Momentum in Advanced Prostate Cancer: What the Last Month Delivered for Men Living with Metastatic Disease

Special Report: 

Informed Prostate Cancer Support Group  •  San Diego, CaliforniaIPCSG Member Newsletter  •  Research & Treatment Update September 2026  •  Educational Use Only

For men living with metastatic castration-resistant prostate cancer (mCRPC) and their families, the weeks from mid-August through mid-September 2026 brought a steady drumbeat of encouraging news. Radioligand therapy continued its march across every stage of metastatic disease, a new generation of immune-based "T-cell engagers" moved deeper into late-stage testing, precision medicine pressed earlier into the disease course, and a landmark government action promised real relief on the price of one of our most-used pills. This report gathers those developments in one place, with an eye toward what they mean for men whose disease no longer responds to hormone therapy alone.

1. Radioligand therapy: now a tool for every stage

The biggest story of the season carried straight into September. On July 31, 2026, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan), given together with an androgen-receptor pathway inhibitor (ARPI), for men with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC).¹ With this decision, Pluvicto can now be used across all stages of PSMA-positive metastatic prostate cancer, a change Novartis says nearly doubles the number of men who may benefit.^1,2

The approval rests on the Phase III PSMAddition trial. Adding Pluvicto to standard therapy reduced the risk of the cancer worsening or of death by 28% at the primary analysis, with an updated analysis showing a 33% reduction and an early trend toward longer overall survival (hazard ratio 0.80), though final survival data are still maturing.² Serious (grade 3 or higher) side effects occurred in about 51% of men receiving the combination versus 43% on standard care alone; dry mouth, fatigue, nausea, hot flushes and anemia were the most common.²

What this means for mCRPC Pluvicto's roots are in mCRPC, and that remains its central role. It is approved after an ARPI but before chemotherapy (since March 2025), and after chemotherapy (since 2022). Real-world data from the Novartis PRECISION platform reported a median progression-free survival of roughly 13.5 months in taxane-naïve mCRPC, and suggested men do better when Pluvicto is started after a single ARPI rather than waiting through several.³ The practical lesson for our members: if you carry PSMA-positive mCRPC, ask whether a PSMA-PET scan and radioligand therapy belong earlier in your plan, not only as a last resort.

The next wave of radioligands aimed at mCRPC

Behind Pluvicto, a deep pipeline is taking shape, much of it pointed squarely at castration-resistant disease:

• 67Cu-SAR-bisPSMA (Clarity Pharmaceuticals) holds FDA fast track designation for PSMA-positive mCRPC after an ARPI. Final results from its Phase 1/2a SECuRE trial were expected in September 2026, making this one to watch in the coming weeks.⁴
• TRE-515 (Trethera), a first-in-class oral enzyme inhibitor, received fast track designation in combination with Pluvicto for PSMA-positive mCRPC, a strategy meant to make radioligand therapy work harder.⁵
• Actinium-225 "alpha" therapies are advancing on several fronts. UCLA's Phase 2 ANDROMEDA trial is directly comparing alpha-emitting 225Ac-PSMA-617 with beta-emitting 177Lu-PSMA-617 alongside targeted radiation for recurrent disease.⁶ Industry programs from Bayer (an actinium-225 PSMA agent in early mCRPC testing) and Eli Lilly (the ACCEL study of [225Ac]-PSMA-62) are exploring whether the more powerful alpha particle can help men who progress after lutetium-based treatment.^7,8

2. A new front opens: T-cell engagers and immune-based options

Immunotherapy has historically underperformed in prostate cancer, but a class of drugs called bispecific T-cell engagers—which grab a cancer-cell target with one arm and a patient's own T-cells with the other—is changing that outlook for mCRPC.

• Xaluritamig (Amgen), which targets a prostate protein called STEAP1, has moved into two Phase 3 trials in mCRPC: XALience (xaluritamig plus abiraterone versus the physician's choice of therapy in men who have not yet had chemotherapy, enrolling roughly 750 patients with overall survival as the main goal) and XALute (in men who have already received a taxane).^9,10
• Pasritamig (Johnson & Johnson), a first-in-class engager aimed at kallikrein-2 (KLK2), earned FDA fast track designation for mCRPC in early September 2026—among the freshest items in this report. Early Phase 1 data showed it was well tolerated, with fewer than 10% of men experiencing low-grade cytokine release reactions, a median radiographic progression-free survival near 7.9 months, and a PSA drop of 50% or more in about 42% of patients at the recommended dose.¹¹
• Two additional targeted agents advanced this summer: BNT324/DB-1311, an antibody-drug conjugate against the B7-H3 protein, and ONCT-534, a dual-action androgen-receptor inhibitor—both received fast track designation for mCRPC that has stopped responding to standard ARPIs.^12,13

Why "fast track" matters to patients Fast track designation does not mean a drug is approved or proven. It is an FDA program that speeds development for therapies addressing serious conditions with unmet need, allowing closer FDA collaboration and eligibility for accelerated approval. For men following the pipeline, it is a signal that regulators see promise—and an invitation to ask your oncologist whether a relevant trial is enrolling near you.

