On MAY 26, 2022 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating several investigational medicines in the company’s pipeline, or created using Genmab’s innovative drug development platforms, will be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held at McCormick Place, in Chicago, IL, and virtually, June 3-7 (Press release, Genmab, MAY 26, 2022, View Source [SID1234615085]). The presentations will include data from multiple arms of the phase 1b/2 EPCORE NHL-2 clinical trial, evaluating the safety and preliminary efficacy of epcoritamab (DuoBody-CD3xCD20), an investigational subcutaneous bispecific antibody, in combination with standard-of-care therapies for the treatment of various types of B-cell non-Hodgkin lymphoma (NHL), including first-line, high-risk diffuse large B-cell lymphoma (DLBCL), relapsed or refractory DLBCL, and relapsed or refractory follicular lymphoma (FL). Epcoritamab is being co-developed by Genmab and AbbVie (NYSE: ABBV).

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In addition, several abstracts evaluating tisotumab vedotin (TIVDAK) in various tumor types will be presented, including an oral presentation of the innovaTV 205 study evaluating tisotumab vedotin in combination with carboplatin or pembrolizumab in first-line patients with recurrent or metastatic cervical cancer (r/mCC). Tisotumab vedotin is being co-developed by Genmab and Seagen (Nasdaq: SGEN), under an agreement in which the companies share costs and profits for the product on a 50:50 basis.

Results from several clinical trials evaluating Janssen Biotech, Inc. (Janssen’s) subcutaneous formulation of daratumumab, and Janssen’s bispecific programs leveraging Genmab’s DuoBody technology platform, will be presented. Daratumumab is being developed by Janssen under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab, and the companies have a research and license agreement to create and develop bispecific antibodies using Genmab’s DuoBody technology platform.

All abstracts accepted for presentation have been published on the ASCO (Free ASCO Whitepaper) website.

"This year’s ASCO (Free ASCO Whitepaper) provides a great opportunity for Genmab to share data evaluating epcoritamab, our first-in-class approved medicine tisotumab vedotin, and our innovative technologies, which reinforce our commitment to delivering new therapeutic options to patients in need," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "Through our own research and development, and through industry partnerships, Genmab is developing differentiated therapies with the goal of transforming the future of cancer treatment."

Abstracts accepted for presentation at ASCO (Free ASCO Whitepaper) include:

Epcoritamab (DuoBody-CD3xCD20):

Abstract #: 7523. First-line treatment with subcutaneous (SC) epcoritamab (epco) + R-CHOP in patients (pts) with high-risk diffuse large B-cell lymphoma (DLBCL): phase 1/2 data update; Falchi et al. Saturday, June 4, 2022, 8:00-11:00 a.m. CDT/9:00 p.m.-12:00 p.m. EDT.
Abstract #: 7524. Subcutaneous epcoritamab with rituximab + lenalidomide (R2) in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): update from phase 1/2 trial; Falchi et al. Saturday, June 4, 2022, 8:00-11:00 a.m. CDT/9:00 p.m.-12:00 p.m. EDT.
Abstract #: 7528. Subcutaneous epcoritamab + R-DHAX/C in patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) eligible for autologous stem cell transplant (ASCT): preliminary phase 1/2 results; Abrisqueta et al. Saturday, June 4, 2022, 8:00-11:00 a.m. CDT/9:00 p.m.-12:00 p.m. EDT.
Abstract #: 7527. Epcoritamab (epco) with gemcitabine + oxaliplatin (GemOx) in patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) induces high response rate even in pts failing CAR T therapy; Brody et al. Saturday, June 4, 2022, 8:00-11:00 a.m. CDT/9:00 p.m.-12:00 p.m. EDT.
Abstract #: 7576. DLBCL Cell of Origin Typing and Whole Transcriptome Analysis using Single Slides with HTG EdgeSeq; Loya, et al. Saturday, June 4, 2022, 8:00-11:00 a.m. CDT/9:00 p.m.-12:00 p.m. EDT.
Tisotumab Vedotin:

