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%).

On May 25, 2023 Cullinan Oncology, Inc. (Nasdaq: CGEM), a biopharmaceutical company focused on modality-agnostic targeted oncology therapies, reported first monotherapy clinical data from its Phase 1 study of CLN-619 in patients with advanced solid tumors (Press release, Cullinan Oncology, MAY 25, 2023, View Source [SID1234632053]). Findings from the clinical trial will be shared at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting as a poster presentation during the "Developmental Therapeutics—Immunotherapy" session (poster # 2532) on June 3, 2023 from 8:00 AM-11:00 AM Central Time. CLN-619 is being studied in an ongoing Phase 1 clinical trial both as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.

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Summary of Key Clinical Results from Monotherapy Arm of Phase 1 Clinical Trial in Patients with Solid Tumors:
•
Monotherapy dose escalation demonstrates acceptable safety profile of CLN-619 across all doses assessed (0.1, 0.3, 1, 3, 6, 10mg/kg):

•
No dose-limiting toxicities were observed

•
Consistent with other monoclonal antibodies, infusion-related reactions were limited to the first dose and all grade 1/2 in patients receiving mandated pre-medication

•
Data demonstrate monotherapy anti-tumor activity of CLN-619, including objective tumor responses, across multiple tumor types:

All Patients
(n=37) Response Evaluable1
at ≥1 mg/kg
(n=22) Response Evaluable1
GYN Malignancy2
(n=10)
Complete Response (CR)

1 1 0
Partial Response (PR)3

2 2 2
Stable Disease (SD)

7 7 5
CR + PR + SD

10 10 7
Progressive Disease (PD)

18 12 3
Not Evaluable (NE)

9 NA NA

1
Patients who underwent at least one RECIST response assessment or who had clinically assessed PD prior to first planned response assessment

2
Endometrial, cervical, and ovarian

3
The observed partial responses were unconfirmed but ongoing at time of data cut-off

•
One CR was observed in a patient with parotid gland cancer whose cancer had progressed on prior checkpoint inhibitor therapy

•
Two PRs (pending confirmation) were observed in patients with endometrial cancer, one whose cancer had progressed on prior checkpoint inhibitor therapy

•
Stable disease was observed in patients across multiple tumor types, including cervical, ovarian, salivary gland, and breast cancers

•
Patients were heavily pre-treated with a median of 3 prior systemic therapies (1 – 7), and 54% had received prior immune checkpoint inhibitor therapy

•
The trial continues to enroll in both the monotherapy and combination arms.

"We are encouraged by the first clinical data for CLN-619 monotherapy, which demonstrates broad potential across a range of tumor types. Objective responses and sustained stable disease were observed, including in patients whose tumors had relapsed on or were not amenable to checkpoint inhibitor therapy," said Jeffrey Jones, MD, MPH, MBA, Chief Medical Officer, Cullinan Oncology. "Notably, clinical activity was observed in multiple gynecologic cancer types of high unmet need. Based on these initial efficacy observations, we will initiate expansion cohorts in endometrial and cervical cancer and look to expand in additional tumor-specific cohorts as the data matures. Additionally, the Phase 1 trial continues to evaluate CLN-619 in combination with pembrolizumab, and we look forward to sharing the results at a future medical meeting."

"These data demonstrate the potential of CLN-619 to treat a range of solid tumors. Along with the monotherapy efficacy of CLN-619, we also observed a favorable safety profile, with most adverse events being grade 2 or lower" said Judy Wang, MD, Florida Cancer Specialists and Research Institute. "We need new ways to help overcome immune evasion mechanisms, and CLN-619 is an antibody that is designed to render cancer cells visible to the immune system by binding to MICA and MICB, stress-induced ligands that engage the activating receptor NKG2D present on both innate and adaptive immune cells, representing a novel approach to enable immune-mediated elimination of tumors."

