The Targeted Pulse: Two Breakthrough Therapy Designations in Breast Cancer and NSCLC, FDA Approvals, and More

Inavolisib Regimen Earns Breakthrough Therapy Designation for PIK3CA+ Breast Cancer

The regimen inavolisib (GDC-0077) plus palbociclib (Ibrance) and fulvestrant (Faslodex) was given a breakthrough therapy designation for hormone receptor-positive, HER2-negative, PIK3CA-mutated breast cancer. The data supporting this designation are from the phase 3 INAVO120 trial (NCT04191499), which demonstrated that the regimen more than doubled progression-free survival in the first-line setting. Other phase 3 trials, INAVO121 (NCT05646862) and INAVO122 (NCT05894239), are exploring inavolisib’s efficacy in treating PIK3CA-mutated locally advanced or metastatic breast cancer.

“This promising inavolisib-based regimen could transform the PI3K inhibitor class, potentially becoming the standard of care for this patient population in the first-line setting,” Levi Garraway, MD, PhD, said in a press release. Garraway is chief medical officer and head of global product development at Roche.

Infigratinib Loses FDA Approval for Cholangiocarcinoma Treatment

The FDA has withdrawn its approval for infigratinib (Truseltiq) in the treatment of cholangiocarcinoma. The discontinued phase 3 PROOF trial (NCT03773302) was designed to assess the safety and efficacy of infigratinib compared with standard-of-care gemcitabine plus cisplatin for the frontline treatment of patients with unresectable, recurrent, or metastatic cholangiocarcinoma harboring FGFR2 gene fusions and translocations.

Following the accelerated approval of infigratinib in May 2021, QED Therapeutics, the sponsor, faced difficulties in enrolling participants for the necessary confirmatory study. Because of this, along with the determination that continued distribution of infigratinib for second-line cholangiocarcinoma treatment was not commercially viable, and the sponsor opted to voluntarily withdraw the drug.

Guiding Treatment Decisions with Targeted Therapies for EGFR-Mutated NSCLC

Advancements in targeted therapy are reshaping treatment approaches for non-small cell lung cancer (NSCLC) and understanding tumor resistance and mutations is essential. Because patients with EGFR-mutated NSCLC benefit from tailored therapies, the National Comprehensive Cancer Network (NCCN) guidelines emphasize mutation testing to guide treatment decisions. For example, osimertinib (Tagrisso) is preferred for EGFR-positive NSCLC, with emerging options such as amivantamab-vmjw (Rybrevant) for those who progress after osimertinib.

“The combination of tissue and plasma testing [is] acceptable [by the NCCN guidelines], in any combination: tissue first, liquid first, or the combination of the 2,” explained Martin Dietrich, MD, PhD. “Which test you use depends on the individual case; sometimes you have a beautiful big core biopsy from the liver and that’ll probably be OK in an asymptomatic patient, but the ideal plan is a fast and comprehensive tissue testing approach in the beginning.” Dietrich is a medical oncologist at The US Oncology Network and assistant professor of internal medicine at the University of Central Florida College of Medicine in Orlando.

Breakthrough Therapy Designation Awarded to NVL-655 in ALK-Positive NSCLC

NVL-655 received a breakthrough therapy designation from the FDA for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have received 2 or more ALK tyrosine kinase inhibitors. The phase 1/2 ALKOVE-1 study (NCT05384626) is currently evaluating the agent in a dose-escalation and -expansion study design.

“Our team is committed to expeditiously advancing NVL-655 in recognition of the continued need for innovation for patients with ALK-positive NSCLC who have exhausted available therapies. We expect to provide an update from the ALKOVE-1 trial of NVL-655 at a medical meeting in the second half of this year,” said Darlene Noci, chief development officer at Nuvalent, in a press release.

TN0155 With Spartalizumab or Ribociclib Show Positive Responses in Solid Tumors

In the phase 1b dose escalation, open-label study (NCT04000529), TNO155 with either spartalizumab (PDR001) or ribociclib (Kisqali) showed acceptable safety and tolerability across solid tumors. In the TNO155 and spartalizumab cohort, included patients were diagnosed with advanced head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, colorectal cancer, or EGFR/ALK wild-type NSCLC. Patients eligible for the TNO155/ribociclib combination had any type of advanced solid tumor.

“The safety profiles of the combinations were consistent with those observed with each single agent, and no new safety signals were identified,” said lead study author Omar Saavedra Santa Gadea, MD, of the Early Clinical Drug Development Group (phase 1 unit) at Vall d’Hebron Institute of Oncology in Barcelona, Spain, in a presentation of the data.

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