On April 23, 2023, IDEAYA Biosciences, Inc. (the "Company") reported interim results from its Phase 2 clinical trial evaluating darovasertib and crizotinib synthetic lethal combination in metastatic uveal melanoma (MUM) patients, its trial design for the Phase 2/3 clinical trial evaluating darovasertib and crizotinib in first-line HLA-A2 negative MUM patients, and interim results for darovasertib as neoadjuvant therapy in primary uveal melanoma (UM), from an ongoing investigator sponsored trial (IST) evaluating darovasertib in (neo)adjuvant uveal melanoma, from compassionate use protocol(s) and from the Company’s Phase 1/2 clinical trial evaluating darovasertib as monotherapy and in combination with crizotinib (Press release, Ideaya Biosciences, APR 23, 2023, View Source [SID1234630428]).

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Clinical Data Update – Darovasertib and Crizotinib Combination in MUM

The Company observed encouraging clinical activity in the Phase 2 clinical trial evaluating the darovasertib and crizotinib combination in first-line and any-line MUM patients. The reported Phase 2 clinical data are based on 20 evaluable first-line and 63 evaluable any-line patients enrolled as of September 22, 2022 in the darovasertib and crizotinib combination study at the expansion dose of 300 mg twice-a-day darovasertib and 200 mg twice-a-day crizotinib. Reported data are preliminary and based on investigator review from an unlocked database as of the data analyses cutoff date of March 8, 2023. Enrollment in the darovasertib and crizotinib combination expansion dose cohort of the Phase 2 clinical trial is ongoing.

In the 20 evaluable first-line MUM patients in the expansion cohort, the investigator-reviewed data by RECIST 1.1 include:

45% confirmed Overall Response Rate (ORR) in first-line MUM: 9 of 20 evaluable patients had a confirmed partial response (PR)

90% Disease Control Rate (DCR) in first-line MUM: 18 of 20 evaluable patients showed disease control, including 9 confirmed PRs, 1 unconfirmed PR and 8 stable disease

~7 months median progression free survival (PFS) in first-line MUM

In the 63 evaluable any-line MUM patients at the expansion dose, the investigator-reviewed data by RECIST 1.1 include:

30% confirmed ORR in any-line MUM: 19 of 63 evaluable patients had a confirmed PR; the any-line MUM patients were heavily pre-treated, with 63% of patients having received one or more prior lines of treatment and 43% of patients having received two or more prior lines of treatment in the metastatic setting

87% DCR in any-line MUM: 55 of 63 evaluable patients showed disease control, including 19 confirmed PRs, 4 unconfirmed PRs and 32 stable disease

~7 months median PFS in any-line MUM

Observed median PFS increased versus median PFS of ~5 months previously reported in September 2022 with 35 evaluable any-line MUM patients

There were 20 evaluable hepatic-only MUM patients, including first-line and pre-treated patients with only hepatic metastases, for whom the investigator-reviewed data by RECIST 1.1 include:

35% confirmed ORR in hepatic-only MUM: 7 of 20 evaluable patients had a confirmed PR

100% DCR in hepatic-only MUM : 20 of 20 evaluable patients showed disease control, including 7 confirmed PRs, 1 unconfirmed PR and 12 stable disease

~11 months median PFS in hepatic-only MUM

These data demonstrate robust clinical efficacy of the darovasertib and crizotinib combination in first-line and any-line MUM patients.

The darovasertib and crizotinib combination has a manageable adverse event profile in MUM patients (n=68), with a low rate of drug-related serious adverse events (SAEs). Patients reported predominantly Grade 1 or 2 drug-related adverse events (AEs): 31% of patients reported at least one Grade 3 AE; no patients observed a Grade 4 AE; and one patient observed a Grade 5 AE. Four (6%) patients discontinued treatment with either darovasertib or crizotinib due to a drug-related adverse event.

FDA Guidance in Type C Meeting Supports Initiation of Potential Registrational Trial

The Company is targeting to initiate a potential registration-enabling Phase 2/3 clinical trial in Q2 2023 in first-line HLA-A2 negative MUM patients. The Phase 2/3 clinical trial design incorporates guidance and feedback from the FDA following a recent Type C meeting.

The protocol includes an integrated Phase 2/3 open-label study-in-study design in first-line MUM patients with an HLA-A*02:01 negative serotype. The clinical trial design employs a Phase 2 portion with median PFS as a primary endpoint for potential accelerated approval. Patients enrolled in Phase 2 will continue on treatment within the same clinical trial and will be considered together with additional enrolled patients to evaluate overall survival (OS) in support of a potential Phase 3 registrational trial.

