On January 30, 2023 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that the U.S. Food and Drug Administration (FDA) has approved its Guardant360 CDx liquid biopsy test as a companion diagnostic to identify advanced or metastatic breast cancer patients with ESR1 mutations who may benefit from treatment with ORSERDU (elacestrant), a nonsteroidal selective estrogen receptor degrader to be commercialized by Stemline Therapeutics, Inc., a wholly-owned subsidiary of Menarini Group (Press release, Guardant Health, JAN 30, 2023, View Source;advanced-or-metastatic-breast-cancer/default.aspx [SID1234626636]).

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!

Breast cancer is the second leading cause of cancer death in women. The American Cancer Society estimates that about 297,790 new cases of invasive breast cancer will be diagnosed in women in 2023, and about 43,700 women will die from breast cancer.2 ORSERDU is the first therapy to be approved by the FDA for advanced breast cancer patients with ESR1 mutations, with disease progression following at least one line of endocrine therapy. ESR1 mutations are present in approximately 40% of ER+/HER2- advanced breast cancers.

"This FDA approval is great news for breast cancer patients with ESR1 mutations, who now have, for the first time, an approved treatment for their specific type of cancer and a blood-based companion diagnostic," said Helmy Eltoukhy, Guardant Health co-CEO. "We are pleased that the Guardant360 CDx liquid biopsy is now approved so that oncologists and their patients can access comprehensive genomic profiling to see if they are eligible to receive this therapy."

The FDA approved Guardant360 CDx as a companion diagnostic (CDx) in conjunction with the approval of ORSERDU for postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated, advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

"We are proud to bring the very first treatment targeting ESR1 mutations which are present in up to 40% of ER+/HER2- advanced breast cancers," commented Elcin Barker Ergun, CEO of Menarini Group. "We’re also pleased with the approval of the Guardant360 CDx blood test as the companion diagnostic to help oncologists identify patients who may benefit from this innovative endocrine therapy."

The approval as a companion diagnostic for ORSERDU is Guardant Health’s fifth FDA approval for the Guardant360 CDx test and its first in breast cancer.

About ORSERDU (elacestrant)

ORSERDU is approved under the FDA’s Priority Review designation based on the results of the registrational Phase III trial EMERALD, that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients whose tumors harbor an ESR1-mutation. In the group with patients whose tumors had an ESR1 mutation, median PFS was doubled (3.8 vs 1.9 months), and a 45% reduction of death or progression was achieved over SOC. Safety data is consistent with the other endocrine therapies. Most of the adverse events (AEs), including nausea and musculoskeletal pain were grade 1 and 2. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia. For more information about ORSERDU, please visit www.orserdu.com.

About Guardant360 CDx

For oncologists, the FDA-approved Guardant360 CDx test provides comprehensive genomic results from a simple blood draw in seven days, helping them move beyond the limitations of tissue biopsies to rapidly obtain clinically relevant information in time to match patients to the optimal personalized treatment. Guardant360 CDx covers all genes recommended by the National Comprehensive Cancer Network, including those most relevant to clinical care and NSCLC treatment guidelines.

The first FDA-approved blood test for complete genomic testing, Guardant360 CDx is approved as a companion diagnostic to identify patients with non-small cell lung cancer who may benefit from treatment with TAGRISSO (osimertinib), RYBREVANT (amivantamab-vmjw), ENHERTU (fam-trastuzumab deruxtecan-nxki) or LUMAKRAS (sotorasib). It is also FDA approved to identify advanced breast cancer patients with ESR1 mutations who may benefit from treatment with ORSERDU (elacestrant). For more information, visit guardant360cdx.com.

Since being introduced, the Guardant360 test has become widely accepted for blood-based comprehensive genomic profiling with more than 350 peer-reviewed publications. It has been trusted by more than 12,000 oncologists, with more than 250,000 tests performed to date, and is broadly covered by Medicare and many private payers, representing over 230 million lives.

On January 30, 2023 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that it will participate at the BTIG MedTech, Digital Health, Life Sciences, & Diagnostics Tools Conference in Snowbird, Utah on February 14 to 16 (Press release, Delcath Systems, JAN 30, 2023, View Source [SID1234626635]).

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!

Delcath CEO, Gerard Michel will be conducting one-on-one meetings. To request a one-on-one meeting please contact your BTIG representative with interest.

On January 30, 2023 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported that the first patient has been dosed in its Phase 1/2 clinical trial of CFT1946, an orally bioavailable mutant-selective BiDAC degrader for the treatment of BRAF V600 mutant solid tumors (Press release, C4 Therapeutics, JAN 30, 2023, View Source [SID1234626634]).

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!

"Dosing the first patient in the CFT1946 Phase 1/2 clinical trial marks the first degrader to enter clinical development to target BRAF-driven cancers. Many of these patients are typically treated with BRAF inhibitors and have few treatment options once resistance emerges," said Adam Crystal, M.D., Ph.D., chief medical officer of C4 Therapeutics. "Preclinically, in in vivo models, CFT1946 has demonstrated deeper and more durable activity than approved BRAF inhibitors, and promising activity in the setting of resistance to BRAF inhibitors. We look forward to advancing CFT1946 for patients with BRAF V600 mutant cancers including non-small cell lung cancer, colorectal cancer, and melanoma."

