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IN8bio Provides Update from the Ongoing Phase 1 Clinical Trial of its Allogeneic Gamma-Delta T Cell Therapy in Leukemia Patients Undergoing Hematopoietic Stem Cell Transplant

On December 16, 2021 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative gamma-delta T cell therapies utilizing its DeltEx platform, reported an update from the ongoing Phase 1 clinical trial of INB-100, a donor-derived gamma-delta T cell therapeutic in development for patients with leukemia undergoing haploidentical hematopoietic stem cell transplant (HSCT) (Press release, In8bio, DEC 16, 2021, View Source [SID1234597303]). The three patients with relapsed acute myeloid leukemia (AML) treated to date demonstrate that allogeneic gamma-delta T cell therapy has a manageable toxicity profile with the potential for durable responses in high-risk patients. Haploidentical HSCT patients have high relapse rates of up to 50% at one-year post-treatment. All three of the INB-100 treated patients remain in remission with two patients in remission at 18 and 20 months, respectively. No treatment-related grade 3 or greater adverse events, infusion reactions or dose-limiting toxicities were observed. The trial continues to track these patients and enroll additional patients.

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"We believe that the encouraging early data from the first patients dosed in this clinical trial suggest the potential of gamma-delta T cells to offer a novel treatment option for patients with aggressive hematologic malignancies," said Trishna Goswami, MD, Chief Medical Officer at IN8bio. "Multiple complete responses with durability greater than 1.5 years is especially promising for patients with high-risk leukemias, who have high rates of post-HSCT relapse. The absence of grade 3 or greater graft versus host disease (GvHD) 100 days post gamma-delta T cell infusion is also encouraging for an allogeneic therapy. We continue to enroll patients in this Phase 1 clinical trial and look forward to reporting additional data from this program in 2022."

This Phase 1 clinical trial (NCT03533816) is a dose-escalation trial of allogeneic, or donor-derived, gamma-delta T cells that have been expanded and activated ex vivo and administered systemically to patients with leukemia following haploidentical HSCT. Three high-risk AML patients with complex cytogenetics have been treated to-date, including patients with trisomy 8, del7 mutations. The single-institution clinical trial is currently being conducted at The University of Kansas Cancer Center (KUCC). The primary endpoints of this trial are safety and tolerability, and secondary endpoints include rates of GvHD, relapse rate and overall survival.

About IN8bio

IN8bio is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of gamma-delta T cell product candidates for solid and liquid tumors. Gamma-delta T cells are a specialized population of T cells that possess unique properties, including the ability to differentiate between healthy and diseased tissue.

The proprietary IN8bio DeltEx platform is designed to overcome many of the challenges associated with the expansion, genetic engineering and scalable manufacturing of gamma-delta T cells. The DeltEx platform employs allogeneic, autologous and genetically modified approaches to develop cell therapies, designed to effectively identify and eradicate tumor cells. This approach allows us to expand the cells ex vivo to administer a potentially therapeutic dose to patients, harnessing the unique properties of gamma-delta T cells, including their ability to broadly recognize cellular stress signals on tumor cells. We have used the DeltEx platform to create our deep pipeline of innovative allogeneic, autologous and/or genetically modified product candidates designed to effectively target and potentially eradicate disease and improve patient outcomes.

IN8bio is currently conducting two investigator-initiated Phase 1 clinical trials for its lead gamma-delta T cell product candidates: INB-200 for the treatment of newly diagnosed glioblastoma and INB-100 for the treatment of patients with leukemia undergoing hematopoietic stem cell transplantation. IN8bio also has a broad portfolio of preclinical programs focused on addressing other solid tumor types.

G1 Therapeutics Announces Expansion of COSELA™ (Trilaciclib) Sales Force

On December 16, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the Company will hire and deploy an additional 20 salespeople, bringing the total number of oncology sales representatives to 34 (Press release, G1 Therapeutics, DEC 16, 2021, View Source [SID1234597302]). The expansion will allow G1 to target all accounts to accelerate sales activities and help maximize the adoption of COSELA (trilaciclib). G1 and Boehringer Ingelheim have mutually agreed to end the co-promotion agreement for COSELA, effective March 2022.