In the Phase 2 portion of the clinical trial, approximately 230 patients will be randomized on a 2:1 basis for treatment with the darovasertib and crizotinib combination in the treatment arm or investigators choice in the control arm, selected from a combination of ipilimumab (ipi) and nivolumab (nivo), PD1-targeted monotherapy or DTIC. The treatment arm of the Phase 2 portion includes a nested study to confirm the move forward combination dose for the integrated Phase 2/3 clinical trial – including cohorts at the Phase 2 expansion doses of (i) darovasertib 300 mg BID + crizotinib 200 mg BID and (ii) darovasertib 200 mg BID + crizotinib 200 mg BID. Under the nested study design, patients enrolled in the cohort at the move forward dose will be included within the Phase 2/3 registrational clinical trial. The Phase 2 portion of the clinical trial contemplates an efficacy and safety data set of approximately 200 patients randomized 2:1 with the treatment arm at the move forward dose to support a potential accelerated approval based on median PFS by blinded independent central review (BICR) as a primary endpoint.

Patients enrolled in Phase 2 at the selected dose would continue on treatment and be included in the Phase 3 study analysis, supplemented by enrollment of approximately 120 additional patients into the Phase 3 portion of the clinical trial with 2:1 randomization on the same basis as the Phase 2 portion. Efficacy data from the Phase 3 could support potential approval using median OS as a primary endpoint.

Clinical Data Update – Darovasertib in (Neo)Adjuvant Primary UM

The Company observed further evidence of encouraging clinical activity for darovasertib as neoadjuvant therapy in primary UM, including responses in primary ocular tumor lesions. Data was reported from an ongoing IST evaluating darovasertib in (neo)adjuvant UM, from compassionate use protocol(s) and from the Company’s Phase 1/2 clinical trial evaluating darovasertib as monotherapy and in combination with crizotinib. Best ocular tumor response is reported based on maximal percentage reduction in measured apical height or longest basal diameter.

Collectively, these data further substantiate clinical proof of concept (POC) for the use of darovasertib in the (neo)adjuvant uveal melanoma setting:

Ocular tumor shrinkage by investigator review in 9 of 9 (100%) UM (n=6) or MUM (n=3) patients treated as monotherapy or in combination with crizotinib, including a neoadjuvant UM patient treated with darovasertib with a partial response at one month, and a second neoadjuvant UM patient treated with the darovasertib and crizotinib combination with ~80% ocular tumor shrinkage at four months who was spared enucleation, as described below.

A UM patient who was already blind in one eye from vascular disease developed a large uveal melanoma lesion in his other eye and sought neoadjuvant treatment with a goal to avoid enucleation and potentially preserve vision in the affected eye to prevent blindness. This patient, who remains on therapy, was treated with darovasertib and crizotinib combination under a compassionate use protocol. The preliminary clinical data showed:

observed ~80% ocular tumor shrinkage after four months of treatment and remains on therapy

avoided enucleation of the affected eye, which we believe to be the first reported case of systemic neoadjuvant therapy resulting in eye preservation

prompt responsiveness to treatment, including progressive tumor shrinkage, as determined by investigator measurement of tumor apical height, over each month of treatment, including approximately 30% ocular tumor shrinkage after one month, with ocular lesion size reduced to approach threshold for plaque brachytherapy, and further ocular tumor shrinkage to ~50% after two months, ~70% after three months and ~80% after four months of treatment

improved vision following course of treatment and treatment of a severe cataract: pretreatment vision score was 6/120, where 6/60 is legally blind; post-treatment vision score was 6/5, reflecting a greater than 20-fold improvement and resulting in better than normal vision. Vision scoring was based on AU meter measurement system: 6/6 m = 20/20 ft (normal vision).

The Company is initiating a company-sponsored clinical trial to evaluate darovasertib as monotherapy in (neo)adjuvant UM and is evaluating potential near-term clinical neoadjuvant endpoints such as organ preservation (avoiding enucleation) for large ocular tumors and reduction in radiation dose and/or vision preservation for small or medium ocular tumors.

The Company is also supporting St. Vincent’s Hospital Sydney Limited, which has initiated an ongoing IST captioned as "Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM) (NCT05187884), to evaluate darovasertib monotherapy in a neoadjuvant and adjuvant setting in primary UM patients.

