On May 25, 2023 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that positive data from the Phase 1 portion of its Acclaim-1 clinical trial evaluating REQORSA Immunogene Therapy in combination with Tagrisso in late-stage non-small cell lung cancer (NSCLC) were published in an abstract at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2023 in Chicago, IL and online (Press release, Genprex, MAY 25, 2023, View Source [SID1234632059]).

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"We are thrilled to have our abstract, which reports positive results from the Phase 1 portion of our Acclaim-1 clinical trial, published at the ASCO (Free ASCO Whitepaper) Annual meeting," said Mark Berger, MD, Chief Medical Officer at Genprex. "We are encouraged by the favorable safety profile of REQORSA, as well as the preliminary efficacy data we have observed, and we believe this data will support our advancement to the Phase 2 portion of the clinical trial."

Details of the abtract are below:

Abstract Number: e15081

Title: ACCLAIM-1 dose escalation: Determination of quaratusugene ozeplasmid and osimertinib recommended phase 2 dose (RP2D)

Session Title: Publication Only: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

The abstract reports preliminary results from eight patients in Genprex’s Phase 1 portion of its Acclaim-1 clinical trial evaluating REQORSA Immunogene Therapy (quaratusugene ozeplasmid) with Tagrisso (osimertinib) in patients with advanced, EGFR mutant NSCLC whose disease progressed after Tagrisso. REQORSA was generally well tolerated, as there were no dose limiting toxicities. Full safety and efficacy data on the Phase 1 portion of the study will be presented at an upcoming medical meeting.

While the Phase 1 portion of the clinical trial is designed primarily to assess safety, promising efficacy results were also observed. One patient at the 0.06 mg/kg dose level, previously treated with carboplatin, pemetrexed, and osimertinib, had a partial remission (PR) by investigator evaluation and treatment is ongoing after 16 cycles, which is approximately 10.5 months. Another patient at the 0.09 mg/kg dose level, previously treated with osimertinib, has stable disease and treatment is ongoing after 14 cycles, or approximately 9 months. The extended and ongoing progression free survival (PFS) of each of these patients is significantly greater than the median PFS observed from treatment with osimertinib alone in this treatment setting in several prior clinical trials1 and is consistent with long-term PFS seen in prior clinical trials of REQORSA. PFS is the primary endpoint of both the Phase 2 expansion portion and the Phase 2 randomized portion of the Acclaim-1 trial.

"Demonstrating a favorable safety profile substantially de-risks the REQORSA development program and is a major accomplishment for Genprex," said Rodney Varner, Chairman, President and Chief Executve Officer of Genprex. "It is encouraging that several patients who were progressing on their previous therapy are now having long periods of response and stable disease in the Phase 1 portion of the study. We wish to thank the patients and investigators participating in our clinical trials and our investors who make it possible to move our drug candidates forward toward availability for patients in need."

1. CHRYSALIS-2 NSCLC clinical trial data reported at ASCO (Free ASCO Whitepaper) 2022

About Acclaim-1

The Acclaim-1 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA, in combination with Tagrisso in patients with late-stage NSCLC with activating epidermal growth factor receptor ("EGFR") mutations whose disease progressed after treatment with Tagrisso.

The enrollment of the dose escalation Phase 1 portion of the Acclaim-1 trial has been completed. The Phase 2 expansion portion of the study is expected to enroll approximately 66 patients, half of whom will have received only Tagrisso treatment and the other half will have received Tagrisso treatment and chemotherapy, to determine toxicity profiles of patients with different eligibility criteria, as well as efficacy and other endpoints. There will be an interim analysis following the treatment of 19 patients in each cohort. The Phase 2 randomized portion of the study is expected to enroll approximately 74 patients to be randomized 1:1 to receive either REQORSA and Tagrisso combination therapy or platinum-based chemotherapy. The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization to progression or death. An interim analysis will be performed at 25 events.

About REQORSA Immunogene Therapy

REQORSA Immunogene Therapy (quaratusugene ozeplasmid) for non-small cell lung cancer (NSCLC) uses Genprex’s unique, proprietary ONCOPREX Nanoparticle Delivery System, which is the first systemic gene therapy delivery platform used for cancer in human clinical trials. The active agent in REQORSA is a plasmid that expresses the TUSC2 tumor suppressor gene. REQORSA consists of the TUSC2 gene expressing plasmid encapsulated in non-viral lipid nanoparticles made from lipid molecules with a positive electrical charge. REQORSA is injected intravenously and specifically targets cancer cells. Once REQORSA is taken up into a cancer cell, the TUSC2 gene is expressed, and the TUSC2 protein is capable of restoring certain defective functions arising in the cancer cell. REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells.