"We want to thank Boehringer Ingelheim for their support in laying the early commercial groundwork during the first year of COSELA’s availability in the U.S.," said Andrew Perry, Chief Commercial Officer of G1 Therapeutics. "We are well along in the process of hiring our COSELA-focused sales force; these experienced oncology sales professionals have existing relationships at target organizations and are prioritizing prescriber access, which is the key to execution and adoption of new therapies like COSELA. Our goal is to drive as quick an impact as possible from this effort, and as such we are hiring, training, and deploying these individuals into the field as they arrive. We have already hired 13 of these field-based professionals, deployed seven, and expect to have the full team of 34 in place and deployed by mid-February 2022."

Under the terms of the termination agreement, Boehringer Ingelheim and G1 will work together on transitioning promotional activities by March 2022. After that point, Boehringer Ingelheim will receive reduced payments based on net sales of COSELA for patients with ES-SCLC in the U.S. until March 2024. There are no payments due by either party beyond March 2024. The Co-Promotion Agreement does not extend to additional indications that G1 may pursue for trilaciclib.

Webcast and Conference Call

G1 will host a webcast and conference call at 8:30 a.m. ET today to discuss the expansion of the COSELA sales force. The live call may be accessed by dialing (866) 763-6020 (domestic) or (210) 874-7713 (international) and entering the conference code: 8549816. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

About COSELA (trilaciclib) for Injection

COSELA (trilaciclib) was approved by the U.S. Food and Drug Administration on February 12, 2021.

Indication
COSELA (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

Important Safety Information
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.

Warnings and precautions include injection-site reactions (including phlebitis and thrombophlebitis), acute drug hypersensitivity reactions, interstitial lung disease (pneumonitis), and embryo-fetal toxicity.

The most common adverse reactions (>10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

This information is not comprehensive. Please click here for full Prescribing Information. View Source

Forma Therapeutics’ Investigational Olutasidenib in Combination with Azacitidine Yields Durable Complete Remission in Patients with mIDH1 Acute Myeloid Leukemia

On December 16, 2021 Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX), a clinical-stage biopharmaceutical company focused on sickle cell disease, prostate cancer and other rare hematologic diseases and cancers, reported the company’s investigational oral, selective mIDH1 inhibitor combined with azacitidine yielded durable complete remission (CR) or CR with partial hematologic recovery (CRh) responses with favorable tolerability in patients with the mIDH1 form of acute myeloid leukemia (AML) (Press release, Forma Therapeutics, DEC 16, 2021, View Source [SID1234597301]).

These positive findings, the first Phase 2 results of olutasidenib used in combination with a chemotherapy, were presented in an oral session on Dec. 13, 2021, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The findings support the potential of olutasidenib as the basis of combination therapy in patients with AML who have not achieved a durable response from prior therapy. In addition, a poster, presented on Dec. 12 at ASH (Free ASH Whitepaper), reported on the molecular characteristics of the mIDH1 of patients in the trial who responded to olutasidenib when administered as monotherapy.

"AML is a cancer that returns in about half of patients following initial treatment. Patients who are not achieving remission or suffer from an AML relapse are in need of new therapies with more durable outcomes. The data presented today at ASH (Free ASH Whitepaper) increase our understanding of olutasidenib’s potential to achieve durable complete responses when used as either first-line or second-line therapy along with a standard therapy for patients with mIDH1 AML," said Patrick Kelly, M.D., chief medical officer of Forma Therapeutics.

The oral presentation reports an analysis of four patient cohorts from the pivotal open-label Phase 2 arm of an ongoing Phase 1/2 study, (2102-HEM-101, NCT02719574), who received olutasidenib dosed 150 milligrams (mg) twice daily continuously during 28-day cycles plus azacitidine, as of June 16, 2021. Azacitidine, a hypomethylating agent (HMA), was administered daily as an intravenous or subcutaneous injection therapy for days one to seven of each cycle.