Addressable Patient Population in MUM and UM

The potentially addressable patient population for metastatic uveal melanoma is estimated to include approximately 4,500 patients across the United States and Europe, based on estimated annual incidence, and approximately 14,000 patients in total prevalence in the United States and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib given the potential annual incidence of approximately 8,700 patients aggregate in the United States and Europe, and approximately 100,000 patients in total prevalence in the United States and Europe.

On April 23, 2023 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported further interim results from its Phase 2 clinical trial evaluating darovasertib and crizotinib combination in metastatic uveal melanoma (MUM) patients (ClinicalTrials.gov Identifier: NCT03947385) (Press release, Ideaya Biosciences, APR 23, 2023, View Source [SID1234630400]).

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"The observed efficacy in first-line metastatic uveal melanoma patients – including confirmed ORR of 45% and median PFS of ~ 7 months – is clinically significant and represents a potential paradigm shift for treating MUM patients. The interim data for the darovasertib and crizotinib combination treatment in MUM suggests a compelling clinical efficacy and tolerability profile," said Dr. Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute.

"These clinical data, considered with the FDA’s guidance from our recent Type C meeting, provides IDEAYA with a registrational trial design in first-line HLA-A2 negative MUM patients which includes a path to potential accelerated approval based on median PFS as the primary endpoint," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

There are currently no FDA approved therapies for MUM patients with HLA-A2*02:01 (HLA-A2) negative serotype. Current therapies for MUM have relatively low confirmed overall response rates and short median progression free survival (PFS), highlighting the high unmet medical need. The historical overall response rate (ORR) in MUM clinical trials has generally been reported with a confirmed ORR ranging from approximately 0% to 5%. The historical median PFS in MUM clinical trials has been reported ranging from approximately 2 to 3 months.

Darovasertib (IDE196) is a small molecule, potential first-in-class protein kinase C (PKC) inhibitor. IDEAYA is evaluating the synthetic lethal combination of darovasertib and crizotinib, a small molecule cMET inhibitor, in MUM pursuant to a clinical trial collaboration and drug supply agreement with Pfizer.

Clinical Data Update – Darovasertib and Crizotinib Combination in MUM

The company observed encouraging clinical activity in the Phase 2 clinical trial evaluating the darovasertib and crizotinib combination in first-line and any-line MUM patients. The reported Phase 2 clinical data are based on twenty (20) evaluable first-line and sixty-three (63) evaluable any-line patients enrolled in the darovasertib and crizotinib combination study at the expansion dose of 300 mg twice-a-day darovasertib and 200 mg twice-a-day crizotinib as of September 22, 2022. Reported data are preliminary and based on investigator review from an unlocked database as of the data analyses cutoff date of March 8, 2023. Enrollment in the darovasertib and crizotinib combination expansion dose cohort of the Phase 2 clinical trial is ongoing.

In the twenty (20) evaluable first-line MUM patients in the expansion cohort, the investigator-reviewed data by RECIST 1.1 include:

45% confirmed Overall Response Rate (ORR) in First-Line MUM: 9 of 20 evaluable patients had a confirmed partial response (PR)
90% Disease Control Rate (DCR) in First-Line MUM: 18 of 20 evaluable patients showed disease control, including 9 confirmed PRs, 1 unconfirmed PR and 8 stable disease
~7 months median Progression Free Survival (PFS) in First-Line MUM
In the sixty-three (63) evaluable any-line MUM patients at the expansion dose, the investigator-reviewed data by RECIST 1.1 include:

30% confirmed Overall Response Rate (ORR) in Any-Line MUM: 19 of 63 evaluable patients had a confirmed partial response (PR); the Any-Line MUM patients were heavily pre-treated, with 63% of patients having received 1 or more prior lines of treatment and 43% of patients having received 2 or more prior lines of treatment in the metastatic setting
87% Disease Control Rate (DCR) in Any-Line MUM: 55 of 63 evaluable patients showed disease control, including 19 confirmed PRs, 4 unconfirmed PRs and 32 stable disease
~7 months median Progression Free Survival (PFS) in Any-Line MUM
Observed median PFS increased versus median PFS of ~5 months previously reported in September 2022 with thirty-five (35) evaluable Any-Line MUM patients
There were twenty (20) evaluable hepatic-only MUM patients, including first-line and pre-treated patients with only hepatic metastases, for whom the investigator-reviewed data by RECIST 1.1 include:

35% confirmed Overall Response Rate (ORR) in Hepatic-Only MUM: 7 of 20 evaluable patients had a confirmed partial response (PR)
100% Disease Control Rate (DCR) in Hepatic-Only MUM: 20 of 20 evaluable patients showed disease control, including 7 confirmed PRs, 1 unconfirmed PR and 12 stable disease
~11 months median Progression Free Survival (PFS) in Hepatic-Only MUM
These data demonstrate robust clinical efficacy of the darovasertib and crizotinib combination in first-line and any-line MUM patients.