Tagrisso is a registered trademark of AstraZeneca plc and is its top-selling drug with 2022 sales of more than $5 billion.

On May 25, 2023 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago, IL and virtually, June 2-6, 2023, and at the 2023 European Hematology Association (EHA) (Free EHA Whitepaper) Congress, being held in Frankfurt, Germany and virtually, June 8-11, 2023 (Press release, Genmab, MAY 25, 2023, View Source [SID1234632058]).

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Presentations will include data from clinical trials evaluating the efficacy of epcoritamab 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 large B-cell lymphoma (LBCL), and relapsed or refractory follicular lymphoma (FL). The safety and efficacy of epcoritamab has not been established for these investigational uses.

All abstracts accepted for presentation have been published and may be accessed online via the ASCO (Free ASCO Whitepaper) Meeting Library and EHA (Free EHA Whitepaper) Open Access Library.

"The data being presented this year at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) demonstrate Genmab’s significant progress towards our mission to develop targeted antibody therapies with the goal of improving the lives of people impacted by hematologic malignancies," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "Together with AbbVie, we are committed to evaluating epcoritamab as a potential therapy for a variety of B-cell lymphomas through a robust clinical development program."

Genmab has also submitted abstracts evaluating epcoritamab, for potential presentation at the International Conference on Malignant Lymphoma, taking place June 13-17, 2023, in Lugano, Switzerland.

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

Epcoritamab:

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
7506 Epcoritamab + R2 regimen and responses in high-risk follicular lymphoma, regardless of POD24 status. R. W. Merryman, et al. Oral Tuesday, June 6, 2023, 11:45 AM CDT
7525 Effect of follow-up time on the ability of subcutaneous epcoritamab to induce deep and durable complete remissions in patients with relapsed/refractory large B-cell lymphoma: Updated results from the pivotal EPCORE NHL-1 trial; Y. Karimi, et al. Poster Monday, June 5, 2023, 08:00 AM – 11:00 AM CDT
7519 Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: Updated EPCORE NHL-2 data; L. Falchi, et al. Poster Discussion Monday, June 5, 2023, 1:15 PM CDT
7592 Phase 3 trial of subcutaneous epcoritamab + R-CHOP versus R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL): EPCORE DLBCL-2. L. Sehn, et al. Poster Monday, June 5, 2023, 08:00 AM – 11:00 AM CDT
e18919 Practice efficiency of treatment with epcoritamab versus glofitamab in relapsed/refractory diffuse large B-cell lymphoma. D. Huang, et al. Publication NA
Real-World Evidence:

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
7552 Real-world outcomes with novel therapies in R/R DLBCL. J. Crombie, et al. Poster Monday, June 5, 2023, 08:00 AM – 11:00 AM CDT
e19530 Racial and ethnic representation in large B-cell lymphoma trials and real-world databases. J. Munoz, et al. Publication NA
Abstracts accepted for presentation at EHA (Free EHA Whitepaper) include:

Epcoritamab:

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
S222 Epcoritamab with rituximab + lenalidomide (R2) provides durable responses in patients with high-risk follicular lymphoma, regardless of POD24 status. A. Sureda, et al. Oral Friday, June 9, 2023, 15:15 PM – 15:30 PM CEST
P1116 High complete metabolic response rates with epcoritamab + R-CHOP in previously untreated (1L) patients with high-risk diffuse large b-cell lymphoma, including double/triple-hit: EPCORE NHL-2 update. M. Clausen, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1118 Longer follow-up from the pivotal EPCORE NHL-1 trial reaffirms subcutaneous epcoritamab induces deep, durable complete remissions in patients with relapsed/refractory large B-cell lymphoma. W. Jurczak, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1149 Comparison of the efficacy of epcoritamab versus chimeric antigen receptor therapies, polatuzumab-based regimens, and tafasitamab-based regimens. A. Rosenthal, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1154 Efficacy of subcutaneous epcoritamab vs axi-cel in R/R DLBCL CAR T-naive and CAR T-eligible patients: an indirect comparison. G. Salles, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1169 Comparison of real-world clinical outcomes in patients with relapsed/refractory large B-cell lymphoma treated with epcoritamab vs chemoimmunotherapy. A. Mutebi, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1176 Clinical outcomes of novel therapies in relapsed/refractory diffuse large B-cell lymphoma. T. Wang, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
GEN3014 (HexaBody-CD38):