Abstract #: 5507. Tisotumab vedotin (TV) + pembrolizumab (pembro) in first-line (1L) recurrent or metastatic cervical cancer (r/mCC): Interim results of ENGOT Cx8/GOG 3024/innovaTV 205; D. Lorusso et al. Monday, June 6, 2022, 8:00-11:00 a.m. CDT/9:00 a.m.-12:00 p.m. EDT.
Abstract#: TPS5603. Trial in progress update on ENGOT-cx8/GOG-3024/innovaTV 205: Addition of a new cohort of tisotumab vedotin (TV) + pembrolizumab (pembro) + carboplatin (carbo) ± bevacizumab (bev) in first line (1L) recurrent/metastatic cervical cancer (r/mCC); I. Vergote et al. Saturday, June 4, 2022, 1:15-4:15 p.m. CDT/2:15-5:15 p.m. EDT.
Abstract #: TPS6100. innovaTV 207: New combination dosing cohorts in the open label phase 2 study of tisotumab vedotin in solid tumors; X. Le et al. Monday, June 6, 2022, 1:15-4:15 p.m. CDT/2:15 p.m.-5:15 p.m. EDT.
Abstract #: 5532. Factors Associated with Receipt of Second-Line Recurrent or Metastatic Cervical Cancer Treatment in the US: A Retrospective Administrative Claims Analysis; K. Sonawane et al. Saturday, June 4, 2022, 1:15-4:15 p.m. CDT/2:15-5:15 p.m. EDT.
Abstract #: 5523. Cervical Cancer Geographical Burden Analyzer: An Interactive, Open-Access Tool For Understanding Geographical Disease Burden in Recurrent or Metastatic Cervical Cancer Patients; T. Castellano et al. Saturday, June 4, 2022, 1:15-4:15 p.m. CDT/2:15-5:15 p.m. EDT
Abstract #: E17520. Productivity losses under various second-line recurrent or metastatic cervical cancer treatment scenarios in the US; T. Ayer et al.
Abstract #: E17525. Patterns of Care in Medicaid-Enrollees with recurrent or metastatic Cervical Cancer; C. A. Leath et al.
Daratumumab:

Subcutaneous daratumumab (DARA SC) versus active monitoring in patients (pts) with high-risk smoldering multiple myeloma (SMM): randomized, open-label, phase 3 AQUILA study; Dimopoulos et al.
Time to response, duration of response, and patient-reported outcomes (PROs) with daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) vs lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): subgroup analysis of the phase 3 MAIA study; Facon et al.
Efficacy and safety of daratumumab (DARA) in pediatric and young adult patients (pts) with relapsed/refractory T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL): results from the phase 2 DELPHINUS study; Hogan et al.
Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in Black patients (pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): an updated subgroup analysis of GRIFFIN; Nooka et al.
Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM): a post hoc analysis of sustained minimal residual disease (MRD) negativity from GRIFFIN; Rodriguez et al.
Daratumumab (DARA) in combination with bortezomib plus dexamethasone (D-Vd) or lenalidomide plus dexamethasone (D-Rd) in relapsed or refractory multiple myeloma (RRMM): subgroup analysis of the phase 3 CASTOR and POLLUX studies in patients (pts) with early or late relapse after initial therapy; Spencer et al.
About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.i Epcoritamab was developed with selective, silencing mutations that may limit systemic, non-specific activity.ii CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.iii,iv Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

About Tisotumab Vedotin
Tisotumab vedotin-tftv (TIVDAK) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

In September 2021, the U.S. Food and Drug Administration granted accelerated approval for tisotumab vedotin-tftv (TIVDAK) in adult patients with previously treated recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, making it the first and only approved ADC for these patients. The ongoing clinical trial InnovaTV 301, an open label, randomized, global trial, is intended as the confirmatory trial for use in verifying and describing the clinical benefit and as support for US and global regulatory applications.

TIVDAK (tisotumab vedotin-tftv) U.S Indication & Important Safety Information
TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

BOXED WARNING: OCULAR TOXICITY
TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Warnings and Precautions
Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8 % of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose. In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral Neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barre syndrome. Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients. Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Embryo-Fetal Toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions
In the innovaTV 204 clinical trial (n=101), serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug interactions

Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

Please see full prescribing information, including BOXED WARNING for TIVDAK here.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration approval to treat certain multiple myeloma indications. Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. The subcutaneous formulation of daratumumab (daratumumab and hyaluronidase-fihj) is the first subcutaneous CD38 antibody approved for the treatment of certain multiple myeloma indications and the first and only approved treatment for certain patients with light-chain (AL) amyloidosis.v,vi,vii

Please see local country prescribing information for all labeled indication and safety information.

On May 26, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported top-line clinical data from its Phase 1/2 trial of galinpepimut-S (GPS), the Company’s Wilms Tumor-1 (WT1)-targeting peptide immunotherapeutic, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients diagnosed with WT1(+) relapsed or refractory platinum resistant advanced metastatic ovarian cancer (Press release, Sellas Life Sciences, MAY 26, 2022, View Source [SID1234615101]).