The darovasertib and crizotinib combination has a manageable adverse event profile in MUM patients (n=68), with a low rate of drug-related serious adverse events (SAEs). Patients reported predominantly Grade 1 or 2 drug-related adverse events (AEs): 31% of patients reported at least one Grade 3 AE; no patients observed a Grade 4 AE; and one patient observed a Grade 5 AE. Four (6%) patients discontinued treatment with either darovasertib or crizotinib due to a drug-related adverse event.

FDA Guidance in Type C Meeting Supports Initiation of Potential Registrational Trial

IDEAYA is targeting to initiate a potential registration-enabling Phase 2/3 clinical trial in Q2 2023 in first-line HLA-A2 negative MUM patients. The Phase 2/3 clinical trial design incorporates guidance and feedback from the FDA following a recent Type C meeting.

The protocol includes an integrated Phase 2/3 open-label study-in-study design in first-line MUM patients with an HLA-A*02:01 negative serotype. The clinical trial design employs a Phase 2 portion with median PFS as a primary endpoint for potential accelerated approval. Patients enrolled in Phase 2 will continue on treatment within the same clinical trial and will be considered together with additional enrolled patients to evaluate OS in support of a potential Phase 3 registrational trial.

In the Phase 2 portion of the clinical trial, approximately 230 patients will be randomized on a 2:1 basis for treatment with the darovasertib and crizotinib combination in the treatment arm or investigators choice in the control arm, selected from a combination of ipilimumab (ipi) and nivolumab (nivo), PD1-targeted monotherapy or DTIC. The treatment arm of the Phase 2 portion includes a nested study to confirm the move forward combination dose for the integrated Phase 2/3 clinical trial – including cohorts at the Phase 2 expansion doses of (i) darovasertib 300 mg BID + crizotinib 200 mg BID and (ii) darovasertib 200 mg BID + crizotinib 200 mg BID. Under the nested study design, patients enrolled in the cohort at the move forward dose will be included within the Phase 2/3 registrational clinical trial. The Phase 2 portion of the clinical trial contemplates an efficacy and safety data set of approximately 200 patients randomized 2:1 with the treatment arm at the move forward dose to support a potential accelerated approval based on median PFS by blinded independent central review (BICR) as a primary endpoint.

Patients enrolled in Phase 2 at the selected dose would continue on treatment and be included in the Phase 3 study analysis, supplemented by enrollment of approximately 120 additional patients into the Phase 3 portion of the clinical trial with 2:1 randomization on the same basis as the Phase 2 portion. Efficacy data from the Phase 3 could support potential approval using median OS as a primary endpoint.

Clinical Data Update – Darovasertib in (Neo)Adjuvant Primary UM

The company observed further evidence of encouraging clinical activity for darovasertib as neoadjuvant therapy in primary uveal melanoma (UM), including responses in primary ocular tumor lesions. Data was reported from an ongoing investigator sponsored trial (IST) evaluating darovasertib in (neo)adjuvant uveal melanoma, from compassionate use protocol(s) and from the company’s Phase 1/2 clinical trial evaluating darovasertib as monotherapy and in combination with crizotinib. Best ocular tumor response is reported based on maximal percentage reduction in measured apical height or longest basal diameter.

