Welcome to this week’s edition of The Targeted Pulse, a wrap-up of the most significant developments in oncology.This week has seen a mix of groundbreaking approvals, promising trial results, and regulatory hurdles, all of which continue to shape the landscape of targeted cancer therapies. From accelerated approvals for aggressive brain tumors to new hope in breast cancer and colorectal cancer, the pace of innovation remains high, even as some treatments face setbacks. Here is a closer look at the top 5 stories from this week.
Accelerated FDA Approval for Dordaviprone in Diffuse Midline Glioma
In a significant advance, the FDA has granted accelerated approval to dordaviprone, the first targeted therapy for aggressive diffuse midline glioma (DMG). DMG is a rare and devastating brain tumor with a dismal prognosis, and until now, treatment options have been extremely limited.
Dordaviprone, a histone deacetylase (HDAC) inhibitor, specifically targets the epigenetic drivers of DMG. The accelerated approval was based on compelling data from a phase 2 trial, which demonstrated a meaningful improvement in overall response rates and duration of response. This approval represents a new standard of care and provides a glimmer of hope for patients and their families.
While the approval is contingent on further confirmatory trials, the availability of a targeted agent for this historically intractable disease is a landmark moment in neuro-oncology and highlights the power of precision medicine to address even the most challenging cancers
FDA Fast Track Designation for CLD-201 in Sarcoma
Another encouraging story from this week is the FDA’s decision to grant fast track designation to CLD-201, an innovative therapy targeting soft tissue sarcoma. This designation is a critical milestone, as it is designed to accelerate the development and review of treatments that address serious conditions and fill an unmet medical need. CLD-201, developed by Calidi Biotherapeutics, is not a traditional small molecule or antibody. It’s an advanced virotherapy that uses adipose-derived mesenchymal stem cells to carry an oncolytic vaccinia virus directly to tumor sites. This unique delivery mechanism is designed to protect the virus from the immune system, allowing it to multiply within the stem cells and amplify its antitumor effects.
Preclinical data has been promising, showing that this approach can not only destroy cancer cells directly but also activate the patient’s own immune system to fight the tumor. The upcoming phase 1 trial for CLD-201 will be an open-label, multicenter study evaluating its safety, tolerability, and preliminary efficacy across several solid tumor types, including sarcoma. The fast track status signifies the FDA’s recognition of the potential of this novel approach, which is particularly vital for a rare and challenging cancer like soft tissue sarcoma, where new therapeutic options are desperately needed.
FDA Denies Approval of Odronextamab for a Second Time
The regulatory journey for odronextamab has faced another setback. The FDA has once again denied approval for this bispecific antibody in the treatment of follicular lymphoma. The complete response letter (CRL) from the FDA reportedly did not cite concerns about the drug’s efficacy or safety but rather centered on a site inspection.This marks the second time the application has been rejected, following a previous CRL related to enrollment status in confirmatory trials.
Odronextamab is a bispecific antibody that targets both CD20 on B-cell lymphoma cells and CD3 on T cells, activating the immune system to kill malignant cells. While this news is disappointing for patients and clinicians, it is important to note that the drug has already been approved in the European Union for relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. The continued regulatory process underscores the stringent requirements for drug approval in the US and the need for sponsors to meet all administrative and clinical trial benchmarks, even for promising therapies.
Impressive PFS Data for Gedatolisib in Breast Cancer
New clinical trial results for gedatolisib have provided a reason for optimism in the management of advanced hormone receptor-positive/HER2-negative (HR+/HER2–) breast cancer. The trial, which evaluated gedatolisib in combination with fulvestrant and palbociclib, showed that the triplet regimen significantly improved progression-free survival (PFS) compared to the standard of care.
Gedatolisib is a dual PI3K/mTOR inhibitor, and its mechanism of action is designed to overcome resistance to existing endocrine and CDK4/6 inhibitor therapies. This impressive PFS data suggests a potential new therapeutic option for patients who have progressed on or are intolerant to standard treatments. The clinical community is now awaiting the full data presentation, which will provide more detailed insights into the safety profile and durability of response. This trial reinforces the strategy of combining targeted agents to block multiple signaling pathways and highlights the continued progress in extending the lives of patients with advanced breast cancer.
FDA Greenlights Novel Triplet Therapy Trial for Colorectal Cancer
Anbogen Therapeutics has received a significant green light from the FDA to initiate a pivotal phase 1/2 clinical trial for its novel triplet therapy, ABT-301. The trial will focus on patients with metastatic colorectal cancer (mCRC), a disease where new treatment strategies are urgently needed. The investigational regimen combines ABT-301, an oral HDAC inhibitor, with the PD-1 monoclonal antibody tislelizumab and the antiangiogenic agent bevacizumab.
The rationale behind this combination is to target multiple aspects of tumor biology. Preclinical studies have shown that ABT-301 can modulate the tumor microenvironment, transforming “cold tumors” that are typically unresponsive to immunotherapy into “hot tumors” that are more susceptible to immune attack. The inclusion of tislelizumab and bevacizumab further enhances this effect by inhibiting immune checkpoints and blocking blood vessel formation, respectively. This trial represents a promising new approach to overcoming resistance to existing immunotherapies and addressing the unmet clinical needs of patients with mCRC. The community will be watching these developments closely as the trial gets underway.