In September and October, the U.S. Food and Drug Administration (FDA) released statements regarding the Agency’s approval of a number of oncology drug products across several solid tumors and hematologic malignancies. A summary of these approvals is provided here.
Combination Approved in dMMR Colon Cancer
On October 8, the FDA approved atezolizumab (Tecentriq), a humanized, engineered monoclonal antibody of IgG1 isotope against PD-L1, in combination with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients aged 2 years and older with stage III mismatch repair–deficient (dMMR) colon cancer.
At the same time, the Agency also approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) in combination with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients aged 12 years and older who weigh 40 kg or more with stage III dMMR colon cancer. Approvals were based on the Phase III ATOMIC study (ClinicalTrials.gov identifier NCT02912559).
ATOMIC
Efficacy of the atezolizumab combination regimens was evaluated in ATOMIC, a multicenter, randomized, open-label, active-controlled trial in 711 adults and 1 pediatric patient with stage III dMMR colon cancer after a complete resection of the primary tumor with no evidence of residual lymph node involvement or metastatic disease. Patients were randomly assigned 1:1 to receive either atezolizumab in combination with mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) for 12 cycles followed by atezolizumab monotherapy for 6 months, or mFOLFOX6 alone for 12 cycles.
The major efficacy outcome measure was disease-free survival as assessed by the investigator. The hazard ratio for the disease-free survival comparison was 0.50 (95% confidence interval = 0.35–0.73, P = .0001), and the median disease-free survival was not reached in either arm.
The recommended atezolizumab dose for adult patients is 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks administered intravenously in combination with chemotherapy for 6 months, followed by atezolizumab as a single agent for 6 months or until disease recurrence or unacceptable toxicity.
For pediatric patients, the recommended dose of atezolizumab is 10 mg/kg (up to a maximum of 840 mg) every 2 weeks or 15 mg/kg (up to a maximum of 1,200 mg) every 3 weeks in combination with chemotherapy for 6 months, followed by atezolizumab as a single agent for 6 months or until disease recurrence or unacceptable toxicity, whichever occurs first.
The recommended dosage of atezolizumab and hyaluronidase-tqjs in adults and pediatric patients 12 years of age and older who weigh 40 kg or more is one 15 mL injection every 3 weeks (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously in combination with chemotherapy for 6 months, followed by atezolizumab and hyaluronidase-tqjs as monotherapy for 6 months or until disease recurrence or unacceptable toxicity, whichever occurs first.
Dosage has not been established for pediatric patients under 12 years and older who weigh less than 40 kg (88 pounds).
The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Triplet Combination for HER2-Positive Breast Cancer Maintenance Therapy
On October 7, the FDA approved tucatinib (Tukysa), a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab and pertuzumab for the maintenance treatment of adult patients with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment. Approval was based on data from the HER2CLIMB trial 05 (ClinicalTrials.gov identifier NCT05132582).
Efficacy of tucatinib was evaluated in 654 adult patients in HER2CLIMB- a randomized, double-blind, placebo-controlled trial. Eligible patients were required to have HER2-positive, unresectable locally advanced or metastatic breast cancer, with or without brain metastases, and no evidence of disease progression by investigator assessment after induction treatment with four to eight cycles of trastuzumab, pertuzumab, and a taxane.
Patients received tucatinib at 300 mg or placebo orally twice-daily with trastuzumab and pertuzumab intravenously, or with a fixed-dose combination of trastuzumab, pertuzumab, and hyaluronidase administered subcutaneously. Patients with hormone receptor–positive disease were permitted to continue endocrine therapy. Patients were treated until disease progression or unacceptable toxicity.
The primary efficacy outcome measure was progression-free survival by investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1; overall survival was an additional efficacy outcome measure. Median progression-free survival was 24.9 months (95% confidence interval [CI] = 21.3 months to not reached) in the tucatinib arm and 16.3 months (95% CI = 12.6–18.7 months) in the placebo arm (hazard ratio = 0.64, P < .0001). At the time of the progression-free survival analysis, overall survival data were not mature.
The recommended tucatinib dosage is 300 mg orally twice daily in combination with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. Refer to the prescribing information of the combination agents for dosing and administration information.
The prescribing information includes a boxed warning for hepatotoxicity, as well as warnings and precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.
First-Line Therapy for CLL/SLL
Pirtobrutinib (Jaypirca) received FDA approval on October 2 for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion. Approval was based on the BRUIN CLL-313 trial (ClinicalTrials.gov identifier NCT05023980).
Efficacy of pirtobrutinib was evaluated in the randomized, open-label, active-controlled BRUIN CLL-313 trial in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p. In the study, patients were randomly assigned 1:1 to receive pirtobrutinib (n = 141) until disease progression or bendamustine plus a rituximab product (n = 141) for six cycles.