"Over 66,000 new cases of endometrial cancer are diagnosed every year in the United States. The incidence has been rising for more than a decade, particularly in the more aggressive subtypes, and uterine cancer is projected to surpass colorectal cancer as the fourth leading cause of cancer death among women by 2040.1,2 Despite recent advances in endometrial cancer therapeutics, this patient population is often affected by other co-morbidities, so safer and more effective treatment options are urgently needed to address a growing unmet need" said Vicky Makker, MD, Section Head of the Endometrial Cancer Program at Memorial Sloan Kettering Cancer Center. "That need extends across gynecologic cancers. In cervical cancer, treatment options remain limited, and even with improvements in screening to reduce incidence rates, approximately 13,000 new cases of cervical cancer are diagnosed annually and greater than 4,000 women die of this malignancy each year in the U.S.3"

CLN-619 Further Development Plan

CLN-619 is being studied in an ongoing Phase 1 clinical trial both as a monotherapy and in combination with pembrolizumab. The study design allows dose level extensions as well as expansion in tumor-specific cohorts. Consistent with prespecified criteria and based on initial safety and efficacy observations, Cullinan will initiate monotherapy expansion cohorts in endometrial cancer and cervical cancer. Additional expansion cohorts may be initiated based upon clinical activity observed in the current trial.

Virtual and Live Investor Event

Cullinan Oncology will host an Investor Event on Sunday, June 4, 2023, at 7:00 am Central Time, during which Dr. Jeff Jones, Chief Medical Officer at Cullinan Oncology, will present an overview of CLN-619 data shared at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting, and Dr. Vicky Makker, MD, Section Head of the Endometrial Cancer Program at Memorial Sloan Kettering Cancer Center, will share an overview of the current treatment landscape for endometrial cancer. Investors and analysts are invited to register to attend in-person by emailing Chad Messer, VP Investor Relations ([email protected]). A live webcast will be available via the events page of the Company’s investor relations website at View Source, and a replay will be available shortly after the conclusion of the live event.

About CLN-619

CLN-619 is a potential first-in-class humanized IgG1 monoclonal antibody that binds to the stress induced ligands, MICA and MICB, which are expressed on a wide variety of solid tumors and hematological malignancies. Engagement of MICA/B by the activating receptor NKG2D, present on both cytotoxic innate and adaptive immune cells, results in target cell lysis. However, tumor cells can shed MICA/B via proteases they release into the tumor microenvironment, resulting in evasion of immune-mediated destruction. CLN-619 functions by restoring MICA/B expression on the surface of tumor cells, enhancing the interaction between MICA and NKG2D, and inducing antibody-dependent cellular toxicity (ADCC), together promoting anti-tumor activity via multiple immune-mediated mechanisms. CLN-619 is being studied in an ongoing Phase 1 clinical trial both as a monotherapy and in combination with pembrolizumab. The study design allows dose level extensions as well as expansion in tumor-specific cohorts.

On May 25, 2023 CatalYm reported that the first results from its ongoing Phase 2a trial "GDFATHER-2" (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 2) will be featured in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2023 in Chicago (Press release, Catalym, MAY 25, 2023, View Source [SID1234632052]). The trial is evaluating CatalYm’s lead GDF-15 neutralizing antibody visugromab in combination with immune checkpoint inhibitor nivolumab in last-line, anti-PD-1/PD-L1 relapsed/refractory patients. Growth and differentiation factor 15 (GDF-15) is recognized as a negative regulator of antitumoral T cell activity preventing T cell recruitment to the tumor microenvironment as well as potently suppressing an adaptive immune response by additional mechanisms recently identified. The ASCO (Free ASCO Whitepaper) Annual Meeting will be held in Chicago, Illinois, from June 2 to 6, 2023.