The Phase 1/2 clinical trial will primarily investigate safety, tolerability, and anti-tumor activity, with secondary and exploratory objectives to characterize the pharmacokinetic and pharmacodynamic profile of CFT1946. The initial arm of the Phase 1 portion of the study will evaluate CFT1946 as a single agent in patients with BRAF V600 mutant solid tumors. As the Phase 1 trial progresses, an additional arm of the trial will evaluate CFT1946 in combination with trametinib, also in patients with BRAF V600 mutant solid tumors. Following the identification of the recommended dose(s), the Phase 2 portion of the trial is expected to expand to three investigational arms to evaluate: (1) CFT1946 monotherapy in patients with V600 mutant melanoma or non-small cell lung cancer (NSCLC) after prior BRAF inhibitor treatment; (2) CFT1946 in combination with trametinib in patients with V600 mutant melanoma or NSCLC after prior BRAF inhibitor treatment; and (3) CFT1946 in combination with trametinib in patients with V600 mutant NSCLC who have not previously been treated with a BRAF inhibitor.

CFT1946 is C4T’s third oncology program to enter clinical studies from its proprietary TORPEDO platform.

On January 30, 2023 Kite, a Gilead Company (NASDAQ: GILD), and Arcellx, Inc. (NASDAQ: ACLX), reported the closing of the companies’ previously reported global strategic collaboration to co-develop and co-commercialize Arcellx’s lead late-stage product candidate, CART-ddBCMA, for the treatment of patients with relapsed or refractory multiple myeloma (Press release, Arcellx, JAN 30, 2023, View Source [SID1234626633]). Multiple myeloma is an incurable disease for most patients and the need remains for effective, safe and broadly accessible therapies.

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!

Currently being investigated in a Phase 2 pivotal trial, CART-ddBCMA is Arcellx’s T-cell therapy utilizing the company’s novel synthetic binder, the D-Domain. Kite and Arcellx will jointly advance and commercialize the CART-ddBMCA asset in the U.S., and Kite will commercialize the product outside the U.S.

On January 30, 2023 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS) reported the 120 mg monotherapy dosing of patients in the APTIVATE Phase 1/2 clinical trial of tuspetinib (formerly HM43239), an oral, mutation agnostic tyrosine kinase inhibitor (TKI) being developed for the treatment of patients with relapsed or refractory acute myeloid leukemia (R/R AML) (Press release, Aptose Biosciences, JAN 30, 2023, View Source [SID1234626632]). In parallel, another clinical response has been achieved by a R/R AML patient receiving 40 mg tuspetinib once daily orally in the original dose exploration trial, the second response at the recently launched low-dose 40 mg cohort.

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!

Tuspetinib, a once daily oral agent designed to simultaneously target SYK, JAK1/2, FLT3, and other kinases operative in AML, has thus far as a monotherapy safely delivered multiple complete remissions and clinical responses across four dose levels (40mg, 80mg, 120mg, and 160mg) in AML patients that previously had been failed by chemotherapy, BCL2 inhibitors, hypomethylating agents, FLT3 inhibitors, and hematopoietic stem cell transplants. Data were presented last month at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting by lead investigator Naval G. Daver, M.D., Associate Professor in the Department of Leukemia at MD Anderson Cancer Center, showing tuspetinib delivers single agent responses without prolonged myelosuppression or life-threatening toxicities in these very ill and heavily pretreated relapsed or refractory AML patients. Responses were observed in a broad range of mutationally-defined populations, including those with mutated forms of NPM1, MLL, TP53, NRAS, KRAS, DNMT3A, RUNX1, wild-type FLT3, ITD or TKD mutated FLT3, various splicing factors, and other genes.

Importantly, Aptose has elucidated a rationale for the superior safety profile of tuspetinib. While several kinase inhibitors require high exposures that exert near complete suppression of a single target to elicit responses, those agents often cause additional toxicity because they also cause extensive inhibition of that target in normal cells. In contrast, tuspetinib simultaneously suppresses a small suite of kinase-driven pathways critical for leukemogenesis. Consequently, tuspetinib achieves clinical responses at lower exposures with less overall suppression of each pathway, thereby avoiding many of the toxicities observed with competing agents.

The APTIVATE expansion trial is designed to confirm monotherapy activity through patient enrichment of specific mutationally defined AML populations, including TP53-mutant patients and FLT3-mutant patients who have been failed by a prior FLT3 inhibitor, as supported by FDA fast-track designation and a clinically significant response rate to date. In the APTIVATE expansion trial, tuspetinib also will be tested in combination with venetoclax. More information on the APTIVATE trial can be found on www.clinicaltrials.gov (here).

"We are pleased to have dosing underway in our APTIVATE clinical trial of tuspetinib in a very ill R/R AML population," said William G. Rice, Ph.D., Chairman, President, and Chief Executive Officer. "Tuspetinib has demonstrated noteworthy safety and mutation agnostic potency across a spectrum of AML patients with a diversity of adverse mutations, further distinguishing it from competing compounds and targeting a much larger AML population. This breadth of activity along with its significant safety profile has allowed us to define a precise clinical and commercial plan for tuspetinib in multiple lines of therapy, including its use in doublet and triplet combinations, as well as maintenance therapy."