The FDA approved talazoparib (Talzenna) plus enzalutamide on Oct 26, 2026 for adults with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer with HRR gene mutations, as detected by an FDA-authorized test. Approval was supported by the phase 3 TALAPRO-3 trial showing a statistically significant radiographic progression-free survival benefit versus placebo plus enzalutamide (HR 0.48; p<0.0001). Overall survival data were immature at the time of rPFS analysis.
On Oct 26, 2026, the FDA approved talazoparib (Talzenna; Pfizer) in combination with enzalutamide for adults with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer with homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test.
The FDA previously approved FoundationOne CDx and FoundationOne Liquid CDx as companion diagnostic devices to identify patients with prostate cancer with HRR gene alterations for treatment with talazoparib plus enzalutamide.
Supporting evidence
Efficacy and safety were evaluated in TALAPRO-3 (NCT04821622), a randomized, double-blind, placebo-controlled trial in which 599 patients with HRR gene–mutated mAPMN/S prostate cancer were randomized 1:1 to enzalutamide + talazoparib or enzalutamide + placebo; all patients received continuous androgen deprivation therapy. HRR mutation status (including ATM, ATR, BRCA1/2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) was prospectively determined using tumor tissue or ctDNA NGS tests.
The primary endpoint was investigator-assessed rPFS (RECIST 1.1 and PCWG3). Median rPFS was not reached with talazoparib/enzalutamide vs 45.8 months with placebo/enzalutamide (HR 0.48, 95% CI 0.36–0.65; p<0.0001). OS data were immature.
Key labeling elements
Warnings/precautions include MDS/AML, myelosuppression, and embryo-fetal toxicity. Recommended talazoparib dose: 0.5 mg orally once daily with enzalutamide until progression or unacceptable toxicity; patients should also receive a GnRH analog or have had bilateral orchiectomy.
The review was conducted under Project Orbis with collaboration from Australia’s TGA and Health Canada; reviews remain ongoing at partner agencies.
Regulatory approval news: The FDA has granted traditional approval for pembrolizumab (Keytruda) or pembrolizumab plus berahyaluronidase alfa-pmph (Keytruda QLEX) for adult and pediatric patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors (≥13 mut/Mb by an FDA-authorized test) that progressed after prior treatment and have no satisfactory alternatives. The action converts a prior accelerated approval and updates the TMB-H cutoff from ≥10 to ≥13 mut/Mb based on evidence from KEYNOTE-158.
PembrolizumabBerahyaluronidase Alfa and Pembrolizumab
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FDA converts pembrolizumab TMB-H indication to traditional approval and raises cutoff to ≥13 mut/Mb
Type: Regulatory approval (FDA)
The FDA granted traditional approval for pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda QLEX) for adult and pediatric patients with unresectable or metastatic TMB-H solid tumors defined as ≥13 mutations/megabase, as determined by an FDA-authorized test, whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options.
This action converts the previous accelerated approval for TMB-H solid tumors (previously ≥10 mut/Mb) to traditional approval and amends the biomarker definition. The FDA stated that efficacy supporting traditional approval was not confirmed in patients with TMB 10 to <13 mut/Mb.
Evidence base (KEYNOTE-158; NCT02628067)
Efficacy was evaluated in 220 patients with TMB ≥13 mut/Mb (145 in Cohort M; 75 in Cohorts A–J) receiving pembrolizumab, assessed by BICR per RECIST v1.1 (modified). Across groups, ORR was 36% (95% CI, 30–43), and 58% of responders had DOR ≥12 months.
Safety and dosing
Safety was reported as consistent with known pembrolizumab monotherapy safety, with labeled warnings including immune-mediated adverse reactions, infusion-related reactions, allogeneic HSCT complications, and embryo-fetal toxicity. Recommended adult dosing: 200 mg q3w or 400 mg q6w (up to 24 months); pediatric: 2 mg/kg q3w (max 200 mg; up to 24 months).
Regulatory approval: On Oct 19, 2026, the FDA granted accelerated approval to dostarlimab (Jemperli; GSK) for adults with Stage II/III locally advanced rectal cancer that is MSI-H or dMMR, as determined by an FDA-authorized test. Approval was supported primarily by the single-arm AZUR-1 study, which reported a 47% sustained clinical complete response at 12 months (ICR) among 116 evaluable patients, and an ICR ORR of 79%. Safety includes immune-mediated toxicities and infusion reactions.