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Oral presentation details:

Presentation Title: Initial results from the phase 2a trial of visugromab (CTL-002) + nivolumab in advanced/metastatic anti-PD1/-L1 relapsed/refractory solid tumors (The GDFATHER-TRIAL)
Presenter: Dr. Ignacio Melero Bermejo, MD | Clinica Universidad de Navarra
Session: Developmental Therapeutics-Immunotherapy
Session Date and Time: Sunday, June 4, 2023, from 9:45 AM – 12:45 PM CDT
Location: In-Person | Arie Crown Theater | McCormick Place | Live Stream
Presentation Number: 2501

The full abstract details can be accessed via View Source The company will provide further information and a summary of the data following the oral presentation at ASCO (Free ASCO Whitepaper).

On May 25, 2023 Carina Biotech (Carina), a cell therapy immuno-oncology company, reported that the management team will participate in the three upcoming conferences as follows (Press release, Carina Biotech, MAY 25, 2023, View Source [SID1234632051]):

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9th Annual Immuno-Oncology Innovation Forum will be held in person in Chicago on June 2. Deborah Rathjen, Carina’s Chief Executive Officer, is scheduled to participate in the Competing in the Cell & Gene Therapy Space panel on June 2 at 11:20 am CT. The Carina team plans to host meetings and present on Friday, June 2 at 2:35 pm CT.

2023 ASCO (Free ASCO Whitepaper) Annual Meeting will be held in person in Chicago and online from June 2-6. The Carina team will be sharing a poster presentation showcasing its Phase 1/2a clinical trial of its LGR5-targeted CAR-T cell therapy candidate CNA3103 in patients with metastatic colorectal cancer (mCRC).
Poster Details
Title: A phase 1/2a, multicenter, open-label study of CNA3103 (LGR5-targeted, autologous CAR-T cells) in patients with metastatic colorectal cancer (mCRC)
Lead Author: José Iglesias, MD, Carina’s Chief Medical Officer
Session Type/Title: Poster Session – Gastrointestinal Cancer—Colorectal and Anal
Session Date and Time: Monday June 5, 2023 from 8:00 AM CDT – 11:00 AM CDT
Published Abstract Number: TPS3632

2023 BIO International Convention will be held in-person in Boston from June 5-8. The Carina team will host meetings at the event.
(Download pdf here)

About CNA3103

Carina’s proprietary CNA3103 CAR-T cell targets LGR5, a cancer stem cell marker that is highly expressed on advanced colorectal cancer and some other cancers. In colorectal cancer patients, LGR5 expression has been correlated with poor prognosis. Cancer stem cells are a small sub-population of cells within a tumor with the ability to self-renew, differentiate into the many cell types of a tumor, initiate new tumors, and resist chemotherapy and radiotherapy (leading to relapses). By targeting cancer stem cells, it is hoped that this therapy will reduce the tumor’s ability to generate new cancer cells, resulting in durable tumor suppression and preventing the relapses that are very common in patients with colorectal cancer. Carina’s pre-clinical studies of CNA3103 have shown promising results with complete tumor regression and no tumor recurrence following a single administration. CNA3103 has also demonstrated impressive tumor access and prolonged survival, enabling rejection of new tumors.

On May 25, 2023 Bristol Myers Squibb (NYSE: BMY) reported the first disclosure of results from the primary analysis of the pivotal TRANSCEND CLL 004 study, a Phase 1/2, open-label, single-arm multicenter study evaluating Breyanzi (lisocabtagene maraleucel, liso-cel) in adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, Bristol-Myers Squibb, MAY 25, 2023, View Source [SID1234632050]). At a median follow-up of 21.1 months, results show that Breyanzi delivered statistically significant complete response (CR) rates, the study’s primary endpoint, in 18.4% of patients in the primary efficacy analysis set (95% CI: 8.8-32; p=0.0006). Among patients who achieved a CR, no disease progression or deaths were observed, with median duration of response not reached.