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
P816 Pharmacodynamic activity of GEN3014 (Hexabody-CD38) in patients with multiple myeloma supports enhanced complement dependent cytotoxicity of GEN3014 compared to daratumumab. I. Hiemstra, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
About Epcoritamab
Epcoritamab-bysp is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. 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 is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration.

Epcoritamab was recently approved in the U.S. under the brand name EPKINLYTM and is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after 2 or more lines of systemic therapy.

This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In October 2022, Genmab announced that AbbVie submitted a Marketing Authorization Application for epcoritamab for the treatment of patients with R/R DLBCL after two or more lines of systemic therapy, which was validated by the European Medicines Agency. Additionally, in December 2022, Genmab announced that the company submitted a Japan new drug application to the Ministry of Health, Labor and Welfare of Japan for epcoritamab for the treatment of patients with R/R LBCL after two or more lines of systemic therapy.

Genmab and AbbVie are continuing to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes an ongoing phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494), an ongoing phase 3, open-label, randomized trial evaluating epcoritamab in combination in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R follicular lymphoma (FL) (NCT: 05409066). Please visit clinicaltrials.gov for more information.

U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNINGS

Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving EPKINLY (epcoritamab-bysp). Initiate treatment with the EPKINLY step-up dosing schedule to reduce the incidence and severity of CRS. Withhold EPKINLY until CRS resolves or permanently discontinue based on severity.
Immune effector cell–associated neurotoxicity syndrome (ICANS), including life-threatening and fatal reactions, can occur with EPKINLY. Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold EPKINLY until ICANS resolves or permanently discontinue based on severity.
Cytokine Release Syndrome (CRS)

EPKINLY can cause CRS, including serious or life-threatening reactions. CRS occurred in 51% of patients at the recommended dose in the clinical trial (37% grade 1, 17% grade 2, and 2.5% grade 3). Recurrent CRS occurred in 16% of patients. Of all the CRS events, most (92%) occurred during cycle 1. In cycle 1, 9% of CRS events occurred after the 0.16 mg dose (cycle 1, day 1), 16% after the 0.8 mg dose (cycle 1, day 8), 61% after the 48 mg dose (cycle 1, day 15), and 6% after the 48 mg dose (cycle 1, day 22). The median time to onset of CRS from the most recently administered EPKINLY dose across all doses was 24 hours (range, 0-10 days). The median time to onset after the first full 48 mg dose was 21 hours (range, 0-7 days). CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range, 1-27 days).
Signs and symptoms of CRS can include pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia.
Initiate EPKINLY according to the step-up dosing schedule. Administer pretreatment medications to reduce the risk of CRS and monitor patients for potential CRS. Following administration of the first 48 mg dose, patients should be hospitalized for 24 hours. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate. Withhold or discontinue EPKINLY based on the severity of CRS.
Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
Immune Effector Cell–Associated Neurotoxicity Syndrome (ICANS)

EPKINLY can cause life-threatening and fatal ICANS. ICANS occurred in 6% (10/157) of patients in the clinical trial (4.5% grade 1, 1.3% grade 2, 0.6% fatal: 1 event). Of the 10 ICANS events, 9 occurred in cycle 1 of treatment. The median time to onset was 16.5 days (range, 8-141 days) from the start of treatment. Relative to the most recent administration, the median time to onset was 3 days (range, 1-13 days). The median duration of ICANS was 4 days (range, 0-8 days), with ICANS resolving in 90% of patients with supportive care.
Signs and symptoms of ICANS can include confusional state, lethargy, tremors, dysgraphia, aphasia, and nonconvulsive status epilepticus. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
Monitor for potential ICANS. At the first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or discontinue EPKINLY per recommendations and consider further management per current practice guidelines.
Patients who experience signs or symptoms of ICANS or any other adverse reactions that impair cognition or consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
Infections