Collectively, these data further substantiate clinical proof of concept (PoC) for the use of darovasertib in the (neo)adjuvant uveal melanoma setting:

Ocular tumor shrinkage by investigator review in 9 of 9 (100%) UM (n=6) or MUM (n=3) patients treated as monotherapy or in combination with crizotinib, including a neoadjuvant UM patient treated with darovasertib with a partial response at 1 month, and a second neoadjuvant UM patient treated with the darovasertib and crizotinib combination with ~80% ocular tumor shrinkage at 4 months who was spared enucleation, as described below.
A UM patient who was already blind in one eye from vascular disease developed a large uveal melanoma lesion in his other eye and sought neoadjuvant treatment with a goal to avoid enucleation and potentially preserve vision in the affected eye to prevent blindness. This patient, who remains on therapy, was treated with darovasertib and crizotinib combination under a compassionate use protocol. The preliminary clinical data showed:
observed ~80% ocular tumor shrinkage after 4 months of treatment and remains on therapy
avoided enucleation of the affected eye, which we believe to be a first reported case of systemic neoadjuvant therapy resulting in eye preservation
prompt responsiveness to treatment, including progressive tumor shrinkage, as determined by investigator measurement of tumor apical height, over each month of treatment, including approximately 30% ocular tumor shrinkage after 1 month, with ocular lesion size reduced to approach threshold for plaque brachytherapy, and further ocular tumor shrinkage to ~50% after 2 months, ~70% after 3 months and ~80% after 4 months of treatment
improved vision following course of treatment and treatment of a severe cataract: pretreatment vision score was 6/120, where 6/60 is legally blind; post-treatment vision score was 6/5, reflecting a greater than 20-fold improvement and resulting in better than normal vision. Vision scoring was based on AU meter measurement system: 6/6 m = 20/20 ft (normal vision).
"These additional clinical data underscore the potential for darovasertib as a (neo)adjuvant approach for the treatment of uveal melanoma patients. If clinically validated, this approach could significantly improve current primary treatment paradigms, which typically include radiotherapies and/or enucleation of the eye," said Prof. Anthony Joshua, MBBS Ph.D. FRACP, Head of the Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent’s Hospital/Garvan Medical Research Institute, Sydney, Australia.

IDEAYA is initiating a company-sponsored clinical trial to evaluate darovasertib as monotherapy in (neo)adjuvant uveal melanoma and is evaluating potential near-term clinical neoadjuvant endpoints such as organ preservation (avoiding enucleation) for large ocular tumors and reduction in radiation dose and/or vision preservation for small or medium ocular tumors.

IDEAYA is also supporting St. Vincent’s Hospital Sydney Limited, which has initiated an ongoing IST captioned as "Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM) (NCT05187884), to evaluate darovasertib monotherapy in a neoadjuvant and adjuvant setting in primary UM patients.

Addressable Patient Population in MUM and UM

The potentially addressable patient population for metastatic uveal melanoma is estimated to include approximately 4,500 patients across U.S. and Europe, based on estimated annual incidence, and approximately 14,000 patients in total prevalence in the US and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib – with a potential annual incidence of approximately 8,700 patients aggregate in U.S. and Europe, and approximately 100,000 patients in total prevalence in the U.S. and Europe.

IDEAYA owns or controls all commercial rights in darovasertib, including in MUM and in UM, subject to certain economic obligations pursuant to the Novartis exclusive, worldwide license.

IDEAYA Investor Webcast and Conference Call

IDEAYA will host an investor webcast and conference tomorrow morning, Monday, April 24, 2023 at 8:00 am Eastern Time (ET), to present the further darovasertib and crizotinib Phase 2 clinical efficacy and tolerability data in metastatic uveal melanoma, and the potential registrational clinical trial design based on guidance and feedback from the recent FDA Type C meeting. The company will also provide a clinical data update for darovasertib in neoadjuvant uveal melanoma.

Presenters at the investor webcast and conference call will include Dr. Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, Prof. Anthony Joshua, MBBS Ph.D. FRACP, Head of the Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent’s Hospital/Garvan Medical Research Institute, Sydney, Australia, and Prof. Mark Shackleton, MBBS, Ph.D., FRACP, Professor of Oncology, Monash University, Director of Oncology, Alfred Health, Chair, Melanoma and Skin Cancer Trials, Melbourne, Australia, each of whom are key opinion leaders and clinical investigators. Yujiro S. Hata, Chief Executive Officer of IDEAYA Biosciences, and Darrin Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA Biosciences, will also present.

IDEAYA’s darovasertib investor webcast presentation, as well as an updated corporate presentation, which incorporates the updated darovasertib clinical data as well as IDE397, IDE161 and Werner Helicase program updates from AACR (Free AACR Whitepaper) 2023, will be available on the company’s website, at its Investor Relations portal (View Source) in advance of the investor webcast presentation at approximately 6:00 am ET.

