Repotrectinib

Nuvation Bio Secures $250M Financing Package to Launch Novel Lung Cancer Drug Taletrectinib

3 months ago

• Nuvation Bio has secured a $250 million non-dilutive financing deal with Sagard Healthcare Partners, including $150 million in royalty financing and up to $100 million in term loans. • The financing package is contingent on FDA approval of taletrectinib, a targeted therapy for ROS1-positive non-small cell lung cancer, expected in mid-2025. • The funding will fully support taletrectinib's U.S. commercial launch and ongoing clinical pipeline development without requiring additional capital raises.

Datopotamab Deruxtecan's Role in HR+/HER2- Breast Cancer Treatment: Sequencing and Safety Considerations

4 months ago

• Datopotamab deruxtecan (Dato-DXd) is poised to become a standard treatment for metastatic hormone receptor-positive, HER2-negative breast cancer after prior systemic therapy. • Optimal sequencing of antibody-drug conjugates (ADCs) like Dato-DXd, sacituzumab govitecan, and trastuzumab deruxtecan remains uncertain, especially considering overlapping toxicities. • Real-world toxicity profiles suggest sacituzumab govitecan may cause more cytopenias and diarrhea, while Dato-DXd and trastuzumab deruxtecan are linked to interstitial lung disease. • The lack of overall survival difference in the TROPION-Breast01 trial raises questions about efficacy issues or the impact of crossover between treatment arms.

Experts Address Key Challenges in Implementation of Tumor-Agnostic Therapies and Genetic Testing

4 months ago

• The increasing adoption of tumor-agnostic therapies has highlighted the need for universal genetic testing in oncology practices, with eight drugs now holding FDA pan-tumor approvals as of January 2025. • Healthcare providers face complex decisions regarding genetic testing methodologies, including choices between tissue and liquid biopsies, timing of collection, and interpretation of results. • Clinical implementation challenges include establishing efficient testing workflows, securing genetic counseling resources, and determining appropriate treatment sequencing in cases with limited tumor-specific data.

Arvinas Advances Vepdegestrant into Phase 3 Trials for Breast Cancer and Updates Pipeline Milestones

4 months ago

• Arvinas plans to initiate two Phase 3 trials in 2025 for vepdegestrant in ER+/HER2- metastatic breast cancer, one in the first-line setting with atirmociclib and another in the second-line setting with a CDK4/6 inhibitor. • Topline data from the Phase 3 VERITAC-2 monotherapy trial of vepdegestrant in second-line-plus ER+/HER2- metastatic breast cancer is anticipated in the first quarter of 2025. • Arvinas is set to present initial data from the Phase 1 trial of ARV-393 in B-cell lymphomas and file an IND application for a novel PROTAC KRAS G12D degrader in 2025. • Phase 1 trial with PROTAC LRRK2 degrader ARV-102 in patients with Parkinson’s disease has been initiated, with data expected to be presented in the first half of 2025.

FDA Approvals in 2024: Advancing Treatment Paradigms in Solid Tumors and Hematologic Malignancies

5 months ago

• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies. • Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine. • Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes. • Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.

Opdivo Plus Yervoy Demonstrates Improved Outcomes in MSI-H/dMMR Metastatic Colorectal Cancer

5 months ago

• The combination of Opdivo and Yervoy significantly reduced the risk of disease progression or death by 38% compared to Opdivo alone in MSI-H/dMMR mCRC patients. • The CheckMate-8HW trial showed improved progression-free survival rates at 12, 24, and 36 months with the Opdivo/Yervoy combination versus Opdivo monotherapy. • The objective response rate was higher with Opdivo plus Yervoy (71%) compared to Opdivo alone (58%), indicating a greater proportion of patients experienced tumor shrinkage. • The safety profile of the Opdivo/Yervoy combination was consistent with previous findings, supporting its potential as a new standard of care.

Innovent's Taletrectinib (DOVBLERON®) Receives Expanded Approval in China for ROS1-Positive NSCLC

5 months ago

• China's NMPA has approved Innovent's taletrectinib for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). • The approval was based on positive outcomes from the Phase II TRUST-I trial, which showed high and durable overall responses. • In TKI-naïve patients, taletrectinib achieved a confirmed objective response rate of 91% and intracranial cORR of 88%. • Taletrectinib is now approved for both first-line and previously treated ROS1-positive NSCLC patients in China.