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Data from 15 patients enrolled in the study, conducted under a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc., Rahway, N.J., USA (known as MSD outside the United States and Canada), has been preliminarily analyzed with final data for all 17 patients enrolled in the clinical trial expected by the end of 2022. All enrolled patients were resistant to standard of care platinum-based therapy and 78.5 percent of evaluable patients were refractory to or had failed their first- or second-line therapies with 21.5 percent having failed three or more lines of therapy, including one patient who failed five previous lines of therapy. Of the 15 patients, 13 received at least three doses of GPS, the last of which was in combination with pembrolizumab, and were evaluable for response outcomes.

Summary of Top-Line Clinical Data

The overall response rate (ORR) of the trial is (7.7 percent), similar to the response to checkpoint inhibitors.
An ad hoc analysis of clinical outcomes in this cohort shows a disease control rate (DCR), the sum of overall response rate and rate of stable disease, of 53.9 percent at a median follow-up of 43.1 weeks. In a checkpoint inhibitor single agent study in a similar platinum-resistant ovarian cancer patient population treated with a checkpoint inhibitor alone, the observed DCR was 37.2 percent, consistent with a DCR rate increase of 45 percent in the GPS combination with pembrolizumab over that seen for checkpoint inhibitors alone.
Median progression-free survival (PFS) was 12 weeks compared to 8.4 weeks for checkpoint inhibitors alone seen in studies with similar patient populations, a 43 percent increase in the GPS combination with pembrolizumab. Patients with fewer previous lines of chemotherapy experienced a more favorable median PFS than those with more than two previous lines: for patients with two or fewer previous lines of therapy treated with GPS in combination with pembrolizumab, median PFS was 24 weeks.
With 43.1 weeks of follow-up the median overall survival has not been reached.
The safety profile of GPS in combination with pembrolizumab was similar to pembrolizumab alone, with the only addition of low-grade rapidly resolving local reactions at the GPS injection site, consistent with observations from other GPS clinical studies.
"These early data are an example of a new direction in development of immunotherapy for platinum-refractory ovarian cancer," commented Jeffrey S. Weber, M.D., Ph.D.; Deputy Director of the Perlmutter Cancer Center at New York University (NYU)-Langone Health; Co-Director of its Melanoma Research Program Center; and Chair of SELLAS’ Scientific Advisory Board. "In patients who failed as many as five lines of previous therapy, with small numbers of patients, the disease control rate and progression free survival that were observed merit further study. The GPS combination with checkpoint blockade, such as pembrolizumab, should be further explored, both in active disease as well as potentially in the setting of maintenance therapy after patients reach minimal residual disease post salvage therapies," added Dr. Weber.

"GPS has been primarily designed as maintenance therapy in order to provide an overall survival benefit after patients reach the minimal residual disease state or complete remission. However, in this very difficult to treat patient population with active disease, who underwent intensive chemotherapies with no apparent clinical benefit and a severe toxicity toll, the combination of GPS and pembrolizumab seems to be effective in the active disease state by halting or slowing down progression without significant further side effects," said Angelos Stergiou, M.D., Sc.D. h.c., President and CEO, SELLAS.

"As we continue to do further analyses, including immune response and correlative analyses, which will be presented at an upcoming medical conference, we are also considering how to best pursue development of GPS in combination with PD1 inhibitors in this patient population and we are excited about the path ahead. I would like to wholeheartedly thank all patients for participating in the study as well as their physicians, nurses and study teams as well as collectively our teams at SELLAS and Merck," concluded Dr. Stergiou.

About Ovarian Cancer
Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women in the United States. Over 22,000 cases are diagnosed annually, and there are an estimated 15,500 deaths per year. The majority of patients have widespread disease at presentation. The 5-year survival for advanced-stage disease remains less than 30 percent. Combining GPS with the checkpoint inhibitor pembrolizumab, which beneficially and profoundly alters the tumor microenvironment (TME) is hypothesized to increase the proportion of patients who develop an immune response against their cancer and potentially improve their clinical outcome over checkpoint inhibitors monotherapy, without the burden of additional toxicities in macroscopically measurable malignancies.

On May 26, 2022 Novocure (NASDAQ: NVCR) reported it has entered into a clinical trial collaboration agreement with MSD, a tradename of Merck & Co., Inc., Rahway, NJ, USA, to study the use of Tumor Treating Fields (TTFields) concomitant with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of patients with newly diagnosed glioblastoma (GBM) (Press release, NovoCure, MAY 26, 2022, View Source [SID1234615117]). This is the second clinical collaboration between Novocure and MSD.