Corporate Updates
IDEAYA had cash, cash equivalents and marketable securities of approximately $373 million as of December 31, 2022, which it currently projects will be sufficient to fund its planned operations into 2026.

On April 23, 2023 Singapore based SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, reported that late-breaking data from the company’s TCR-T therapy pipeline – SCG101, will be presented at the International Society for Cell & Gene Therapy (ISCT) in Paris, France on 1 June (Press release, SCG Cell Therapy, APR 23, 2023, View Source;gene-therapy-isct-highlighting-promising-antitumor-and-antiviral-activities-of-scg101-in-treating-hbv-related-hepatocellular-carcinoma-301804926.html [SID1234630399]).

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"These exciting new data being presented at ISCT continue to reinforce the potential for viral antigen specific TCR-T product to effectively treat infection-associated solid tumour indications like HBV-related hepatocellular carcinoma," said Frank Wang, Chief Executive Officer of SCG Cell Therapy. "The clinical data shows exceptional efficacy of this novel TCR-T cell therapy. Thus far, SCG101 has shown to produce robust and durable anti-tumour and antiviral responses and we look forward to providing additional updates on this program as the trial progresses."

SCG101 is an autologous TCR-T cell therapy targeting specific hepatitis B surface antigen (HBsAg) epitopes. The late-breaking data to be presented at ISCT demonstrated positive efficacy of SCG101 as a monotherapy in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), achieving partial response (PR) after a single dose of SCG101 with durable tumour response observed. Serum HBsAg significantly decreased and the expression of HBsAg in hepatocyte dropped to undetectable.

In June 2022, SCG Cell Therapy presented the first clinical proof-of-concept data demonstrating the mechanism of action of a HBsAg-specific TCR-T cell therapy, SCG101, at the International Liver Congress (ILC) 2022. The data showed precise target engagement and cell proliferation, and demonstrated antiviral activity and tumour control. Sixty-six percent of patients with advanced HBV-related HCC observed lesion shrinkage as well as significant serum HBsAg reduction (> 2 log) within 28 days from single dose monotherapy SCG101 treatment.

Presentation Details:
Title: Infected hepatocyte clearance and sustained tumour regression by first-in-class HBsAg-specific TCR-T (SCG101) therapy for HBV-related HCC
Presenter: 1093
Abstract Number: 3907176
Date and Time: 1 June, 2023

About SCG101
SCG101, an autologous T-cell receptor (TCR) T cell therapy, is an investigational cell therapy product targeting specific epitopes of hepatitis B surface antigen (HBsAg). Utilizing SCG’s proprietary GianTTM technology, high affinity and high avidity natural TCR can be identified against intracellular antigens expressed through major histocompatibility complex (MHC) in solid tumours. Preclinical studies of SCG101 demonstrated tumour inhibition and HBV cccDNA eradication. SCG101 was granted clinical trial approvals by the U.S Food and Drug Administration (FDA), China National Medical Products Administration (NMPA) and Singapore Health Science Authority (HSA) for patient with HBV-related HCC. A Phase 1/2 clinical trial evaluating SCG101 is ongoing.

About Hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It is estimated more than 905,000 new cases of liver cancer and more than 830,100 deaths from the disease globally in 2020, making it one of the leading causes of cancer deaths around the world [1]. Chronic hepatitis B virus (HBV) infection accounts for at least 50% of cases of HCC worldwide [2]. HCC is typically diagnosed at an advanced stage and is associated with a poor prognosis. The five-year survival rate of less than 15%.

On April 23, 2023 Bridge Biotherapeutics (KQ288330), a clinical-stage biotech company based in South Korea and Cambridge that is advancing novel drugs for cancer, fibrosis, and inflammation, reported that it received notice from the U.S. Food and Drug Administration (FDA) that it may proceed with the first-in-human study of BBT-207, which has the potential to be a mutant selective and broad-spectrum fourth-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) for the treatment of non-small cell lung cancer (NSCLC) (Press release, Bridge Biotherapeutics, APR 23, 2023, View Source [SID1234630398]). (US IND Number: IND 165492)

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The company recently disclosed up-to-date preclinical data for BBT-207 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 annual meeting. According to the poster presentation, the company highlighted the intracranial antitumor activity as well as the antitumor efficacy of the experimental drug through in vitro and in vivo studies. Overall, the company explored potent activity and efficacy against a broad range of EGFR mutations in NSCLC, including C797S double mutations, which arise after third-generation EGFR TKI treatment.