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TRANSCEND CLL 004 is the first pivotal multicenter study of a CD19-directed CAR T cell therapy for patients with relapsed or refractory CLL after progression on a BTKi and BCL2i. These data will be presented in an oral presentation during the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 6, 10:45 a.m. EDT (Abstract #7501).

There is a critical unmet need for patients with relapsed or refractory CLL or SLL, especially those who have experienced disease progression after treatment with a BTKi and BCL2i. These patients often have high-risk disease features and poor outcomes, with short overall survival. Current treatment options rarely provide complete responses, and durability of response is limited.

"For people living with relapsed or refractory CLL or SLL after treatment with BTKi and BCL2i-based regimens, there is no standard of care treatment. Achieving deep and lasting remission in this situation is challenging as most patients experience disease progression despite continuous treatment," said Tanya Siddiqi, M.D., lead investigator and Associate Professor, Division of Lymphoma, City of Hope National Medical Center. "The durable complete responses observed with liso-cel in the TRANSCEND CLL 004 trial are remarkable and represent a major step in bringing a personalized, T-cell-based treatment approach delivered as a one-time infusion into clinical practice for a complex and historically incurable disease."

"Results from TRANSCEND CLL 004 reinforce our relentless commitment to bringing the potential of CAR T cell therapy to more patients and transforming the treatment and outcomes for a broad range of hematologic malignancies," said Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb. "Breyanzi has shown clinically meaningful benefit across the broadest array of B-cell malignancies of any CD19-directed CAR T cell therapy and we remain dedicated to advancing innovative treatments for some of the most difficult-to-treat diseases with high unmet need."

The TRANSCEND CLL 004 trial included a broad population of patients with relapsed or refractory CLL or SLL with high unmet need who had received at least two prior lines of therapy, including a BTKi (n=117). The prespecified primary efficacy analysis set (PEAS; n=49) consisted of a subset of patients who had experienced disease progression following treatment with a BTKi and failure of BCL2i-based regimens, representing a patient population with advanced and aggressive disease, and who were treated with the target dose of 100 x 106 CAR-positive viable T-cells of Breyanzi. High rates of undetectable minimal residual disease (uMRD) were observed across patients treated with Breyanzi, with a uMRD rate 63.3% in the blood (95% CI: 48.3-76.6) and 59.2% in the bone marrow (95% CI: 44.2-73.0), which was associated with an increase in progression-free survival.The overall response rate (ORR) was 42.9% (95% CI: 28.8-57.8; p=0.3931), with a median duration of response of 35.3 months (11.01-NR). Data were consistent between the PEAS and the broad patient population evaluated in the study, including heavily pretreated patients with a median of five prior lines of therapy (2 – 12) and high-risk disease, with a CR rate of 18.4% (95% CI: 10.9-28.1), demonstrating the clinical benefit of Breyanzi for a broad patient population with relapsed or refractory CLL or SLL.

Among all treated patients in the study (n=117), including subgroups of heavily pretreated patients, Breyanzi exhibited a manageable safety profile, and no new safety signals were observed. Any grade cytokine release syndrome (CRS) occurred in 84.6% of patients, with Grade 3 CRS occurring in 8.5% of patients. No Grade 4/5 CRS events were reported. Any grade neurologic events (NE) were reported in 45.3% of patients, with Grade 3 NE reported in 17.9% of patients and one case (0.9%) of Grade 4 NE reported. No Grade 5 NE were reported.

Results from TRANSCEND CLL 004 will be discussed with health authorities. Bristol Myers Squibb thanks the patients and investigators involved in the TRANSCEND CLL 004 trial.

About TRANSCEND CLL 004
TRANSCEND CLL 004 (NCT03331198) is a Phase 1/2 open-label, multicenter study evaluating Breyanzi in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The Phase 1 dose escalation portion of the study assessed the safety and recommended dose for the subsequent Phase 2 expansion cohort. The Phase 2 portion of the study is evaluating Breyanzi at the recommended dose from the Phase 1 monotherapy arm. The primary endpoint of the Phase 2 portion of the study was complete response rate, including complete remission with incomplete bone marrow recovery, based on independent review committee according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines.