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"We are excited to collaborate again with global oncology leader, MSD, in the pursuit of extending survival in some of the most aggressive forms of cancer," said William Doyle, Novocure’s Executive Chairman. "EF-41/Keynote D58 will build on encouraging preliminary data from the 2-THE-TOP phase 2 pilot study and will further explore recently published data suggesting the potential for a therapeutic benefit when TTFields are used together with immunotherapy due to TTFields’ downstream immune system activation and anti-tumor cell response. Through the EF-41/Keynote D58 trial, we hope to identify a potential new treatment option for solid tumor cancers and we are thrilled at the prospect of improving outcomes for patients in need."

Novocure and MSD plan to conduct a double-blind, placebo-controlled study of TTFields concomitant with KEYTRUDA and maintenance temozolomide (TMZ) versus TTFields together with placebo and maintenance TMZ for the treatment of adult patients with newly diagnosed GBM. Novocure intends to engage FDA in the near term in a pre-submission discussion regarding the details of the agreed upon study.

ABOUT 2-THE-TOP

The EF-41/Keynote D58 trial will build on encouraging preliminary data from the 2-THE-TOP phase 2 pilot study. The 2-THE-TOP trial is an investigator-initiated, phase 2 pilot trial evaluating the use of TTFields therapy together with pembrolizumab and chemotherapy (temozolomide) for the treatment of 26 adult patients with newly diagnosed GBM. In March 2022, updated data from the ongoing 2-THE-TOP study was presented at the World Federation of Neuro-oncology Societies (WFNOS) 2022 Quadrennial Meeting, comparing outcomes for 26 patients in the 2-THE-TOP study versus a historical, matched-control group of 26 patients from the TTFields plus temozolomide arm of the phase 3 pivotal EF-14 clinical trial. Patients in the 2-THE-TOP trial displayed median progression-free survival (primary endpoint) of 12.1 months and median overall survival of 25.2 months, which are based on a median follow-up time of 16.8 months. Additionally, 193,760 peripheral blood mononuclear cells were sequenced in 12 patients before pembrolizumab was administered and detected robust post-TTFields T cell activation in 11 of 12 patients via the T1IFN trajectory with a strong correlation with the TCRαβ clonal expansion Simpson index (Spearman coefficient r=-0.8, P=0.014).

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division. Fundamental scientific research extends across more than two decades and, in all preclinical research to date, TTFields have demonstrated a consistent anti-mitotic effect. TTFields therapy is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields therapy has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 24,000 patients have been treated with TTFields therapy.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On May 26, 2022 Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and biologic cancer therapeutics, reported new data from the ongoing Phase 1b clinical trial studying RGX-202-01 in combination with FOLFIRI and bevacizumab (FOLFIRI/BEV) in second-line advanced colorectal cancer (CRC) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 3-7 in Chicago, Illinois (Press release, Inspirna, MAY 26, 2022, View Source [SID1234615133]).

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"These exciting new data show the potential of RGX-202-01 to drive meaningful responses in patients with advanced or metastatic colorectal cancer, especially in the KRAS mutant setting where there is a clear opportunity to improve on the standard of care," said Andrew Hendifar, M.D., Assistant Professor at Cedars-Sinai Medical Center and principal investigator on the study. "RGX-202-01 employs a novel mechanism by inhibiting SLC6a8, part of a pathway that becomes activated by colorectal cancer cells in order for these cells to survive, proliferate, and metastasize. Importantly, along with its preliminary signal of efficacy, these results also demonstrate that RGX-202-01 is very well-tolerated, enabling it to be combined with FOLFIRI/BEV and provide further optionality in this difficult-to-treat indication."

RGX-202-01 is an oral, potential first-in-class small molecule inhibitor of SLC6a8, a creatine transporter that drives colorectal cancer and certain other cancers’ progression. It is currently being evaluated in a Phase 1b dose escalation and expansion study in combination with FOLFIRI/BEV in second-line, advanced or metastatic CRC. The primary endpoint of the study is to determine maximum tolerated dose (MTD), overall response rate (ORR), and treatment-emergent adverse events (TEAEs). In the dose escalation stage of the study, two dose levels of RGX-202-01 with FOLFIRI/BEV have been evaluated in patients with advanced or metastatic CRC who have progressed on available oxaliplatin based first line therapy. In the ongoing expansion stage, additional patients with CRC are being treated at the dose of 3000mg PO BID to provide further characterization of the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the treatment.

