On September 9, 2024 Astrazeneca reported detailed results from the TROPION-Lung01 Phase III trial showed a clinically meaningful trend toward improving overall survival (OS) with datopotamab deruxtecan (Dato-DXd) compared to docetaxel, the current standard of care chemotherapy, in adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy (Press release, AstraZeneca, SEP 9, 2024, View Source [SID1234646447]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These results will be presented today during an oral presentation (OA08.03) at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

In the overall trial population, OS results numerically favoured datopotamab deruxtecan compared to docetaxel (12.9 versus 11.8 months) but did not reach statistical significance (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.78-1.14; p=0.530). In the prespecified subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan showed a 2.3-month improvement in OS compared to docetaxel (14.6 versus 12.3 months; HR 0.84; 95% CI 0.68-1.05). In patients with nonsquamous NSCLC, OS improvement was observed regardless of the presence of actionable genomic alterations. In patients with squamous NSCLC, consistent with the previous analysis, datopotamab deruxtecan did not show an OS improvement.

Jacob Sands, MD, Dana-Farber Cancer Institute, Medical Oncology and investigator in the trial, said: "Despite many efforts to surpass docetaxel with novel approaches in previously treated advanced or metastatic non-small cell lung cancer, patients only survive for about one year. For datopotamab deruxtecan to show a statistically significant improvement in progression-free survival along with improved response rate, duration of response and an overall survival improvement numerically consistent with progression-free survival is clinically meaningful for patients with nonsquamous lung cancer."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "TROPION-Lung01 showed a clinically meaningful trend towards improving the survival of patients with advanced or metastatic nonsquamous non-small cell lung cancer, building on the previously reported progression-free survival data. Together with the data we have presented for the potential TROP2-QCS biomarker and from NeoCOAST-2 in early-stage disease, these results underscore our confidence in the important role datopotamab deruxtecan can play across segments and settings of non-small cell lung cancer."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "For patients with nonsquamous non-small cell lung cancer, disease progression is common, making this patient population difficult to treat. The data from TROPION-Lung01 demonstrate the potential of datopotamab deruxtecan in this setting and support our comprehensive development programme where we are also evaluating this TROP2-directed antibody drug conjugate as part of combination strategies in earlier treatment settings of non-small cell lung cancer."

The safety profile of datopotamab deruxtecan in TROPION-Lung01 was consistent with the previous analysis including lower rates of dose reduction (20%, 30%) and discontinuation (8%, 12%) due to adverse events compared to docetaxel. The median treatment duration for datopotamab deruxtecan was 4.2 months versus 2.8 months for docetaxel. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 26% and 42% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (1%, 23%), leukopenia (0%, 13%), stomatitis (7%, 1%), anemia (4%, 4%), interstitial lung disease (ILD) (4%, 1 %) and asthenia (3%, 2%). No new ILD events of any grade were adjudicated as drug-related since the previous analysis.

In TROPION-Lung01, patient enrollment by tumour histology was balanced across treatment arms and consistent with real-world incidence with approximately 75% of enrolled patients having nonsquamous NSCLC.1,2 In both arms, 17% of patients had tumours expressing actionable genomic alterations, such as epidermal growth factor receptor (EGFR) mutations.

This final analysis of OS builds on the positive progression-free survival (PFS) results presented at the 2023 European Society for Medical Oncology Congress, which showed datopotamab deruxtecan demonstrated a statistically significant improvement in PFS in the overall trial population and a clinically meaningful PFS benefit in patients with nonsquamous NSCLC. The OS data have been shared with health authorities currently reviewing applications for this indication.

Summary of TROPION-Lung01 survival results

Overall trial population

Datopotamab deruxtecan (n=299)

Docetaxel

(n=305)

Median OS (95% CI)i

12.9 months (11.0-13.9)

11.8 months (10.0-12.8)

HR (95% CI)

0.94 (0.78-1.14)

p-value

0.530

Pre-specified boundary (2-sided)

0.045

Nonsquamous histology

Datopotamab deruxtecan (n=234)

Docetaxel

(n=234)

Median OS (95% CI)i

14.6 months (12.4-16.0)

12.3 months (10.7-14.0)

HR (95% CI)

0.84 (0.68-1.05)

OS probability at 12 months (95% CI)

58.8% (52.0-64.9)

52.8% (45.9-59.2)

OS probability at 24 months (95% CI)

29.0% (22.8-35.5)

21.7% (16.0-28.0)