About CLL and SLL
Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults. In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes, and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells and platelets. Small lymphocytic lymphoma (SLL) also affects the lymphocytes, with cancer cells found mostly in the lymph nodes. While there are several treatments available for CLL and SLL, there is no standard of care for relapsed or refractory CLL or SLL after prior therapy with targeted agents, which raises the need for additional effective therapies. Patients with relapsed or refractory disease have limited treatment options and generally experience shorter periods of response with each subsequent treatment.

About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment. Breyanzi is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with LBCL, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant due to comorbidities or age, or relapsed or refractory disease after two or more lines of systemic therapy. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding cytokine release syndrome and neurotoxicity.

Breyanzi is also approved in Japan and Europe for the second-line treatment of relapsed or refractory LBCL, and in Japan, Europe, Switzerland, and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma and leukemia. For more information, visit clinicaltrials.gov.

U.S. Important Safety Information
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
relapsed or refractory disease after two or more lines of systemic therapy.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome (CRS)
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS occurred in 46% (190/418), including ≥ Grade 3 CRS (Lee grading system) in 3.1% of patients.

In patients receiving BREYANZI after two or more lines of therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade 3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 98% with a median duration of 5 days (range: 1 to 17 days).

In patients receiving BREYANZI after one line of therapy for LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3% of patients. The median time to onset was 4 days (range: 1 to 63 days). CRS resolved in all patients with a median duration of 4 days (range: 1 to 16 days).

The most common manifestations of CRS (≥10%) included fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).

Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.

Of the 418 patients who received BREYANZI for LBCL, 23% received tocilizumab and/or a corticosteroid for CRS, including 10% who received tocilizumab only and 2.2% who received corticosteroids only.

Neurologic Toxicities
Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.

In patients receiving BREYANZI after two or more lines of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), including ≥ Grade 3 in 12% of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of neurotoxicity was 8 days (range: 1 to 46 days). Neurologic toxicities resolved in 85% with a median duration of 12 days (range: 1 to 87 days).

In patients receiving BREYANZI after one line of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of patients, including Grade 3 cases in 7% of patients. The median time to onset of neurologic toxicities was 8 days (range: 1 to 63 days). The median duration of neurologic toxicity was 6 days (range: 1 to 119 days).

In all patients combined receiving BREYANZI for LBCL, neurologic toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in 10% of patients. The median time to onset was 8 days (range: 1 to 63), with 87% of cases developing by 16 days. Neurologic toxicities resolved in 85% of patients with a median duration of 11 days (range: 1 to 119 days). Of patients developing neurotoxicity, 77% (105/136) also developed CRS. The most common neurologic toxicities (≥ 5%) included encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).

CRS and Neurologic Toxicities Monitoring
Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.

BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer
BREYANZI are trained on the management of CRS and neurologic toxicities.

Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions
Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections
Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion.

In patients receiving BREYANZI for LBCL, infections of any grade occurred in 36% with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections occurred in 4.3%, viral infections in 1.9% and fungal infections in 0.5%.

Febrile neutropenia developed after BREYANZI infusion in 8% of patients with LBCL. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells.

In patients who received BREYANZI for LBCL, 15 of the 16 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.

Prolonged Cytopenias
Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion.

Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 36% of patients with LBCL and included thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.

Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI.

In patients receiving BREYANZI for LBCL, hypogammaglobulinemia was reported as an adverse reaction in 11% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 28% of patients.

Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies
Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Effects on Ability to Drive and Use Machines
Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks.

Adverse Reactions
The most common nonlaboratory adverse reactions (incidence ≥ 30%) are fever, CRS, fatigue, musculoskeletal pain, and nausea.

The most common Grade 3-4 laboratory abnormalities (≥ 30%) include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.

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