Key findings to be presented at ASCO (Free ASCO Whitepaper) 2022:

The data cutoff for the presentation is April 28, 2022. As of data cutoff, 19 patients were enrolled in the study, including eight total patients in the dose escalation stage treated with either 2400mg twice daily (BID) of RGX-202-01 plus FOLFIRI/BEV (n = 4) or 3000mg BID RGX-202-01 plus FOLFIRI/BEV (n = 4), and 11 patients treated in the expansion stage with 3000mg BID RGX-202-01 plus FOLFIRI/BEV.
The dose escalation stage did not reach an MTD.
No dose limiting toxicities (DLT) were observed at either 2400mg BID or 3000mg BID doses.
There were only two Grade 4 TEAEs, and one of those was considered unrelated to treatment with RGX-202-01, and no Grade 5 TEAEs were observed.
17 patients were evaluable for response per RECIST v1.1 at data cutoff, of which 10 patients had KRAS mutant tumors and seven patients had KRAS wild-type tumors.
In the KRAS mutant population, five patients (50%) had confirmed partial responses (PR) and five patients (50%) had stable disease (SD).
In the KRAS wild-type population, one patient (14%) had an unconfirmed PR, five patients (71%) had SD, and one patient (14%) had progressive disease (PD).
Preliminary median progression-free survival (mPFS) was 11.8 months in the enrolled patients with KRAS mutant tumors.
Tumor regression was observed to deepen over time in patients with KRAS mutant tumors, with first radiographic achievement of PR appearing as late as 40 weeks post-treatment induction.
Overall, results show ORR and mPFS exceed expected benefit with standard-of-care alone in second-line CRC.
"We are very encouraged by the data reported today showing a strong signal of activity and meaningful responses, especially in patients harboring KRAS mutant tumors," said Masoud Tavazoie, M.D., Ph.D., Chief Executive Officer of Inspirna. "The results not only support our efforts to continue advancing RGX-202-01 in CRC, but also validate the ability of our RNA-DRIVEr platform to discover and develop new drug candidates with the potential to address cancers of high unmet medical need. We look forward to sharing these results at ASCO (Free ASCO Whitepaper) and further advancing RGX-202-01 drug development."

The abstract is available for viewing on the ASCO (Free ASCO Whitepaper) website, and the poster will be available at View Source following the session.

Poster Presentation Details

Title: Phase 1b study of RGX-202-01, a first-in-class oral inhibitor of the SLC6A8/CKB pathway, in combination with FOLFIRI and bevacizumab (BEV) in second-line advanced colorectal cancer (CRC)

Date and time: Saturday, June 4, 2022, 8:00 a.m. CDT

Session: Gastrointestinal Cancer—Colorectal and Anal

Abstract ID: 3579

On May 26, 2022 Laekna Therapeutics, a clinical-stage biotechnology company developing innovative medicines to treat cancer and liver diseases, reported that two first patients have been dosed in the U.S. and China, respectively, in a Phase Ib/III clinical trial that evaluates the efficacy and safety of afuresertib in combination with fulvestrant, an estrogen receptor antagonist, in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who failed after 1-2 lines of CDK4/6 inhibitors, endocrine, or chemotherapy treatments (Press release, Laekna Therapeutics, MAY 26, 2022, View Source;breast-cancer-301555843.html [SID1234615149]).

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Afuresertib is an investigational AKT kinase inhibitor with global exclusive rights obtained from Novartis. The lead investigator of the study in China is Professor Binghe Xu, Academician of the Chinese Academy of Engineering and Director of the National Clinical Research Center for Cancer, while Professor Peter Kaufman, Lead Medical Oncologist from The University of Vermont Medical Center, is the lead investigator of the study in the U.S. Patient enrollment has begun simultaneously at the Piedmont Cancer Institute in the U.S. and Tianjin Medical University Cancer Institute & Hospital in China, and will soon begin in several other sites. Laekna will initiate a Phase III global pivotal trial after afuresertib plus fulvestrant shows a manageable safety profile in the Phase Ib study.

Breast cancer is the most common cancer among women worldwide. About 62% and 68% of all breast cancer patients in China and the U.S. are HR+/HER2- respectively[1,2]. "Although most patients with this type of breast cancer initially benefit from endocrine ±CDK4/6 inhibitors and/or chemotherapy as first- or second-line treatment, resistance occurs in most patients in about two years. I look forward to the results from the clinical study of afuresertib in combination with fulvestrant, which could offer a new treatment option for treatment-resistant breast cancer," said Professor Xu.

"Our team has been working closely with the investigators to overcome obstacles and dose the first patients both in the U.S. and China according to schedule, which demonstrated Laekna’s robust global clinical development capabilities," said Dr. Yong Yue, Chief Medical Officer of Laekna Therapeutics. "Our next step is to expedite simultaneous global development of afuresertib plus fulvestrant to bring hope to patients who have developed treatment resistance."