The Targeted Pulse: Palazestrant/Ribociclib Shows Favorable Efficacy, Approvals in SCLC, and More


Interim results show promising efficacy of palazestrant/ribociclib in ER+/HER2– metastatic breast cancer, an approval for tarlatamab-dlle, and data suggesting early ctDNA kinetics as a potential pharmacodynamic biomarker. We also cover the initiation of dosing quaratusugene ozeplasmid/atezolizumab in SCLC and more.

Sketch of breast cancer tissue

Favorable Interim Results of Palazestrant With Ribociclib in ER+/HER2– mBC

The combination of palazestrant (OP-1250) and ribociclib (Kisqali) demonstrated promising efficacy for the management of estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer according to interim results. These data are from the ongoing phase 1b/2 trial (NCT05508906) that was presented at the 2024 European Society for Medical Oncology Breast Cancer Annual Congress in Berlin, Germany.

“…Palazestrant possesses key characteristics that make it a potential backbone endocrine therapy of preference for ER+/HER2[-negative] breast cancer, both as a monotherapy and in combination with other targeted agents,” Sean P. Bohen, MD, PhD, said in a press release. “We are grateful to the approximately 300 women to date who have participated across our clinical trials and are excited with the progress we are making.” Bohen is president and chief executive officer of Olema Oncology.

Sketch of DNA strand

A Potential Biomarker Found in Early ctDNA Kinetics Across Tumor Types

Preliminary circulating tumor DNA (ctDNA) kinetics could be used as apharmacodynamic biomarker according to a recent analysis. The biomarker would be especially useful with targeted therapies and the analysis offers early biologic proof of concept. The phase 1 prospective, single-center, analysis included the following advanced cancer types: lung, colorectal, cervical, adrenocortical carcinoma, cholangiocarcinoma, endometrial, head and neck squamous cell carcinoma, mesothelioma, esophageal, and pancreatic.

“In 100% [of] patients with partial response prior to imaging…. [Among] 8 patients with stable disease/progressive disease but early ctDNA response, 4 had serial time points for ctDNA kinetics [and] in all 4 patients ctDNA burden subsequently increased, [which was] consistent with imaging,” Aaron Tan, MBBS, PhD, FRACP, said in a presentation of the data. Tan is a medical oncologist at the National Cancer Centre, Singapore.

Sketch of human lungs

Tarlatamab Scores an FDA Win in Small Cell Lung Cancer

Tarlatamab-dlle (Imdelltra) has been granted FDA approval for the treatment of small cell lung cancer (SCLC) that has progressed on or after platinum-based chemotherapy. The approval is based on data from the phase 2 DeLLphi-301 study (NCT05060016), which was presented at the 2023 European Society of Medical Oncology Congress. Tarlatamab-dlle is the first bispecific T-cell engager approved for a major solid tumor and the first therapeutic option for the treatment of extensive-stage SCLC.

“Tarlatamab represents a new immunotherapeutic approach for SCLC, a tumor type that is characterized by an immunosuppressive microenvironment,” the researchers wrote a simultaneous publication of the findings in the New England Journal of Medicine.

Treatment Optimization Discussion of Sacituzumab for HR+, HER2- Breast Cancer

In a case-based discussion moderated by Stephenie L. Graff, MD, clinicians specializing in the management of hormone receptor–positive, HER2-negative metastatic breast cancer give varying perspectives on the optimal treatment approach in first, second, and third-line settings. Sequencing of antibody-drug conjugates in the first line setting was explored as well as the use of sacituzumab govitecan in lieu of trastuzumab deruxtecan (Enhertu; T-DXd) for HER2-low disease, among others.

“[if the patient had] HER2-low disease, I would choose T-DXd before sacituzumab. In terms of the HER2-negative after the second biopsy, the algorithm would be either capecitabine prior to going on to sacituzumab. In the event the patient has not seen any prior chemotherapy or taxanes in the adjuvant setting and if they don’t have any issues, then I have sometimes used eribulin [Halaven] ahead, depending on the volume of disease,” Ankur Mehta, MD, oncologist in Boston, Massachusetts with 24 years of experience, said.

The First Patient to Receive Quaratusugene Ozeplasmid/Atezolizumab in ES-SCLC

The phase 1, dose-escalation for the Acclaim-3 trial (NCT05703971), evaluating patients with extensive-stage small cell lung cancer (SCLC), has commenced. Patients who received 3 to 4 cycles of carboplatin, etoposide, and atezolizumab and achieve complete response, partial response, or stable disease are now receiving quaratusugene ozeplasmid (Reqorsa) and atezolizumab (Tecentriq) as maintenance therapy every 21 days until disease progression.

“Patients receiving [atezolizumab] as maintenance therapy have a median progression-free survival of 2.6 months after the start of maintenance therapy. With such limited benefit from current treatments, we believe the combination of [quaratusugene ozeplasmid] and [atezolizumab] can provide a promising new therapeutic option for the treatment of SCLC,” said Ryan Confer, president and chief executive officer at Genprex, in a press release.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.

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