slides can be accessed at Investor.Incyte.com and will be available for replay for 90 days.

On January 18, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported interim results (N=63) in its metastatic pancreatic cancer trial (QUILT 88) showing that the overall survival rate for patients doubled compared to historical survival rate of three months after two prior lines of therapy (Manax ASCO (Free ASCO Whitepaper) GI 2019) (Press release, ImmunityBio, JAN 18, 2022, View Source [SID1234605537]). The data of the Phase 2 trial studying a combination immunotherapy (Nant Cancer Vaccine) also show treatment-related serious adverse events were uncommon (8%) and no treatment-related deaths were reported. Based on these findings, ImmunityBio plans to meet with the FDA in 2022 to discuss the path for the approval of combination therapies for pancreatic cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The results were presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal conference, which is being held virtually.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and has one of the highest mortality rates of all major cancers, taking nearly 50,000 lives in the U.S. every year. Surgery and subsequent adjuvant chemotherapy are the preferred treatment options for pancreatic cancer today, but the five-year survival rate for late-stage cases is just 3%. For the majority of patients who present with more advanced disease, treatment typically consists of chemotherapy alone or supportive care for metastatic patients, and chemotherapy with or without radiation for those with locally advanced disease, leaving patients seeking new options.

"There are thousands of patients in advanced stages of this disease and there are few, if any, treatment options for them," said Patrick Soon-Shiong, M.D., Founder and Global Chief Scientific and Medical Officer of ImmunityBio, Inc. "Based on this encouraging data from our QUILT 88 trial, we are hopeful that our Nant Cancer Vaccine can potentially address this unmet need. What’s more, we designed this therapeutic candidate to be administered in an outpatient setting making it more accessible to future patients than traditional immune checkpoint inhibitors."

To date, 27% of third-line or greater patients (17/63) remain on study. The median overall survival in this highly advanced group of patients, who failed two to six prior lines of treatment, is 5.8 months (95% CI: 3.9, 6.9 months) exceeding the approximately three-month historical median overall survival. Of the 63 patients, 30 (48%) had progressed after two prior lines of therapy. Median overall survival in this group was 6.3 months (95% CI: 5.0, 9.8 months), more than doubling the historical overall survival. On the strength of this early data and significant unmet medical need, the company has expanded enrollment in the third-line or greater cohort.

QUILT 88 is an open-label study to evaluate the safety and efficacy of the Nant Cancer Vaccine, comprising ImmunityBio’s IL-15 receptor agonist Anktiva (N-803), its off-the-shelf targeted natural killer cells (PD-L1 t-haNK), and aldoxorubicin, an albumin-modulated agent, plus low-dose chemotherapy. This combination Nant Cancer Vaccine is randomized against standard-of-care high-dose chemotherapy for first- and second-line treatment; the third-line or greater cohort, with an original target of 50 patients, is a single arm with the primary endpoint of overall survival.

QUILT-88 Study Details

This Phase 2, randomized, three-cohort, open-label study will evaluate the comparative efficacy and overall safety of standard-of-care chemotherapy versus low-dose chemotherapy in combination with PD-L1 t-haNK, Anktiva (N-803), and aldoxorubicin in subjects with locally advanced or metastatic pancreatic cancer (NCT04390399). Each treatment setting, as well as each first- and second-line or later maintenance treatment, will be evaluated independently as Cohorts A, B, and C, respectively, with Cohorts A and B having independent experimental and control arms. The study is expected to enroll 328 subjects across all three cohorts giving effect to the expanded enrollment of Cohort C (63 of 80 participants are currently enrolled in Cohort C, third-line or greater). The primary objective of Cohorts A and B is progression-free survival (PFS) per RECIST V1.1, and the objective of Cohort C is overall survival (OS). Secondary objectives include initial safety and additional efficacy measures, including overall response rate (ORR), complete response (CR) rate, durability of response (DoR), disease control rate (DCR), and overall survival (OS).

Currently, three trial sites have been activated: Hoag Memorial Hospital Presbyterian in Orange County, Calif., The Chan Soon-Shiong Institute for Medicine in Los Angeles County, Calif., and Avera McKennan Hospital and University Health Center in Sioux Falls, South Dakota, which serves patients in the tri-state area (Iowa, Nebraska and South Dakota).

On January 18, 2022 Hera BioLabs’ reported that SRG OncoRat is immunodeficient and highly permissive to human prostate cancer xenografts, both patient- and cell line-derived tumors (Press release, Hera BioLabs, JAN 18, 2022, View Source [SID1234605535]). Developed on a Sprague-Dawley background, SRG OncoRats are Rag2/Il2rg double knockouts that lack mature B cells, T cells, and circulating NK cells. Compared to immune-deficient mouse models, the SRG OncoRat provides the following advantages:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Increased tumor take-rates (>90% for MDVR-VCaP cells)
Drug efficacy can be combined with toxicity and metabolism endpoints
Easier surgical procedures including orthotopic tumor implantation
Serial blood and tissue sampling including tumor biopsies for biomarker analysis
Leveraging the superior qualities of the SRG rat (OncoRat), Hera BioLabs has generated a robust platform for evaluating the efficacy of both androgen-dependent and -independent AR blockers. We have generated an enzalutamide (MDV3100)-resistant VCaP prostate cancer cell line (MDVR-VCaP) by passaging VCaP cells under enzalutamide selection. VCaP cells are particularly useful for interrogating AR signaling pathways because they mimic amplification of the AR gene that is commonly seen in men4. Like the parental cell line, MDVR-VCaP cells display robust tumor formation when inoculated into our SRG OncoRat.