EPKINLY can cause serious and fatal infections. In the clinical trial, serious infections, including opportunistic infections, were reported in 15% of patients treated with EPKINLY at the recommended dose (14% grade 3 or 4, 1.3% fatal). The most common grade 3 or greater infections were sepsis, COVID-19, urinary tract infection, pneumonia, and upper respiratory tract infection.
Monitor patients for signs and symptoms of infection prior to and during treatment with EPKINLY and treat appropriately. Avoid administration of EPKINLY in patients with active infections.
Prior to starting EPKINLY, provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis and consider prophylaxis against herpes virus.
Withhold or consider permanent discontinuation of EPKINLY based on severity.
Cytopenias

EPKINLY can cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia. Among patients who received the recommended dose in the clinical trial, grade 3 or 4 events occurred in 32% (decreased neutrophils), 12% (decreased hemoglobin), and 12% (decreased platelets). Febrile neutropenia occurred in 2.5%.
Monitor complete blood counts throughout treatment. Based on severity of cytopenias, temporarily withhold or permanently discontinue EPKINLY. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.
Embryo-Fetal Toxicity

EPKINLY may cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose.

Adverse Reactions

The most common (≥20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

Lactation

Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.

Please see the full Prescribing Information and Medication Guide, including Boxed Warnings.

On May 25, 2023 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion" or the "Company"), a clinical-stage biotechnology company specializing in the discovery and development of AI-powered immunotherapies, reported the technology behind its novel, proprietary genetic adjuvant developed to enhance the effectiveness of DNA and mRNA vaccines for infectious diseases and cancer (Press release, Evaxion Biotech, MAY 25, 2023, View Source [SID1234632057]).

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Latest data from the adjuvant program were presented at Evaxion’s live stream R&D Day, May 25, 2023.

"We are excited to present this novel genetic adjuvant technology to the global scientific community. It boosts Evaxion´s own DNA technology and has the potential to improve the effect of virtually any vaccine. We foresee a great market potential in that this technology appears to be highly effective in both DNA and mRNA based vaccines against cancer as well as infectious diseases." said Per Norlén, CEO at Evaxion.

Evaxion´s novel genetic adjuvant carries the code for CCL19, a molecule known to attract immune cells, notably antigen presenting cells, and can be encoded into either DNA or mRNA vaccines with the aim of boosting the immune response.

Latest data show that the genetic adjuvant technology boosts the antitumor effect in preclinical tumor models, and induces neutralizing antibodies and T-cell responses against both viral and bacterial antigens:

1. Delivery of DNA or mRNA cancer neoantigen vaccines induced strong neoantigen-specific T-cell responses and complete antitumor responses

2. Delivery of a COVID-19 T-cell epitope DNA vaccine resulted in a strong and specific T-cell response and protected against a lethal dose of the virus (90% survival)

3. Delivery of a Neisseria Gonorrhoeae antigen DNA vaccine induced high antibody titers and specific T-cell responses towards the bacterial antigens

Per Norlén continues, "By encoding the immune-stimulating molecule CCL19 into either DNA or mRNA vaccines, we have demonstrated significant enhancement of the vaccines effectiveness. We believe that this advancement holds immense potential for vaccine development, as it boosts both B cell and T cell immune responses, making it applicable to a wide range of vaccines. Building on the encouraging preclinical results, the next step is to validate the technology in patients."

Evaxion aims to bring the genetic adjuvant technology into clinical trials later this year as part of the personalized cancer immunotherapy program EVX-03.

Please visit the Investors section of Evaxion’s website to access a replay of the R&D Day presentations.

On May 25, 2023, Erasca, Inc. (the Company) reported promising preliminary data for ERAS-007 combinations in patients with gastrointestinal malignancies as part of two poster presentations that will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Erasca, MAY 25, 2023, View Source [SID1234632056]).

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In the Phase 1b/2 HERKULES-3 trial in patients with metastatic BRAF V600E mutated colorectal cancer (CRC), promising preliminary clinical activity of ERAS-007 in combination with encorafenib and cetuximab (EC) include*:

•
40% (2/5) response rate and 60% (3/5) disease control rate (CR+PR+SD) in EC-naïve response evaluable patients at the highest dose of ERAS-007 tested (100 mg BID-QW (twice daily on day 1 of each week)), with duration of exposure for both responders > 34 weeks as of the data cutoff date; across all dose levels in EC-naïve response evaluable patients, 29% (2/7) response rate and 57% (4/7) disease control rate;
•
ERAS-007 in combination with EC was generally well-tolerated with mostly low-grade treatment-related adverse events at all combination doses tested;
•
one dose-limiting toxicity (DLT) was reported for ERAS-007 100 mg BID-QW in combination with EC (Grade 3 macular edema, N=1); and
•
pharmacokinetic (PK) exposures of ERAS-007, encorafenib, and cetuximab were comparable to monotherapy values, suggesting no clinically significant PK drug-drug interactions between the study drugs.