Pancreatic Cancer: Advances in Treatment and Research Bring Hope in 2024

5 months ago

• The five-year relative survival rate for pancreatic cancer has risen to 13%, marking the third consecutive year of improvement, yet it remains the lowest among major solid tumors. • Four new drug approvals for pancreatic cancer occurred in 2024, including one first-line treatment and three targeted agents for previously treated advanced disease. • A Phase 3 clinical trial demonstrated an overall survival benefit using Tumor Treating Fields (TTFields) in combination with chemotherapy for unresectable, locally advanced pancreatic cancer. • Precision medicine is advancing with the FDA approval of Bizengri for NRG1 fusion-positive pancreatic cancer and the ongoing RASolute 302 trial evaluating RMC-6236, a RAS inhibitor.

MSK Researchers Spearhead Advances in Cancer Treatment, Leading to 11 FDA Approvals in 2024

5 months ago

• Memorial Sloan Kettering Cancer Center (MSK) made significant strides in cancer treatment in 2024, including novel vaccines, drugs enhancing radiation, and advanced diagnostics. • A vaccine targeting KRAS mutations in pancreatic and colorectal cancers showed promising early results in stimulating the immune system. • Imlunestrant, combined with abemaciclib, demonstrated a significant reduction in cancer progression or death in ER+, HER2- advanced breast cancer patients resistant to standard therapy. • MSK played a pivotal role in clinical trials leading to 11 FDA approvals in 2024, spanning new uses for existing drugs, effective drug combinations, and novel targeted therapies.

Osler Research Institute Advances Cancer Care with Novel Clinical Trials and Diagnostics

5 months ago

• Osler Research Institute is conducting over 70 clinical trials, including studies on new anti-tumor medications, to improve treatments and address community health needs. • A breakthrough in liquid biopsy research at Osler has reduced tumor diagnosis times from weeks to days, enabling faster, tailored healthcare decisions. • The TRIDENT-1 trial is evaluating repotrectinib as a potential treatment for advanced or metastatic solid tumors with specific DNA alterations. • Osler is collaborating with Toronto Metropolitan University's School of Medicine, supporting the education of future healthcare professionals in Brampton.

Taletrectinib Approved in China for ROS1-Positive NSCLC, Showing Promise in TKI-Pretreated and Naive Patients

6 months ago

• China's NMPA has approved taletrectinib for treating adults with locally advanced or metastatic ROS1-positive NSCLC previously treated with ROS1 TKIs. • The approval was based on the phase 2 TRUST-I trial, which demonstrated a 51.5% ORR in patients pretreated with crizotinib, with a median DOR of 10.6 months. • Taletrectinib has also received priority review for first-line treatment of ROS1-positive NSCLC, supported by data showing a 90.6% ORR in TKI-naive patients. • Clinical trials show taletrectinib's efficacy in CNS penetration and activity against resistance mutations, offering a potential best-in-class safety profile.

Nuvalent's Zidesamtinib Shows Promise in ROS1-Positive NSCLC, Anticipates FDA Submission

6 months ago

• Nuvalent plans to release pivotal data from the Phase 1/2 ARROS-1 study of zidesamtinib in H1 2025 for advanced ROS1-positive NSCLC. • The company aims to submit a New Drug Application (NDA) for zidesamtinib in mid-2025, potentially securing its first FDA approval by 2026. • Early ARROS-1 data showed a 44% overall response rate in previously treated patients, with notable intracranial activity. • Nuvalent is in discussions with the FDA for a potential line-agnostic approval of zidesamtinib, supported by data from TKI-naïve patients.

Avistone's ANS03, a Novel ROS1/NTRK Inhibitor, Receives FDA IND Clearance

6 months ago

• Avistone Biotechnology's ANS03, a next-generation tyrosine kinase inhibitor targeting ROS1 and NTRK, has received FDA IND clearance. • ANS03 is designed to overcome resistance mutations in ROS1/NTRK fusion-positive cancers, addressing a critical unmet need. • Clinical trials for ANS03 are expected to begin in Q1 2025, focusing on patients with advanced or metastatic tumors harboring ROS1 or NTRK alterations.