Nonsquamous histology – with actionable genomic alterations

Datopotamab deruxtecan (n=48)

Docetaxel

(n=50)

Median OS (95% CI)i

15.6 months

9.8 months

HR (95% CI)

0.65 (0.40-1.08)

Nonsquamous histology – without actionable genomic alterations

Datopotamab deruxtecan (n=186)

Docetaxel

(n=184)

Median OS (95% CI)i

13.6 months

12.3 months

HR (95% CI)

0.89 (0.70-1.13)

CI, confidence interval; HR, hazard ratio; OS, overall survival
iMedian follow-up was 23.1 months for both the datopotamab deruxtecan and docetaxel arms

Datopotamab deruxtecan plus Imfinzi and chemotherapy showed promising response rates in patients with early-stage resectable NSCLC

Results from the NeoCOAST-2 Phase II platform trial evaluating Imfinzi (durvalumab) in multiple novel combinations, before and after surgery, in patients with early-stage (Stage IIA-IIIB) resectable NSCLC were featured in a WCLC Presidential Symposium (PL02.07). Preliminary results from the trial arm testing neoadjuvant Imfinzi plus datopotamab deruxtecan and carboplatin demonstrated a pathological complete response (pCR) rate of 34.1% (95% CI 20.5-49.9) and a major pathological response (mPR) rate of 65.9% (95% CI 50.1-79.5). This was numerically higher than the response rates shown by other combination regimens tested, however, the trial was not powered to make direct statistical comparisons between arms.

The safety profile of Imfinzi plus datopotamab deruxtecan and carboplatin was consistent with the known safety profiles of these agents. Surgical rates across arms were comparable and in line with those shown in recent Phase III trials. AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan in combination with Imfinzi in multiple ongoing trials.

Also featured in a WCLC Presidential Symposium were results from an exploratory analysis of TROPION-Lung01 which showed TROP2 as measured by AstraZeneca’s proprietary computational pathology platform, quantitative continuous scoring (QCS), was predictive of clinical outcomes in patients with advanced or metastatic NSCLC treated with datopotamab deruxtecan.

Notes

Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 NSCLC is the most common type of lung cancer, accounting for about 80% of cases.2 Approximately 75% and 25% of NSCLC tumours are of nonsquamous or squamous histology, respectively.3 While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy.4-6 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.4-6

TROP2 is a protein broadly expressed in the majority of NSCLC tumours.7 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.8,9

TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m2) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate (ORR), duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

NeoCOAST-2
NeoCOAST-2 is a global, randomised, multicentre, open-label, multi-arm Phase II platform trial evaluating the efficacy and safety of Imfinzi in multiple novel combinations, before and after surgery, in patients with resectable, early-stage (Stage II-IIIB) NSCLC.

The dual primary endpoints of NeoCOAST-2 are antitumour activity of neoadjuvant treatment assessed by pCR and the safety and tolerability of neoadjuvant and adjuvant treatment. Key secondary endpoints include event-free survival, disease-free survival and ORR as assessed by both RECIST version 1.1 and investigator, OS, tumour resection and mPR as defined by central blinded independent pathologist review.

NeoCOAST-2 will enrol approximately 490 patients in Asia, Europe and North America. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.

On September 9, 2024 NiKang Therapeutics Inc. ("NiKang"), a clinical-stage biotech company focused on developing innovative small molecule oncology medicines to bring transformative therapies to patients in need, reported that preliminary data from its ongoing Phase 1/2 clinical trial evaluating NKT2152 for the treatment of previously treated advanced clear cell renal cell carcinoma (ccRCC) will be presented in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 Congress on September 13, 2024, in Barcelona, Spain (Press release, NiKang Therapeutics, SEP 9, 2024, View Source [SID1234646463]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This oral presentation marks an important milestone in the clinical development of NKT2152, a highly selective, potent and orally available HIF2α inhibitor with a potential best-in-class profile. The findings strengthen our belief that deep inhibition of HIF2α can lead to meaningful clinical benefits in patients at dose levels that are generally well tolerated," said Zhenhai Gao, Ph.D., co-founder, president and CEO of NiKang. "These data demonstrate NKT2152’s robust anti-tumor activity in heavily pretreated, high risk advanced ccRCC patients. They also support the hypothesis that NKT2152’s potency and improved systemic exposure have the potential to enhance the current standard of care."