* Data cutoff date of March 23, 2023.

The Company expects additional HERKULES-3 Phase 1b combination data in EC-naïve patients with BRAF-mutated CRC between H2 2023 and H1 2024.

In the Phase 1b/2 HERKULES-3 trial in patients with KRAS/NRAS mutant CRC or KRASm pancreatic ductal adenocarcinoma (PDAC), preliminary results from ERAS-007 in combination with palbociclib demonstrated a lack of clinical activity in patients with KRAS/NRAS mutant CRC and KRAS mutant PDAC. Based on these data, the Company will not pursue the combination of ERAS-007 and palbociclib in this patient population.

On may 25, 2023 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported four poster presentations at the upcoming 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago, Illinois on June 2-6, 2023 (Press release, Deciphera Pharmaceuticals, MAY 25, 2023, View Source [SID1234632054]).

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"As we prepare to initiate our INSIGHT pivotal Phase 3 study of QINLOCK versus sunitinib in second-line GIST patients with KIT exon 11 and 17/18 mutations, we are excited to share details on the study design and additional supporting data from the INTRIGUE study. Our exploratory analysis from INTRIGUE using baseline circulating tumor DNA (ctDNA) showed that QINLOCK provided clinically meaningful benefit in patients with co-occurring KIT exon 11 and 17/18 mutations, with a median progression-free survival of 14.2 months compared to 1.5 months for sunitinib," said Matthew L. Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. "QINLOCK has the clear potential to become the standard-of-care for these second-line GIST patients and provide exceptional clinical benefit compared to the current standard of care."

Dr. Sherman continued, "We are also pleased to report overall survival and long-term safety data for our INTRIGUE Phase 3 study. In the all-patient intent-to-treat population, overall survival was 35.5 months in the QINLOCK arm and 30.9 months in the sunitinib arm. The favorable safety profile was consistent with our primary analysis, with fewer patients on QINLOCK experiencing Grade 3/4 treatment-emergent adverse events compared to sunitinib. Separately, our analysis from the INTRIGUE study showed better clinical outcomes for patients without detectable ctDNA at baseline, and among these patients without baseline ctDNA, ripretinib showed a median PFS of 16.6 months compared to 11.0 months for patients in the sunitinib arm."

Copies of the posters are currently available on the Company’s website at www.deciphera.com/presentations-publications. Presentation details are as follows:

Abstract Number: 11524
Title: Overall survival and long-term safety in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: Updated analyses from INTRIGUE.
Presenter: Robin L. Jones, M.D., Consultant Medical Oncologist, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research
Session Date: Saturday, June 3
Session Time: 1:15 – 4:15 PM CT
Poster Discussion Session: 4:30 – 6:00 PM CT
Key Highlights:

INTRIGUE is a randomized, open-label, global, multicenter phase 3 study comparing the efficacy and safety of ripretinib vs. sunitinib in patients with GIST who had disease progression on, or were intolerant to, first-line treatment with imatinib
453 patients were randomized 1:1 to receive ripretinib 150 mg QD or sunitinib 50 mg QD (4 weeks on/2 weeks off) and were stratified by KIT mutational status and imatinib intolerance
51 of 444 treated patients (11.5%; intent-to-treat population (ITT)) remain on treatment; 33/223 (14.8%) on ripretinib and 18/221 (8.1%) on sunitinib
Overall survival (OS) was measured at the second interim analysis (IA) as of September 1, 2022, with 185 OS events (41%) in the ITT population and 133/327 (41%) in the KIT exon 11 ITT population
OS was similar with ripretinib vs. sunitinib in the ITT population (median 35.5 months vs. 30.9 months; HR 0.88; 95% CI, 0.66 to 1.18; nominal P = 0.39) and KIT exon 11 ITT population (median 34.0 months vs. 31.5 months; HR 1.05; 95% CI, 0.75 to 1.48; nominal P = 0.77)
PFS on next line of therapy in the second IA was similar with ripretinib vs. sunitinib in the all patient (AP) ITT population (median 7.7 months vs. 6.5 months; HR 1.01; 95% CI, 0.76 to 1.34) and KIT exon 11 ITT population (median 8.2 months vs. 7.5 months; HR 1.14; 95% CI, 0.81 to 1.59)
The updated safety profile was consistent with the primary analysis
Fewer patients had grade 3/4 treatment-emergent adverse events (TEAEs) with ripretinib vs. sunitinib (95 [42.6%] vs. 149 [67.4%])
Dose interruptions, and reductions, and treatment discontinuations due to TEAEs were lower with ripretinib vs. sunitinib
The most common TEAEs of any grade in the ripretinib arm were alopecia, fatigue, and myalgia, whereas the most common TEAEs of any grade in patients treated with sunitinib were palmar-plantar erythrodysesthesia syndrome, diarrhea, and hypertension
Abstract Number: 11536
Title: Outcomes in patients with advanced gastrointestinal stromal tumor who did not have baseline ctDNA detected in the INTRIGUE study
Presenter: Jonathan Trent, M.D., Ph.D., Associate Director for Clinical Research, Sylvester Comprehensive Cancer Center, University of Miami Health System
Session Date: Saturday, June 3
Session Time: 1:15 – 4:15 PM CT
Key Highlights:

An exploratory objective in the INTRIGUE Phase 3 study was to evaluate anti-tumor efficacy of QINLOCK according to baseline KIT primary and secondary mutational status using circulating tumor DNA (ctDNA)
Data cutoff was September 1, 2021 for all data except OS, which had a data cutoff of September 1, 2022
Of the 453 patients in the ITT population, baseline ctDNA was analyzed in 362 patients for whom evaluable samples were available
Among 82 patients (22.7%) who had no detectable ctDNA (ctDNA-ND), 40 were in the ripretinib arm and 42 in the sunitinib arm
Among the 280 patients (77.3%) with ctDNA detected (ctDNA-D), 135 were in the ripretinib arm and 145 in the sunitinib arm
Clinical efficacy was higher in patients with ctDNA-ND vs. ctDNA-D
Objective response rate (ORR) rate was higher in patients with ctDNA-ND (25.6%) vs. ctDNA-D (17.5%)
Progression-free survival (PFS) was higher in patients with ctDNA-ND (12.3 months) vs. ctDNA-D (6.8 months), HR 1.81; 95% CI, 1.28 to 2.56; nominal P = 0.0006
Overall survival (OS) was higher in patients with ctDNA-ND (not estimable) vs. ctDNA-D (28.9 months), HR 4.69; 95% CI, 2.54 to 8.68; nominal P < 0.0001
In the ctDNA-ND group, ripretinib demonstrated a numerically higher PFS vs. sunitinib (median 16.6 months vs. 11.0 months; HR 0.73; 95% CI, 0.39 to 1.39; nominal P = 0.3362) and in the ctDNA-D group. PFS was comparable between ripretinib and sunitinib (median 6.8 months vs. 6.9 months; HR 1.23; 95% CI, 0.92 to 1.64; nominal P = 0.1583)
In the ctDNA-ND group, OS was similar with ripretinib vs. sunitinib (not estimable for both ripretinib and sunitinib; HR 0.84; 95% CI, 0.25 to 2.75; nominal P = 0.7674) and in the ctDNA-D group (median 27.7 months vs. 29.5 months; HR 1.05; 95% CI, 0.75 to 1.47; nominal P = 0.7609)
Patients with ctDNA-ND were younger (median 55.5 years vs. 62.0 years) and had smaller sums of longest diameters of target lesions vs. patients with ctDNA-D
Safety was similar between ctDNA groups and consistent with the primary analysis
Fewer patients had grade 3/4 TEAEs with ripretinib vs. sunitinib in both groups (ctDNA-ND, 14 [35.0%] vs. 29 [69.0%]; ctDNA-D, 56 [41.5%] vs. 94 [65.7%])
Dose interruptions, dose reductions, and treatment discontinuations due to TEAEs were lower with ripretinib vs. sunitinib
Abstract Number: TPS11582
Title: INSIGHT: A phase 3, randomized, multicenter, open-label study of ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib harboring KIT exon 11 + 17 and/or 18 mutations.
Presenter: Suzanne George, M.D., Associate Division Chief, Sarcoma Center, Dana-Farber Cancer Institute
Session Date: Saturday, June 3
Session Time: 1:15 – 4:15 PM CT
Key Highlights:

INSIGHT is an international, Phase 3, randomized, multicenter, open-label study to evaluate the efficacy of ripretinib vs. sunitinib in patients with advanced GIST previously treated with imatinib and who have KIT exon 11 mutations and co-occurring mutations exclusively in KIT exon 17 and/or 18
54 participants will be randomized 2:1 to either ripretinib 150 mg once daily (QD; continuous) or sunitinib 50 mg QD (4 weeks on/2 weeks off) in 6-week cycles
Patients will receive the study drug until disease progression determined by independent radiologic review (IRR) using modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v.1.1), unacceptable toxicity, or withdrawal of consent
Upon disease progression as determined by blinded IRR, patients in the sunitinib arm may crossover to receive ripretinib
The primary outcome measure is progression-free survival based on blinded IRR
Abstract Number: 397784*
Title: Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE
Presenter: Sebastian Bauer, M.D., Head of Sarcoma Center and Translational Sarcoma Research at the West German Cancer Center, University Hospital Essen, University Duisburg-Essen and German Cancer Consortium
Session Date: Saturday, June 3
Presentation Time: 1:54 – 2:00 PM CT
Key Highlights:

In patients with a KIT exon 11 primary mutation identified by the planned exploratory analysis from INTRIGUE:
52 patients had additional mutations in KIT exon 17/18 only
41 patients had additional mutations in KIT exon 13/14 only
22 patients had additional mutations in both KIT exon 13/14 and exon 17/18
Patients with mutations in KIT exon 11 and exon 17/18 only derived substantially improved clinical benefit with ripretinib compared to sunitinib
Ripretinib demonstrated a median PFS (mPFS) of 14.2 months compared to 1.5 months for the sunitinib arm (HR 0.22, nominal P <0.0001)
Ripretinib demonstrated a confirmed objective response rate (ORR) of 44.4% (n=12 of 27) compared to 0% for sunitinib (nominal P = 0.0001)
OS for the ripretinib arm has not reached a median, while patients randomized to the sunitinib arm had a median OS (mOS) of 17.5 months (HR 0.34, nominal P = 0.0061)
Patients with mutations in KIT exon 11 and 13/14 only derived substantially improved clinical benefit with sunitinib compared to ripretinib
Ripretinib demonstrated an mPFS of 4.0 months compared to 15.0 months for the sunitinib arm (HR 3.94, nominal P = 0.0005)
Ripretinib demonstrated a confirmed ORR of 9.5% compared to 15% for sunitinib (nominal P = 0.5922)
Ripretinib demonstrated a mOS of 24.5 months, while mOS for patients randomized to sunitinib was not estimable (HR 1.75, nominal P = 0.2085)
* ASCO (Free ASCO Whitepaper) Plenary Series: Rapid Abstract Update

About the INSIGHT Study

The planned INSIGHT Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib with mutations in KIT exon 11 and 17/18 only (excluding patients with mutations in KIT exons 9, 13, or 14). In the study, 54 patients will be randomized 2:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. The primary endpoint is PFS as determined by independent radiologic review using modified RECIST 1.1 criteria. Secondary endpoints include ORR as determined by independent radiologic review using modified RECIST 1.1 criteria and OS.

About the INTRIGUE Study

The INTRIGUE Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib. In the study, 453 patients were randomized 1:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. As previously reported, the study did not achieve the primary efficacy endpoint of PFS as determined by independent radiologic review using modified RECIST 1.1 criteria. The statistical analysis plan included a hierarchical testing sequence that included testing patients with a KIT exon 11 primary mutation and then in the all patient intent-to-treat (AP) population. In patients with a KIT exon 11 primary mutation (n=327), QINLOCK demonstrated an mPFS of 8.3 months compared to 7.0 months for the sunitinib arm (HR 0.88, p=0.360). Although not formally tested due to the rules of the hierarchical testing sequence, in the AP population QINLOCK demonstrated a mPFS of 8.0 months compared to 8.3 months for the sunitinib arm (HR 1.05, nominal p=0.715). QINLOCK was generally well tolerated. Fewer patients in the QINLOCK arm experienced Grade 3-4 treatment-emergent adverse events compared to sunitinib (41.3% vs. 65.6%).