Investigators enrolled patients into one of the four groups based on their disease status and prior therapy and recorded the best overall response for the primary endpoint of a composite complete remission (CR) plus CR with partial hematologic recovery (CRh) rate (CR/CRh). The group of patients who had not yet received therapy for their AML and were candidates for azacitidine as a first-line treatment had CR/CRh rate of 45% (5 out of 11). The other three groups enrolled patients who had relapsed/refractory AML (R/R AML) that, respectively, had prior HMA therapy; had prior therapy with an IDH1 inhibitor, including olutasidenib monotherapy; and were candidates for azacitidine as a first-line treatment. The CR/CRh rates for these groups were 38% (5 of 13), 30% (6 of 20), and 47% (9 of 19), respectively.

Olutasidenib with Azacitidine Well Tolerated

Olutasidenib was well tolerated in the trial in combination with azacitidine and the combination had a safety profile largely consistent with that of olutasidenib alone. Treatment-emergent adverse events (TEAEs) occurring in 25 percent or more of the participants included nausea (49 percent), constipation (40 percent), vomiting (35 percent), thrombocytopenia (32 percent), diarrhea (28 percent), and neutropenia (26 percent). TEAEs of grade 3 or 4 in more than 10 percent of participants included neutropenia (26 percent), thrombocytopenia (25 percent), anemia (19 percent), and febrile neutropenia (14 percent). TEAEs of QTc prolongation occurred in five participants (7 percent), of whom two experienced grade 3 QTc prolongation, and none discontinued olutasidenib.

TEAEs associated with liver enzyme abnormalities occurred in 15 participants (21 percent), with grade 3/4 in six (8 percent). Investigator-assessed IDH1 differentiation syndrome in six (8 percent) patients, of whom most resolved with treatment interruption, dexamethasone, and/or supportive treatment, while two patients had concomitant leukocytosis.

Molecular Characteristics of Response to Olutasidenib in Patients with R/R AML

A poster presentation reported findings from a planned interim analysis of the trial’s cohort of patients with R/R AML receiving olutasidenib alone, dosed 150 mg twice daily. The analysis examined expression of IDH1m variant allele frequency, prevalence of other genetic co-mutations in the trial’s pivotal cohort, and associations between mutations and response. Responses were observed across all IDH1 mutation subtypes and response rates were lower amongst patients with concurrent FLT3 co-mutations. Patients with higher co-mutations at baseline had lower rates of response than those with low mutational burden. Similarly, patients with lower baseline IDH1 expression were more likely to respond than those with high expression.

Olutasidenib Presentations Details

Abstract 698: Olutasidenib (FT-2102) in Combination with Azacitidine Induces Durable Complete Remissions in Patients with mIDH1 Acute Myeloid Leukemia.

Session 616 on Monday, Dec. 13, at 3:00 PM ET

Presenter: Jorge E. Cortes, M.D.

Abstract 2351: Molecular Characteristics of Response to Olutasidenib (FT-2102) in Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia

Session: 616 on Sunday, Dec. 12, at 6:00 PM ET

Presenter: Stéphane de Botton, M.D., Ph.D.

For more information, please visit View Source or View Source

About AML

Acute myeloid leukemia (AML) is a cancer that starts in a person’s bone marrow but often quickly moves into the blood. AML develops from immature blood cells, known as myeloid cells, that are supposed to mature into white blood cells. However, the diseased myeloid cells do not function properly. They instead multiply rapidly, which causes normal blood cell production to fail. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that about 20,940 new cases, most in adults, arose in 2021 in the United States alone.1

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.2 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.3

About Olutasidenib

Olutasidenib is an oral, potent and small molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted treatment has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6 to 8 percent of patients with AML.

Cullinan Oncology Announces Updated Phase 1/2a Data for CLN-081 in NSCLC EGFR Exon 20 Patients

On December 16, 2021 Cullinan Oncology, Inc. (Nasdaq: CGEM) ("Cullinan"), a biopharmaceutical company focused on developing a diversified pipeline of targeted therapies for cancer patients, reported updated data from the Company’s ongoing Phase 1/2a trial of CLN-081 in non-small cell lung cancer (NSCLC) patients whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations that have progressed on or after prior therapy (Press release, Cullinan Oncology, DEC 16, 2021, View Source [SID1234597297]).