Dostarlimabrectal disease
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FDA accelerated approval: dostarlimab in MSI-H/dMMR locally advanced rectal cancer (Oct 19, 2026)
The FDA granted accelerated approval (Oct 19, 2026) to dostarlimab (Jemperli; GSK) for adults with Stage II/III locally advanced rectal cancer (LARC) that is microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-authorized test for solid tumors.
Supporting efficacy evidence
Efficacy was evaluated in AZUR-1 (NCT05723562), a multicenter, single-arm, open-label trial in 154 previously untreated patients with histologically confirmed MSI-H/dMMR Stage II/III LARC. Dostarlimab was given 500 mg IV every 3 weeks for nine cycles unless unacceptable toxicity or progression. Response assessment used endoscopy, rectal MRI, and CT.
Among 116 ICR-evaluable patients, cCR12 (sustained clinical complete response for 12 months) was 47% (95% CI 27–56), and ORR per ICR was 79% (95% CI 71–85). Median follow-up was 26.3 months; no progression was reported among patients with cCR12, cCR, or near CR at data cutoff.
FDA also reviewed investigator-led NCT04165772 (n=50): cCR12 93% (95% CI 82–99) and ORR 100% (95% CI 93–100).
Dosing and key safety warnings
Recommended dose: 500 mg every 3 weeks until progression or unacceptable toxicity, up to nine cycles. Label warnings include immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.
Review used Project Orbis and RTOR; international partner reviews were ongoing at the time described.
Regulatory approval: On Oct 14, 2026, the FDA approved an expanded indication for nogapendekin alfa inbakicept-pmln (Anktiva) administered intravesically with BCG for adults with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC). The label now includes patients with high-grade papillary-only tumors, revising the prior indication limited to carcinoma in situ (CIS) with or without papillary tumors. The expansion was based on FDA review and extrapolation from previously demonstrated efficacy in CIS-containing disease.
The FDA approved nogapendekin alfa inbakicept-pmln (Anktiva; Altor BioScience, LLC/ImmunityBio) in combination with Bacillus Calmette-Guérin (BCG) for adults with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC), expanding the prior indication from CIS (± papillary tumors) to also include high-grade papillary-only tumors.
Evidence base and rationale
Efficacy was previously demonstrated in Cohort A of QUILT-3.032 (NCT03022825), a single-arm multicenter trial (n=77) in BCG-unresponsive, high-risk NMIBC with CIS (± Ta/T1). Patients received intravesical induction with BCG followed by maintenance up to 37 months. The primary outcome was complete response (CR) (cystoscopy, urine cytology, biopsy); duration of response (DoR) was additional.
CR rate: 62% (95% CI, 51–73)
Among responders: 58% had DoR ≥12 months; 40% had DoR ≥24 months
For the expanded population, FDA stated the decision was based on review of available scientific information and extrapolation from CIS-containing disease due to overlapping clinical/non-clinical features.
Safety and dosing highlights
Common adverse reactions (≥15%) included increased creatinine, dysuria, hematuria, urinary frequency/urgency, UTI, increased potassium, musculoskeletal pain, chills, and pyrexia. The prescribing information includes a warning that delaying cystectomy can lead to metastatic bladder cancer.
Full prescribing information will be posted on Drugs@FDA.
Research news (Oct 8, 2026) from the US National Cancer Institute highlights decades of federally funded work that helped convert RAS—implicated in roughly one-third of cancers and >90% of pancreatic cancers—from an “undruggable” target to one with multiple inhibitors. The piece cites FDA approval of sotorasib (2021) and accelerated approval of adagrasib (2022) for KRAS G12C–mutant NSCLC, and describes newer, broader-acting RAS inhibitors (e.g., daraxonrasib) and additional investigational agents in clinical trials.
The US National Cancer Institute (NCI) summarized progress against RAS-driven cancers, noting that mutations in RAS family genes help drive roughly a third of all cancers, including >90% of pancreatic cancers. The article describes why RAS was long considered “undruggable,” citing its relatively smooth protein surface, and outlines how decades of basic research elucidated RAS structure and function as a GDP/GTP-regulated molecular switch.
A cited scientific inflection point was a 2013 Nature report describing a previously hidden pocket in mutant KRAS and a molecule shown to be effective against a mutant-KRAS cancer cell line.
NCI also highlighted its RAS Initiative (launched in 2013) as a coordinating hub that has generated structural/biochemical data, assays, and shared reagents, and that co-discovered investigational compounds now in clinical trials: BBO-8520, BBO-11818, and BBO-10203.