Details for the presentation are as follows:

Presentation Title: NKT2152, a novel oral HIF2α inhibitor, in participants (pts) with previously treated advanced clear cell renal cell carcinoma (accRCC): Preliminary results of a Phase 1/2 study
Session Title: Proffered paper session 1: GU tumors, non-prostate
Session Date and Time: Friday, September 13, from 14:00 – 15:30 CET (8:00 – 9:30am ET)
Presentation Number: 1690O
Presenter: Eric Jonasch, MD (MD Anderson Cancer Center, Houston, TX)
Location: Santander Auditorium – Hall 5

After the oral presentation, the full presentation will be available at Science & Pipeline – NiKang Therapeutics (www.nikangtx.com).

About NKT2152

NKT2152 is a potent, selective and orally available small molecule HIF2α inhibitor which binds to HIF2α allosterically and disrupts the HIF2α/HIF1β transcription factor complex, thereby reducing the production of proteins which lead to tumorigenesis. NKT2152 is currently under evaluation in a Phase 1/2 clinical study in ccRCC as a single agent (NCT05119335) and a Phase 2 clinical study in ccRCC in combination with palbociclib and sasanlimab (NCT05935748). A third clinical study, sponsored by F. Hoffman-La Roche Ltd., evaluating the combination with standard-of-care atezolizumab (Tecentriq) and bevacizumab (Avastin) in first-line unresectable/advance hepatocellular carcinoma (HCC) (NCT04524871) is planned.

On September 9, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that new and updated data from several studies of compounds discovered by HUTCHMED will be presented at the 2024 World Conference on Lung Cancer ("WCLC24") in San Diego, USA, and the European Society for Medical Oncology ("ESMO") Congress 2024, taking place in Barcelona, Spain (Press release, Hutchison China MediTech, SEP 9, 2024, View Source [SID1234646432]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Results from the FLOWERS study, a prospective, two-arm, randomized, multicenter Phase II clinical trial of osimertinib with or without savolitinib as first-line treatment in EGFRm, MET-aberrant advanced non-small cell lung cancer ("NSCLC") patients, will be presented at WCLC24. As of May 28, 2024, the median follow-up was 8.2 months. Patients treated with osimertinib plus savolitinib (Cohort 2, N=21) showed deeper and more durable response over osimertinib monotherapy (Cohort 1, N=23) along the study follow-up. The confirmed objective response rate (ORR) in Cohort 1 and Cohort 2 were 60.9% and 90.5%, respectively, with disease control rate (DCR) of 87% and 95.2%, respectively. Immature progression-free survival ("PFS") data also showed a positive trend in favor of the combination therapy, with median PFS of 9.3 months and 19.6 months in the cohort 1 and cohort 2 with maturity of 34.8% and 23.8%, respectively. Safety profiles of osimertinib monotherapy and osimertinib plus savolitinib were as expected, tolerable and manageable.

Abstract title Presenter / Lead author Presentation details

WCLC24 – INVESTIGATOR-INITIATED STUDIES

Osimertinib with or without savolitinib as 1L in de novo MET aberrant, EGFRm advanced NSCLC (CTONG 2008): A Phase II trial Jinji Yang,
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, China PL04.10
Plenary Session
PL04 Presidential Symposium 2,Plenary Hall
Monday, September 9, 2024 at 8:30 AM PDT
Study of Surufatinib Combined with Low Dose Topotecan in Second or Third-Line Multiple Distant Organ Metastatic ES-SCLC Yingying Du, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Hesheng Qian, Fuyang Cancer Hospital, Fuyang, China EP.13A.04A
ePoster
Saturday, September 7, 2024
Surufatinib Plus Docetaxel in Patients with Relapsed Advanced Driver-Negative Non-Squamous NSCLC: A Phase Ib/II Study Qitao Yu, Wei Jiang,
Guangxi Medical University Cancer Hospital, Nanning, China P3.12C.08
Poster
Monday, September 9, 2024 at 8:30 AM PDT

Further analysis of fruquintinib’s FRESCO-2 study in metastatic colorectal cancer and FRUTIGA study in gastric cancer, a biomarker study of savolitinib in gastric cancer as well as investigator-initiated studies of fruquintinib and surufatinib will be presented at the ESMO (Free ESMO Whitepaper) Congress 2024. Details of the presentations are as follows:

Abstract title Presenter / Lead author Presentation details
ESMO 2024 – SPONSORED STUDIES
Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer with and without liver metastasis: A subgroup analysis of the phase 3 FRESCO-2 trial Rocio Garcia-Carbonero,
Hospital Universitario 12 de Octubre, lmas12, UCM, Madrid, Spain 520P
Poster Session – Colorectal cancer
Monday, 16 September 2024
Efficacy and safety of fruquintinib in refractory metastatic colorectal cancer: A FRESCO-2 subgroup analysis by age Maria Elena Elez Fernandez,
Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain 526P
Poster Session – Colorectal cancer
Monday, 16 September 2024
Efficacy of fruquintinib plus paclitaxel (F+PTX) in patients (pts) with prior immunotherapy (prior-IO): subgroup analysis from FRUTIGA study Lin Shen,
Peking University Cancer Hospital & Institute, Beijing, China 1410P
Poster Session – Oesophagogastric cancer
Monday, 16 September 2024
Impact of subsequent anti-tumor therapies in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma receiving fruquintinib (F) plus paclitaxel (PTX) or placebo plus PTX in FRUTIGA study Ruihua Xu,
Sun Yat-sen University Cancer Center, Guangzhou, China 1434P
Poster Session – Oesophagogastric cancer
Monday, 16 September 2024
Association between Fruquintinib-induced Hypertension and Clinical Outcomes from FRUTIGA, a Phase 3 Study of Fruquintinib plus Paclitaxel in Previously Treated Advanced Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma Shukui Qin,
Chinese People’s Liberation Army Cancer Center of Nanjing Bayi Hospital, Nanjing, China 1443P
Poster Session – Oesophagogastric cancer
Monday, 16 September 2024
Analysis of MET gene alterations in cfDNA samples from a phase II study of savolitinib in patients (pts) with MET-amplified gastroesophageal junction adenocarcinomas or gastric cancer (GEJ/GC) Zhi Peng,
Peking University Cancer Hospital & Institute, Beijing, China 1461P
Poster Session – Oesophagogastric cancer
Monday, 16 September 2024
ESMO 2024 – INVESTIGATOR-INITIATED STUDIES
A phase II clinical study of fruquintinib (Fru) combined with toripalimab (Tor) and short-course radiotherapy (SCRT) as neoadjuvant therapy for locally advanced rectal cancer (LARC) Zhiping Li, Ye Chen,
West China Hospital of Sichuan University, Chengdu, China 570P
Poster Session – Colorectal cancer
Monday, 16 September 2024
Stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer: Updated findings from a single-arm, prospective phase II trial (RIFLE) Zhen Zhang, Yajie Chen,
Fudan University Shanghai Cancer Center, Shanghai, China 537P
Poster Session – Colorectal cancer
Monday, 16 September 2024
Fruquintinib combined with sintilimab and chemotherapy as the first-line treatment in advanced naïve EGFR- and ALK-negative non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results Yongqian Shu, Pei Ma,
Jiangsu Province Hospital/The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 1329P
Poster Session – NSCLC, metastatic
Saturday, 14 September 2024
Fruquintinib in combination with sintilimab and CAPEOX as first-line treatment for advanced G/GEJ cancer: A phase 1b/2 clinical trial (FUNCTION) Xiaobing Chen, Beibei Chen,
Henan Cancer Hospital/ Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China 1475TiP
Poster Session – Oesophagogastric cancer
Monday, 16 September 2024
Fruquintinib combined with nab-paclitaxel and gemcitabine (AG) as the first-line treatment for pancreatic ductal adenocarcinoma (PDAC) with liver metastases: An open-label, single-arm, single-center phase II clinical study Xianjun Yu, Miaoyan Wei,
Fudan University Shanghai Cancer Center, Shanghai, China 1529P
Poster Session – Pancreatic cancer
Monday, 16 September 2024
A phase II study of Fruquintinib in the 1L or 2L treatment of unresectable metastatic soft tissue sarcoma Zhiguo Luo, Xiaowei Zhang,
Fudan University Shanghai Cancer Center, Shanghai, China 1743P
Poster Session – Sarcoma
Saturday, 14 September 2024
Surufatinib combined with anti-PD-1/PD-L1 antibody in the second line or monotherapy in third line treatment of advanced hepatocellular carcinoma: A single-arm, open-label, multi-center phase II study Fuxiang Zhou,
Zhongnan Hospital, Wuhan University, Wuhan, China 974P
Poster Session – Hepatocellular carcinoma (HCC)
Monday, 16 September 2024
Updated results of Surufatinib plus transarterial embolization versus surufatinib monotherapy in neuroendocrine tumor with liver metastasis: a prospective, randomized, controlled trial Dan Cao,
West China Hospital, Sichuan University, Chengdu, China 1155P
Poster Session – Neuroendocrine tumours
Monday, 16 September 2024
Surufatinib plus toripalimab combined with pemetrexed (A), and platinum (P) in patients (pts) with advanced non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results of a single-center, phase II trial Li Zhang, Wenfeng Fang,
Sun Yat-Sen University Cancer Center, Guangzhou, China 1345P
Poster Session – NSCLC, metastatic
Saturday, 14 September 2024
Surufatinib combined with gemcitabine in soft tissue sarcoma (STS) patients failed with anthracyclines chemotherapy or monotherapy post-anlotinib progression: a multi-center, phase II trial Xiaohui Niu, Yuhong Zhou,
Zhongshan Hospital, Fudan University, Shanghai, China 1740P
Poster Session – Sarcoma
Saturday, 14 September 2024