Recently published work conducted by Hera highlights the utility of evaluating enzalutamide and castration resistant VCaP xenografts5. In this study, we started by inoculating SRG OncoRats subcutaneously with VCaP or MDVR-VCaP. When tumors reached the size of 1,000-3,000 mm3, rats were castrated and the tumors allowed to progress as CRPC. After a period of tumor regression and re-growth to 2000 mm3, rats were randomized to receive vehicle, enzalutamide, or UT-34 (a selective AR degrader). Figure 1 (adapted from 5) shows percent change in tumor volume for VCaP and MDVR-VCaP tumors following treatment. In SRG rats carrying VCaP tumors, the UT-34 caused significantly more tumor regression than enzalutamide. In rats carrying MDVR-VCaP tumors, enzalutamide did not cause a significant reduction in tumor volume, but UT-34 was highly efficacious and reduced tumors to unmeasurable volumes.

Does your compound circumvent the heartbreaking difficulties of treating castration-resistant or enzalutamide-resistant prostate cancer? Do you need to assess your compound’s efficacy while de-risking your preclinical pipeline? If so, connect with Hera to learn more about how we can assist you.

REFERENCES

Schalken, J. & Fitzpatrick, J. M. Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer. BJU Int 117, 215-225, doi:10.1111/bju.13123 (2016).
Vander Ark, A., Cao, J. & Li, X. Mechanisms and Approaches for Overcoming Enzalutamide Resistance in Prostate Cancer. Front Oncol 8, 180, doi:10.3389/fonc.2018.00180 (2018).
Noto, F. K. et al. The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies. PLoS One 15, e0240169, doi:10.1371/journal.pone.0240169 (2020).
Greene, S. B. et al. Chromosomal Instability Estimation Based on Next Generation Sequencing and Single Cell Genome Wide Copy Number Variation Analysis. PLoS One 11, e0165089, doi:10.1371/journal.pone.0165089 (2016).
Ponnusamy, S. et al. Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer. Cancer Res 77, 6282-6298, doi:10.1158/0008-5472.CAN-17-0976 (2017).

On January 18, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the enrollment of the first patient in the SHIELD (Screening for HIgh-frEquency maLignant Disease) LUNG study, a nearly 10,000-patient prospective, registrational study to evaluate the performance of its next-generation Guardant SHIELD blood test in detecting lung cancer in high-risk individuals ages 50-80 (Press release, Guardant Health, JAN 18, 2022, View Source [SID1234605534]). The study is anticipated to run in approximately 100 centers in the United States and Europe.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Lung cancer is the leading cause of death among both men and women in the U.S. It is also the leading cause of cancer death among men, and the second leading cause of cancer death among women worldwide.1 The U.S. Preventive Services Task Force recommends yearly lung cancer screening using a low-dose computed tomography (CT) scan for people ages 50 to 80 years old who are at high risk for lung cancer because of their smoking history, but who don’t have signs or symptoms.2 Despite these recommendations, only 14% of people eligible for a low-dose CT scan are up to date with screening recommendations.3

"Symptoms of lung cancer don’t appear until the disease is already at an advanced stage. That’s why it’s so important to find lung cancer early, before symptoms start," said Craig Eagle, MD, Guardant Health chief medical officer. "Unfortunately, many people do not follow recommended screening guidelines for lung cancer. We believe a simple blood test could help improve screening rates and detect lung cancer early, when it can most easily be treated."

Eligible participants for the SHIELD LUNG study will include people between the ages of 50 and 80 who are current or former smokers and undergo standard lung cancer screenings using low-dose CT scanning. Enrollment is expected to be complete within 36 months, and if the study is successful, the data will support a pre-market approval (PMA) submission to the U.S. Food and Drug Administration (FDA). Additional information about the SHIELD LUNG study is available on clinicaltrials.gov (NCT05117840).

"The SHIELD LUNG study is the second large-scale screening study initiated by Guardant Health in just over two years to evaluate the performance of our blood tests for early cancer detection. Our unique combination of medical, clinical and operational expertise, in partnership with our clinical investigators and study sites, allows us to move forward rapidly with enrollment for this very important study," said AmirAli Talasaz, Guardant Health co-CEO. "Lung cancer screening is known to save lives. This study will add to the growing body of evidence that supports the use of our blood tests to screen for cancer early. It also reinforces our deep commitment to providing patients with a simple blood test that is accurate and easier than the current standard of care, to catch lung cancer at the earliest stages where there can be better patient outcomes.