The main efficacy outcome measure was progression-free survival as assessed by an independent review committee. With an estimated median follow-up of 28 months, the median progression-free survival was not estimable in the pirtobrutinib arm and 33.5 months (95% confidence interval [CI] = 32.7 to not estimable) in the bendamustine/rituximab arm (hazard ratio [HR] = 0.20; 95% CI = 0.11–0.37; P < .0001).
Dosage and Safety
The recommended pirtobrutinib dose is 200 mg orally once-daily until disease progression or unacceptable toxicity.
At the time of the primary analysis of progression-free survival, overall survival data were still immature. The median overall surival was not reached in either arm with a total of 13 deaths: 3 deaths (2.1%) in the pirtobrutinib arm and 10 deaths (7.1%) in the control arm.
The most common (≥ 20%) adverse reactions occurring in patients receiving pirtobrutinib were upper respiratory tract infections (27%), rash (22%), and COVID-19 (21%). The most common (> 10%) grade 3 or 4 laboratory abnormality was neutrophil count decrease. Serious adverse reactions occurred in 28% of patients taking pirtobrutinib.
The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.
Combination Regimen for Advanced Clear Cell RCC
On September 24, the FDA approved the HIF-2α inhibitor belzutifan (Welireg) in combination with the tyrosine kinase inhibitor lenvatinib (Lenvima) for adults with advanced renal cell carcinoma with a clear cell component following treatment with a PD-1 or PD-L1 inhibitor. Efficacy was evaluated in LITESPARK-011 (ClinicalTrials.gov identifier NCT04586231).
LITESPARK-011 was an open-label, randomized, active-controlled trial in 747 patients with advanced clear cell RCC. Eligible patients had locally advanced or metastatic clear cell RCC which progressed on or after receipt of a PD-1 or PD-L1 inhibitor, or within 6 months of completing adjuvant therapy with a PD-1 inhibitor. Patients were randomly assigned 1:1 to receive either belzutifan in combination with lenvatinib or cabozantinib alone.
The major efficacy outcome measures were progression-free survival measured by blinded independent central review using Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival; objective response rate was an additional efficacy outcome measure.
There was a statistically significant improvement in progression-free survival for the belzutifan and lenvatinib arm compared to the cabozantinib arm. Median progression-free survival was 14.6 months (95% confidence interval [CI] = 11.1–16.6 months) in the belzutifan and lenvatinib arm and 10.6 months (95% CI = 9.2–11.1 months) in the cabozantinib arm (hazard ratio [HR] = 0.74, 95% CI = 0.61–0.89, one-sided P = .00095).
The final analysis of overall survival was not statistically significant. Median overall survival was 33.7 months (95% CI = 29.0–46.9 months) and 28.6 months (95% CI = 24.1–31.4 months) in the respective arms (HR = 0.85, 95% CI = 0.70–1.03). Objective response rate was 53% (95% CI = 47%–58%) and 40% (95% CI = 35%–45%) in the respective arms (one-sided P = .0002).
The recommended dosage is 20 mg of lenvatinib in combination with 120 mg of belzutifan once daily until disease progression or unacceptable toxicity.
The belzutifan prescribing information includes a boxed warning for embryo-fetal toxicity, as well as warnings and precautions for anemia and hypoxia. For the belzutifan and lenvatinib combination, warnings and precautions also include cardiac dysfunction.
The lenvatinib prescribing information includes warnings and precautions for hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, impaired wound healing, osteonecrosis of the jaw, and embryo-fetal toxicity.
TKI-Naive Advanced ROS1-Positive NSCLC
The FDA approved updated labeling of taletrectinib (Ibtrozi), an oral, CNS-active, selective next-generation ROS1 inhibitor therapy for non-small cell lung cancer (NSCLC), reflecting a median duration of response of 49.7 months in TKI-naive patients in the TRUST-I trial, and validating more than 4 years of sustained clinical benefit.
Full FDA approval for taletrectinib was granted in June 2025 for the treatment of locally advanced or metastatic ROS1+ NSCLC across lines of therapy.
The sNDA approval reflects a median follow-up of 51 months for patients from the TRUST-I study and incorporates an additional 14 months of data from both of the pivotal TRUST-I and TRUST-II (Clinical Trials ID NCT04919811) studies as of an August 2025 data cutoff, according to a news statement from Nuvation Bio, which announced the recent approval.
Acccording to the statement, many patients remained on therapy for extended periods with a continued response highlighting the long-term durability and tolerability of taletrectinib and reinforcing its importance as a treatment option for advanced ROS1+ NSCLC.
These data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 and simultaneously published in the Journal of Clinical Oncology.
To learn more, see a video interview with investigator Lyudmila A. Bazhenova, MD, of the University of California, San Diego, who presented the updated data from the phase II TRUST-I and TRUST-II trials at the 2026 AACR Annual Meeting. Visit The ASCO Post/videos.
For more information visit www.FDA.gov/drugs.