The item references regulatory milestones but is not itself an approval announcement. It notes the FDA approved sotorasib (May 2021) for KRAS G12C–mutant NSCLC, and granted accelerated approval to adagrasib (Dec 2022) for locally advanced or metastatic KRAS G12C–mutant NSCLC. It also states that newer inhibitors such as daraxonrasib (targeting multiple RAS mutations) have shown effectiveness against metastatic pancreatic cancer, without providing trial details.
Regulatory approval: On Oct 8, 2026, the FDA approved atezolizumab (Tecentriq) plus a fluoropyrimidine and oxaliplatin for adjuvant treatment of adult and pediatric patients ≥2 years with resected Stage III mismatch repair deficient (dMMR) colon cancer. The FDA also approved subcutaneous atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) plus the same chemotherapy for patients ≥12 years and ≥40 kg. Approval was supported by ATOMIC/ML39057 showing improved investigator-assessed DFS (HR 0.50).
The US FDA approved atezolizumab (Tecentriq) in combination with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients ≥2 years with Stage III mismatch repair deficient (dMMR) colon cancer.
The FDA also approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) (subcutaneous) with a fluoropyrimidine and oxaliplatin for adults and pediatric patients ≥12 years who weigh ≥40 kg with Stage III dMMR colon cancer. Full prescribing information will be posted on Drugs@FDA.
Supporting evidence
Efficacy and safety were evaluated in ATOMIC/ML39057 (NCT02912559), a multicenter, randomized, open-label, active-controlled trial including 711 adults and 1 pediatric patient with Stage III dMMR colon cancer after complete resection with no evidence of residual lymph node involvement or metastatic disease.
Patients were randomized 1:1 to:
Atezolizumab + mFOLFOX6 for 12 cycles, then atezolizumab monotherapy for 6 months, or
mFOLFOX6 alone for 12 cycles.
Primary outcome was investigator-assessed disease-free survival (DFS): HR 0.50 (95% CI, 0.35–0.73; p=0.0001); median DFS not reached in either arm.
Key safety information (label warnings/precautions)
Includes immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.
The review was conducted under Project Orbis; reviews are ongoing at partner agencies.
Regulatory approval: On Oct 7, 2026, the FDA approved tucatinib (Tukysa) plus trastuzumab and pertuzumab as maintenance therapy for adults with unresectable locally advanced or metastatic HER2-positive breast cancer without progression after induction with trastuzumab/pertuzumab and a taxane. Approval was supported by HER2CLIMB-05 (N=654), showing investigator-assessed PFS improvement (median 24.9 vs 16.3 months; HR 0.64; p<0.0001). OS data were not mature at the time of PFS analysis.
The FDA approved tucatinib (Tukysa; Seagen Inc., a subsidiary of Pfizer) in combination with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction therapy.
Supporting evidence: HER2CLIMB-05 (NCT05132582)
Approval was based on HER2CLIMB-05, a randomized, double-blind, placebo-controlled trial in 654 adults with HER2-positive unresectable locally advanced or metastatic breast cancer with or without brain metastases, who had no investigator-assessed progression after 4–8 cycles of induction trastuzumab + pertuzumab + a taxane.
Patients received tucatinib 300 mg orally twice daily or placebo, with trastuzumab and pertuzumab given intravenously or via a fixed-dose subcutaneous combination (trastuzumab/pertuzumab/hyaluronidase). Patients with hormone receptor–positive disease could continue endocrine therapy. Treatment continued until progression or unacceptable toxicity.
Efficacy
Primary endpoint: PFS by investigator assessment (RECIST v1.1).
Median PFS: 24.9 months (95% CI, 21.3–not reached) with tucatinib vs 16.3 months (95% CI, 12.6–18.7) with placebo; HR 0.64 (95% CI, 0.51–0.80); p<0.0001.
OS was an additional endpoint; data were not mature at the time of PFS analysis.
Safety and dosing highlights
Labeling includes a boxed warning for hepatotoxicity, and warnings/precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function. Recommended dose: tucatinib 300 mg PO BID with trastuzumab and pertuzumab until progression or unacceptable toxicity.
Regulatory approval: On Oct 2, 2026, the FDA approved pirtobrutinib (Jaypirca; Eli Lilly) for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion. Approval was supported by the randomized, open-label BRUIN CLL-313 trial, in which independent review committee–assessed progression-free survival favored pirtobrutinib versus bendamustine plus a rituximab product. Overall survival data were immature at the primary analysis.