On September 9, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported an oral presentation of updated results from a pivotal Phase 2 clinical trial of Dupert（fulzerasib）for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation at the 2024 World Conference on Lung Cancer (WCLC) (Press release, Innovent Biologics, SEP 9, 2024, View Source [SID1234646448]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Fulzerasib is a novel, orally active, potent KRAS G12C inhibitor. Based on the results from this single-arm registrational Phase 2 clinical study (NCT05005234).

Dupert (fulzerasib) received approval by the NMPA in August 2024 for the treatment of adult patients with advanced NSCLC harboring the KRAS G12C mutation who have received at least one systemic therapy.

As of the data cutoff date (Dec 13, 2023), a total of 116 NSCLC subjects were enrolled and evaluable.

Fulzerasib showed encouraging antitumor activity. The confirmed objective response rate (ORR) assessed by the Independent Radiology Review Committee (IRRC) was 49.1% (95% CI: 39.7-58.6). The disease control rate (DCR) was 90.5% (95%CI: 83.7, 95.2). The median duration of response (DoR) has not yet been reached, while the median progression-free survival (PFS) was 9.7 months (95%CI: 5.6-11.0). Median overall survival (OS) has not been reached.
Fulzerasib was generally well-tolerated, with no additional safety signals observed. Treatment-related adverse events (TRAEs) occurred in 92.2% of patients (107 individuals), mostly Grade 1-2. The most common TRAEs included anemia, increased alanine aminotransferase, increased aspartate aminotransferase, asthenia and proteinuria.
Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, stated: "As a potent KRAS G12C inhibitor, Dupert monotherapy has demonstrated encouraging efficacy in advanced lung cancer with KRAS G12C mutations, with the pivotal registry study meeting the prespecified primary endpoints and overall favorable safety profile. As the first KRAS G12C inhibitor approved in China, Dupert provides a new treatment option for cancer patients harboring this gene mutation in China. We look forward to seeing more KRAS G12C-mutated patients with advanced lung cancer benefit from this drug soon."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to share the latest clinical data from the registration study of Dupert at the WCLC. Thanks to the exceptional efficacy and good tolerability demonstrated in this study, Dupert was recently approved as the first KRAS G12C inhibitor in China. Moving forward, we remain committed to advancing Dupert as both a monotherapy and in combination treatments, aiming to maximize the clinical value of this innovative targeted drug and benefit more patients."

About Dupert (Fulzerasib, KRAS G12C Inhibitor)

The RAS protein family is categorized into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancers, 30-40% of colon cancers, and 15-20% lung cancers. The KRAS G12C mutation is more prevalent than the combined occurrence of ALK, ROS1, RET and NTRK 1/2/3 mutations.

Fulzerasib is a novel, orally active and potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange—an essential step in pathway activation—by covalently and irreversibly modifying the cysteine residue of KRAS G12C protein. Preclinical cysteine selectivity studies demonstrated high selectivity of fulzerasib towards G12C, leading to inhibition of downstream signaling, resulting in tumor cells apoptosis and cell cycle arrest.

In September 2021, Innovent and GenFleet Therapeutics entered an exclusive license agreement for the development and commercialization of fulzerasib (Innovent R&D code: IBI351, GenFleet R&D code: GFH925) in China, including mainland China, Hong Kong, Macau and Taiwan.

In January 2023, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) granted Breakthrough Therapy Designation (BTD) to fulzerasib for the treatment of patients with advanced NSCLC harboring KRAS G12C mutation who have received at least one prior systemic therapy. In May 2023, another BTD was granted for the treatment of advanced CRC patients with KRAS G12C mutation who had undergone at least two systemic therapies.