Oncolytics Biotech and Bio-Path Holdings Announce Promising Cancer Therapy Advancements

6 months ago

• Oncolytics Biotech presented data at the ASCO GI Symposium, highlighting pelareorep's potential in treating relapsed anal and metastatic pancreatic cancers. • A GOBLET study cohort showed a 33% objective response rate in relapsed anal cancer patients treated with pelareorep and atezolizumab, including a complete response lasting over 15 months. • Bio-Path Holdings reported a meaningful patient response in a Phase 1/1b trial of BP1002 for refractory/relapsed AML, with stable disease and reduced blast count after one treatment cycle. • Bio-Path Holdings' BP1001-A demonstrated continued tumor reduction and stable disease in a solid tumor patient, alongside durable remissions in AML patients treated with prexigebersen.

Molecular Testing Drives Personalized Treatment Approaches in Endometrial Cancer

6 months ago

• Molecular classification of endometrial cancer, including POLE, mismatch repair, and TP53 mutations, is becoming standard of care and guiding more targeted treatment decisions for patients. • Immunotherapy shows significant benefit when combined with chemotherapy, particularly in mismatch repair deficient tumors, with FDA approvals for dostarlimab, pembrolizumab, and durvalumab in this space. • HER2-targeted therapy with fam-trastuzumab deruxtecan shows promising responses in HER2-positive endometrial cancers, which comprise 20-30% of cases, even in heavily pretreated patients.

Zai Lab's Augtyro Included in China's National Reimbursement Drug List for ROS1+ NSCLC

6 months ago

• Zai Lab's Augtyro (repotrectinib) has been added to China's National Reimbursement Drug List (NRDL) for treating adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). • The NRDL update also includes the renewal of Nuzyra (omadacycline) for community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). • Qinlock (ripretinib) is also renewed for advanced gastrointestinal stromal tumor (GIST) patients who have received prior treatment with three or more kinase inhibitors. • The inclusion of these drugs in the NRDL aims to improve patient access to innovative treatments at more affordable costs throughout China.

Tislelizumab Gains Category 1 Recommendation in NCCN Guidelines for Hepatocellular Carcinoma

6 months ago

• Tislelizumab-jsgr (Tevimbra) has been added to the NCCN guidelines as a category 1 recommended regimen for first-line systemic therapy in HCC. • The NCCN guidelines are updated regularly, and healthcare professionals should ensure they are using the latest version to inform their practice. • Identifying biomarkers to predict response to checkpoint inhibitors remains a key challenge in HCC treatment, as many patients do not benefit from current therapies.

FDA Approvals of Ribociclib and Inavolisib Reshape HR+ Breast Cancer Treatment

6 months ago

• Ribociclib's approval for adjuvant use in high-risk HR+/HER2- early breast cancer marks a significant advancement, potentially benefiting a broader patient population. • Inavolisib, combined with palbociclib and fulvestrant, gains FDA approval for endocrine-resistant, PIK3CA-mutated HR+/HER2- advanced breast cancer, improving progression-free survival. • The FDA emphasizes the need for increased diversity in clinical trials and post-marketing studies to ensure the safety and efficacy of new drugs across all patient populations. • Dose optimization strategies, like those promoted by Project Optimus, are crucial for balancing efficacy and toxicity in novel targeted therapies for breast cancer.

Repotrectinib Recommended for EU Approval in ROS1+ NSCLC and NTRK+ Solid Tumors

6 months ago

• The EMA's CHMP recommended repotrectinib for adult patients with advanced ROS1-positive NSCLC, addressing the unmet need for new therapies in this population. • Repotrectinib is also recommended for NTRK fusion-positive solid tumors in adult and pediatric patients (12+), particularly after prior NTRK inhibitor treatment. • The recommendation is based on TRIDENT-1 and CARE trials, demonstrating durable activity and robust responses in both ROS1-positive NSCLC and NTRK-positive solid tumors. • Repotrectinib previously received FDA approval for ROS1-positive NSCLC (November 2023) and NTRK-positive solid tumors (accelerated approval, June 2024).

CHMP Recommends Opdivo Plus Yervoy for First-Line MSI-H/dMMR Metastatic Colorectal Cancer

6 months ago

• The European Medicines Agency's CHMP has recommended approval of Opdivo plus Yervoy for first-line treatment of MSI-H or dMMR unresectable or metastatic colorectal cancer. • The positive opinion is based on the CheckMate -8HW trial, which demonstrated a statistically significant improvement in progression-free survival compared to chemotherapy. • The combination showed a 79% reduction in the risk of disease progression or death, with a manageable safety profile consistent with previous data. • This dual checkpoint inhibitor treatment offers a transformative benefit for MSI-H/dMMR metastatic colorectal cancer patients, addressing an area of unmet need.

Drug Development Updates