"We’re excited to initiate the clinical development of BBT-207 in order to address the unmet medical needs of NSCLC patients," said James Lee, founder and CEO of Bridge Biotherapeutics. "With this approval, the company will continue to focus on developing novel treatment options for late-stage lung cancer patients suffering from third-generation EGFR TKI resistance."

The first-in-human study of BBT-207 consists of three phases. Bridge plans to initiate a dose escalation study during phase 1a to determine the Recommended Dose Range (RDR) based on the toxicity/tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of the experimental drug. Also, phase 1a aims to observe safety and tolerability of BBT-207 based on treatment-emergent adverse events (AEs), etc. Through phase 1b, the company will select the recommended phase 2 dose (RP2D) based on PK, PD, objective response rate (ORR), duration of response (DOR), and the overall safety profile. Finally, during the dose expansion study, phase 2 preliminary antitumor activity of BBT-207 will be evaluated based on RECIST Version 1.1.

The multi-centered study is expected to include approximately 15 clinical sites in the United States and South Korea, targeting up to 92 patient participants.

STUDY TITLE: First-in-Human Study of BBT-207 in Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutation After Treatment with EGFR TKI
STUDY DESIGN: An open-label, Phase 1/2 study evaluating safety, tolerability, PK, PD, and preliminary antitumor activity of BBT-207 in patients with advanced NSCLC harboring EGFR mutation after treatment with EGFR TKI. The study will consist of 3 parts; dose escalation, recommended phase 2 dose selection, and dose expansion phases
TEST PRODUCT: Oral administration of BBT-207 throughout a 21-day cycle for each phase
STUDY OBJECTIVES: To evaluate the safety, tolerability, PK, PD, and preliminary efficacy (antitumor activity) of BBT-207 in patients with advanced NSCLC harboring EGFR mutation after treatment with EGFR TKI

On April 21, 2023 Fosun reported that according to the public announcement made by the Centre for Drug Evaluation of National Medical Products Administration (the "NMPA"), the FCN-159 tablets (the "Investigational New Drug") of Shanghai Fosun Pharmaceutical Industrial Development Company Limited (the "Company" and, together with its subsidiaries/units, the "Group", the same applies below), have been granted breakthrough therapy designation for the treatment of histiocytic tumors (Filing, Fosun, APR 21, 2023, View Source [SID1234633490]).

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II. Basic Information and Research Progress of the Investigational New Drug
The Investigational New Drug is an innovative small molecule chemical drug self-developed by the Group , which is a MEK1/2 selective inhibitor and is intended to be used primarily for the treatment of advanced solid tumors, type I neurofibromas, histiocytic tumors and arteriovenous malformations

As at the date of this announcement, the Investigational New Drug is at the stage of Phase I clinical trial in China (excluding Hong Kong, Macau and Taiwan region for the purpose of this announcement, the same applies below) for the treatment of malignant melanoma; the Investigational New Drug is at the stage of Phase II clinical trials in China, the United States and Europe for the treatment of type I neurofibroma; and the Investigational New Drug is at the stage of Phase II clinical trials in China for the treatment of histiocytic tumors, low-grade glioma and arteriovenous malformations respectively. The application for Phase II clinical trial of the Investigational New Drug for childhood Langerhans cell histiocytosis/Langerhans cell histiocytic hyperplasia has also been approved by the NMPA.

As at the date of this announcement, the MEK1/2 selective inhibitor approved for launch in China include MEGININE (邁吉寧 ) (Trametinib Tablets) of Novartis Europharm Limited. According to the data from IQVIA CHPA (provided by IQVIA, a professional information and strategic consulting service provider for the pharmaceutical and health industry, IQVIA CHPA data represents the drug sales market of hospitals with over 100 beds in China. The actual sales of different drugs may differ from the IQVIA CHPA data to varying degrees due to their different sales distribution channels), the sales of MEK1/2 selective inhibitor in China amounted to approximately RMB98.68 million in 2022. As of March 2023, the Group has invested approximately RMB 311.95 million (unaudited) in total in the research and development ("R&D") of the Investigational New Drug at this stage.

III. Risk Reminder
As required by the relevant laws and regulations in China, the Investigational New Drug is subject to undergo a series of clinical studies and approval by the relevant national drug review department in China before it can be launched. There are certain risks in the R&D of new drugs based on our experience. For example, clinical trials may be terminated due to issues such as safety and/or efficacy.