As of August 2024, the CDE of NMPA has approved fulzerasib for the treatment of adult patients with advanced NSCLC harboring the KRAS G12C mutation who have received at least one systemic therapy.

On September 9, 2024 Candid Therapeutics, Inc. ("Candid"), a biotechnology company dedicated to developing potentially transformative drugs to address autoimmune diseases, reported its official launch today (Press release, Candid Therapeutics, SEP 9, 2024, View Source [SID1234646464]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Recent groundbreaking clinical data has showcased the pivotal role of a specific subset of immune cells, B lymphocytes, in autoimmune diseases. B lymphocytes lead to autoimmune pathology by producing autoantibodies that attack the body’s own tissues and also through antigen presentation and cytokine release. Selective depletion of B lymphocytes has shown unprecedented clinical efficacy in highly refractory patients across multiple autoimmune diseases such as rheumatoid arthritis and myasthenia gravis. Candid is developing T-cell engager ("TCE") antibodies that can deplete specific B lymphocyte cell populations and aims to be the first company to bring these novel therapies to market.

To accelerate development of and position Candid to become the leader in TCE antibodies for autoimmune diseases, Candid acquired Vignette Bio and TRC 2004 through a simultaneous three-way merger and multi-step financing. This acquisition integrates two cutting-edge bispecific TCEs:

CND106, a BCMAxCD3 bispecific antibody from Vignette Bio, which was initially founded by Foresite Labs who exclusively licensed ex-China rights for the drug candidate from EpimAb Biotherapeutics.
CND261, a CD20xCD3 bispecific antibody from TRC 2004, which was established through a collaboration between Two River and Third Rock Ventures who exclusively licensed ex-China rights for the drug candidate from Genor Biopharma.
CND106 and CND261 have both completed Phase 1 dose escalation studies with combined data in over 130 oncology patients. Both drug candidates have shown potential to become best-in-class therapies for various autoimmune diseases.
The founding Candid team includes an accomplished set of seasoned entrepreneurs who have repeatedly advanced nascent ideas into late-stage development products and commercialization.

Ken Song, MD as Chairman, President and CEO has successfully led several life science companies with over $5.5 billion in realized shareholder value. Most recently he led RayzeBio, a radiopharmaceutical company, from concept to Phase 3 in just over 3 years and negotiated a $4.1 billion sale of the company earlier this year to Bristol Myers Squibb.
Timothy Lu, MD, PhD as Chief Medical and Scientific Officer was instrumental in the clinical development of novel oral IL-17 drugs for autoimmune diseases at DICE Therapeutics which was acquired last year by Eli Lilly, where he stayed on until joining the Candid team.
Bernie Huyghe, PhD as Chief Technology Officer has over 30 years of experience in manufacturing of biologics and other complex therapeutic products and prior to Candid, was overseeing two Phase 3 antibody programs at Viridian Therapeutics.
Arvind Kush as Chief Financial and Business Officer has had an illustrious career first as a managing director in healthcare banking at Bank of America before transitioning to RayzeBio as CFO where he navigated a highly successful oversubscribed IPO in September 2023.
In conjunction with the merger, Candid has successfully raised over $370 million in capital from an extensive roster of investors, which includes a recently completed financing co-led by Venrock Healthcare Capital Partners, Fairmount, TCGX, and venBio Partners. Other notable healthcare investors supporting the company include Foresite Capital, Third Rock Ventures, Fidelity Management & Research Company, Samsara BioCapital, Qiming Venture Partners USA, OrbiMed, Boxer Capital, Redmile Group, Vida Ventures, Two River, Franklin Templeton, LifeSci Venture Partners, Mirae Asset Capital Life Science, Polaris Innovation Fund, Soleus Capital and other reputable institutional and mutual fund investors. This substantial financial backing highlights strong investor confidence in Candid’s purposeful approach and strategic vision, positioning the company for significant impact in bringing forth first-in-class therapies to patients with autoimmune diseases.

"TCE antibodies have the most promise as scalable and patient friendly drugs to deplete B cells for treatment of a myriad of autoimmune conditions and represents a once in a generation development opportunity," said Dr. Ken Song, Chairman, President, and CEO of Candid Therapeutics. "The drugs we are developing at Candid have the potential to go above and beyond the clinical and commercial success of Humira and Rituxan and I am thrilled to be leading the Candid team knowing we can possibly make history by changing the paradigm in how autoimmune diseases are treated."