"The updated data from our ongoing Phase 1/2a study in a larger number of patients further reinforce CLN-081’s differentiated clinical profile. CLN-081 has demonstrated both a high response rate and durable responses in heavily pre-treated patients," said Nadim Ahmed, Chief Executive Officer of Cullinan Oncology. "For many lung cancer patients currently receiving EGFR inhibitors, treatment related side effects can significantly impact their daily lives. In this regard, we are encouraged by CLN-081’s favorable safety profile at the 100mg BID dose."

The current analysis of the ongoing trial included a total of 73 NSCLC patients with EGFR exon 20 insertion mutations who received at least one dose of CLN-081 and were evaluable for safety as of the data cutoff. CLN-081 was administered orally, at dose levels including 30, 45, 65, 100 and 150 mg twice daily (BID). Based on prespecified safety and efficacy criteria, enrollment at the Phase 2a cohort for 100mg BID was expanded up to the planned maximum of 36 patients. Additional patients were also enrolled at the 150mg BID dose level, although enrollment was subsequently discontinued after a total of 11 patients based on overall assessment of the clinical profile at this dose level. Guided by these data,100mg BID was nominated as the Recommended Phase 2 Dose (RP2D) for CLN-081.

Efficacy Highlights:

Efficacy data from patients enrolled in the 100mg BID cohort:

Of 36 response evaluable patients, 14 achieved a confirmed PR for a 39% confirmed response rate and one additional patient had a PR that was pending confirmation at the time of the data cut-off.
The median duration of response was >15 months and the median progression free survival was 12 months in the initial cohort of phase 1 patients (N=13).
Safety and Tolerability Highlights:

Treatment related EGFR associated adverse event (AE) data for patients enrolled in the 100mg BID cohort:

Rash has been limited to Grade 1 and 2 events (54% and 18% of patients, respectively). Events were manageable with conventional supportive care and no patients have experienced Grade 3 or greater treatment-related rash.
Diarrhea has been limited to Grade 1 and 2 events (26% and 8% of patients, respectively). No prophylactic regimen has been required to ameliorate the incidence or severity of diarrhea to date, and no patients have experienced Grade 3 or greater treatment-related diarrhea.
"We are pleased with CLN-081’s safety and efficacy to date. CLN-081 has demonstrated antitumor activity among heavily pre-treated patients, including patients treated previously with other EGFR inhibitors or immunotherapy, and across a spectrum of exon 20 mutational sub-types," said Jon Wigginton, M.D., Chairman of the Cullinan Oncology Scientific Advisory Board and Senior Advisor. "We are similarly encouraged by the emerging durability data shown in this update, which we believe could also reflect the benefit of the drug’s favorable safety and tolerability profile. Our goal now is to review these results and potential future clinical development with the FDA and to move CLN-081 as expeditiously as possible into late-stage development."

Additional data are available in a presentation accompanying this press release on the Events section of our website.

About CLN-081

CLN-081 is an orally available, irreversible EGFR inhibitor that selectively targets cells expressing EGFR exon 20 insertion mutations while sparing cells expressing wild type EGFR. Cullinan is evaluating various doses of CLN-081 in a Phase 1/2a trial in patients with NSCLC harboring exon 20 mutations whose disease has progressed on or after prior therapy.

CB-103 has been granted an Orphan Designation for the treatment of Acute Lymphoblastic Leukaemia (ALL)

On December 16, 2021 Cellestia Biotech AG reported that the European Commission (EC) has granted CB-103 an orphan designation for the treatment of Acute Lymphoblastic Leukaemia (ALL) (Press release, Cellestia Biotech, DEC 16, 2021, View Source [SID1234597294]).

This is the first Orphan Designation granted to CB-103. It is an important milestone in the development of CB-103, as it represents an official recognition from EMA that CB-103 looks promising in bringing significant benefit to those affected by ALL.