The FDA approved pirtobrutinib (Jaypirca; Eli Lilly and Company) for adult patients with previously untreated CLL/SLL with no known 17p deletion. Full prescribing information will be posted on Drugs@FDA.
Evidence base: BRUIN CLL-313 (NCT05023980)
BRUIN CLL-313 was a randomized, open-label, active-controlled trial in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p. Patients were randomized 1:1 to:
Pirtobrutinib (n=141) until disease progression, or
Bendamustine + a rituximab product (n=141) for six cycles.
Efficacy
Primary endpoint: PFS by independent review committee.
Median follow-up for PFS: 28 months
Median PFS: not estimable (NE) with pirtobrutinib vs 33.5 months with control
HR 0.20 (95% CI: 0.11–0.37); p <0.0001
OS was immature at the primary PFS analysis; median OS was not reached in either arm. There were 13 deaths total (pirtobrutinib 3 [2.1%] vs control 10 [7.1%]).
Safety (selected)
Most common (≥20%) non-laboratory adverse reactions: upper respiratory tract infections (27%), rash (22%), COVID-19 (21%). Most common (>10%) grade 3/4 laboratory abnormality: decreased neutrophil count. Serious adverse reactions occurred in 28%.
Prescribing information includes warnings/precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.
Dosage
Recommended dose: 200 mg orally once daily until disease progression or unacceptable toxicity.
Regulatory approval: On Sept 24, 2026, the FDA approved belzutifan (Welireg) plus lenvatinib (Lenvima) for adults with advanced renal cell carcinoma with a clear cell component following prior PD-1/PD-L1 inhibitor therapy. Approval was supported by the open-label, randomized LITESPARK-011 trial (n=747), which showed a statistically significant improvement in PFS versus cabozantinib; final OS analysis was not statistically significant. Recommended dosing is lenvatinib 20 mg plus belzutifan 120 mg once daily.
The FDA approved belzutifan (Welireg) in combination with lenvatinib (Lenvima) for adults with advanced renal cell carcinoma with a clear cell component (ccRCC) following a PD-1 or PD-L1 inhibitor.
Supporting evidence: LITESPARK-011 (NCT04586231)
Design/Population: Open-label, randomized, active-controlled trial in 747 patients with locally advanced or metastatic ccRCC progressing on/after PD-1/PD-L1 inhibitor therapy, or within 6 months of completing adjuvant PD-1 therapy.
Arms: Belzutifan + lenvatinib vs cabozantinib (1:1).
Primary outcomes: PFS by blinded independent central review (RECIST v1.1) and OS; ORR was additional.
Efficacy
PFS: Median 14.6 months (95% CI, 11.1–16.6) with belzutifan+lenvatinib vs 10.6 months (95% CI, 9.2–11.1) with cabozantinib; HR 0.74 (95% CI, 0.61–0.89); one-sided p=0.00095.
OS (final): Not statistically significant; median 33.7 vs 28.6 months; HR 0.85 (95% CI, 0.70–1.03).
ORR:53% vs 40%; one-sided p=0.0002.
Safety highlights (label)
Belzutifan includes a boxed warning for embryo-fetal toxicity and warnings/precautions for anemia and hypoxia; for the combination, also cardiac dysfunction. Lenvatinib includes multiple warnings/precautions including hypertension and cardiac dysfunction.
Recommended dosage
Lenvatinib 20 mg + belzutifan 120 mg orally once daily until disease progression or unacceptable toxicity.
Regulatory approval: On September 23, 2026, the FDA approved lirafugratinib (Lyrfigtu; Elevar Therapeutics), a kinase inhibitor, for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma with an FGFR2 gene fusion or other rearrangement. Approval was supported by the single-arm REFOCUS trial (NCT04526106; n=116), which reported an ORR of 46% (95% CI, 36–55) and a median DOR of 11.8 months (95% CI, 7.5–13.0).
The US Food and Drug Administration (FDA) approved lirafugratinib (Lyrfigtu; Elevar Therapeutics, Inc.), a kinase inhibitor, for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement.
Full prescribing information is expected to be posted on Drugs@FDA.
Supporting evidence
Efficacy and safety were evaluated in REFOCUS (NCT04526106), a multicenter, open-label, single-arm trial enrolling 116 patients with unresectable or metastatic cholangiocarcinoma who were FGFR inhibitor–naïve and had received prior chemotherapy or chemoimmunotherapy. Patients received lirafugratinib 70 mg orally once daily until disease progression or unacceptable toxicity.
Primary efficacy endpoints were objective response rate (ORR) and duration of response (DOR) per independent review committee (RECIST v1.1). Reported outcomes:
ORR: 46% (95% CI, 36–55)
Median DOR: 11.8 months (95% CI, 7.5–13.0)
Safety and dosing highlights
The label includes warnings/precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity. The recommended dose is 70 mg once daily until progression or unacceptable toxicity.
Regulatory pathway
The review used the RTOR pilot program and Assessment Aid; the application received priority review and had breakthrough therapy and orphan drug designations.
Research news: The US National Cancer Institute (NCI) and Cancer Research UK (CRUK) highlighted their Cancer Grand Challenges initiative, a global, interdisciplinary program co-founded in 2020 to tackle persistent, large-scale barriers in cancer prevention, detection, and treatment. The program supports international teams with time and resources to pursue high-risk ideas, and includes a “Future Leaders” component for early-career researchers. Initial teams were announced in 2022, with additional cohorts in 2024 and 2026.
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NCI and CRUK outline Cancer Grand Challenges initiative
Type: Research news (not a regulatory approval) Date: September 21, 2026
NCI and Cancer Research UK (CRUK) described progress and structure of Cancer Grand Challenges, a global cancer research initiative co-founded in 2020 to address fundamental questions that single investigators, institutions, or countries cannot readily solve.
The program is positioned to tackle enduring scientific barriers underlying prevention, detection, and treatment—such as why some tumors become aggressive, and what enables treatment resistance or metastatic spread—through international, interdisciplinary teams with flexibility and resources to pursue “bold ideas” that could open new paths in oncology.
Satish Gopal, MD, MPH (NCI acting deputy director for scientific strategy and development; director, Center for Global Health), stated that NCI and CRUK are “uniquely positioned” to lead this effort and emphasized the US commitment to innovation via international collaboration.
The initiative builds on earlier approaches to stimulate unconventional thinking, including NCI’s Provocative Questions Initiative (2011) and CRUK’s Grand Challenge initiative. According to Dinah Singer, PhD (emeritus NCI deputy director for scientific strategy and development), both efforts aimed to push the community toward novel approaches to long-standing problems.
Program timeline: the first partnership-supported teams were announced in 2022, with additional teams in 2024 and 2026. The program also invests in Future Leaders, providing training, mentorship, and collaboration opportunities for early-career researchers.
Regulatory approval: On Sept 18, 2026, the FDA approved imlunestrant (Inluriyo) plus abemaciclib (Verzenio) for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer (FDA-authorized test required) after progression on at least one line of endocrine therapy. The companion diagnostic Guardant360 CDx was also approved. Approval was supported by EMBER-3, where benefit was reported as concentrated in the ESR1-mutated population; OS data were immature at interim analysis.
The FDA approved imlunestrant (Inluriyo) in combination with abemaciclib (Verzenio) for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. Inluriyo and Verzenio are manufactured by Eli Lilly and Company.
The FDA also approved Guardant360 CDx as a companion diagnostic to identify ESR1 mutations for treatment with imlunestrant plus abemaciclib.
Evidence base
Efficacy was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial (n=874) in ER-positive/HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor (alone or with a CDK4/6 inhibitor). Patients eligible for a PARP inhibitor were excluded. Patients were randomized 1:1:1 to imlunestrant, investigator’s choice endocrine therapy (fulvestrant or exemestane), or imlunestrant + abemaciclib.
The major endpoint for the combination was investigator-assessed PFS (RECIST v1.1), comparing combination vs imlunestrant monotherapy. The overall-population PFS comparison was statistically significant, but FDA noted benefit was only observed in the ESR1-mutated population.
In an exploratory ESR1-mutated subgroup (n=159), PFS HR was 0.53 (95% CI, 0.35–0.80); median PFS was 11.1 vs 5.5 months (combination vs imlunestrant alone). ORR was 35% vs 15%. OS data were immature at interim analysis (35% deaths in ESR1-mutated patients).
Key safety and dosing highlights
Imlunestrant label: warning for embryo-fetal toxicity. Abemaciclib label: warnings for diarrhea, neutropenia, ILD/pneumonitis, hepatotoxicity, venous thromboembolism, and embryo-fetal toxicity.
Recommended doses: imlunestrant 400 mg PO once daily (empty stomach) plus abemaciclib 150 mg PO twice daily (with or without food) until progression or unacceptable toxicity.