3. Precision medicine pushes earlier—and the case for genetic testing

Several of the season's headlines involved matching treatment to a man's tumor genetics. While much of this activity is in hormone-sensitive disease, it directly shapes the road ahead for men who will later face mCRPC.

• Talazoparib (Talzenna) plus enzalutamide (Xtandi): This PARP-inhibitor combination, already approved for HRR-mutated mCRPC, is now under FDA priority review to move earlier, into HRR-mutated metastatic hormone-sensitive disease, based on the Phase 3 TALAPRO-3 trial of 599 men. A decision is expected in the fourth quarter of 2026.^14,15
• Capivasertib (Truqap) plus abiraterone: Approved in June 2026 for men with PTEN-deficient metastatic hormone-sensitive disease (the CAPItello-281 trial). Roughly one in four men with this cancer carry the PTEN change that the drug is designed to exploit.¹⁵
• Niraparib plus abiraterone (Akeega): Continues to define a role for PARP inhibition in BRCA-driven disease, reinforced by the AMPLITUDE data reported earlier in 2026.¹⁶

Action item for men with mCRPC Nearly every one of these advances is unlocked by a lab test. If you have not had germline (inherited) genetic testing and tumor genomic testing for HRR genes such as BRCA1/BRCA2, and for PTEN status, this is the month to ask. These results decide whether PARP inhibitors, capivasertib, and several trials are open to you.

4. Access and cost: a landmark government action

One of the most consequential developments this month came not from a laboratory but from Washington. Under the Inflation Reduction Act's Medicare Drug Price Negotiation Program, the Centers for Medicare & Medicaid Services (CMS) reached a negotiated price for enzalutamide (Xtandi), one of the most widely used oral drugs in advanced prostate cancer. The negotiated price reflects roughly a 48% reduction from the list price and takes effect January 1, 2027.^17,18

The stakes are real for our members: Xtandi's list price has run above $14,500 per month, and because it is a daily pill it falls on the Medicare Part D drug benefit.¹⁷ For 2026, Part D also caps annual out-of-pocket drug costs at $2,100, another provision of the same law.¹⁸ Drug manufacturers have challenged the negotiation program in federal court, so the policy landscape continues to evolve; the negotiated prices, however, are moving forward on schedule.¹⁷

On the supply side, the FDA also approved an updated (ETM) new drug application for Camcevi (leuprolide) 42-mg injection, a form of the hormone-lowering therapy (ADT) that underpins treatment at every stage of the disease.¹⁹

5. What it all means for men with mCRPC

Taken together, this month's news reinforces a theme our expert speakers have stressed for several years: mCRPC is no longer a "one-size-fits-all" diagnosis. Today's care blends four pillars—androgen-receptor pathway inhibitors, biomarker-driven and bone-targeted therapy, chemotherapy, and a fast-growing set of targeted and radioligand approaches—chosen according to a man's prior treatments, imaging, and tumor biology.²⁰ The direction of travel is clear: effective therapies are moving earlier, PSMA imaging is guiding decisions, and genetics increasingly opens doors that did not exist a year ago.

Questions worth bringing to your care team

• Is my cancer PSMA-positive on PET imaging, and could radioligand therapy fit earlier in my plan?
• Have I had complete germline and tumor genomic testing (BRCA1/2, other HRR genes, PTEN)?
• Am I a candidate for any actively enrolling trial—xaluritamig, pasritamig, a next-generation radioligand, or a PARP/AKT combination?
• How will the 2027 Medicare-negotiated price for enzalutamide and the annual out-of-pocket cap affect my costs?
• Are my bone-protecting agents and supportive care optimized alongside my cancer treatment?

A note to our readers. The information presented herein is gathered from clinical-trial reports, peer-reviewed literature, company and government announcements, and reputable news coverage for the educational benefit of the IPCSG membership. It represents the experience and thoughts of our community and should not be any substitute for medical counsel. Treatment decisions should always be made with your own physician. Drug approvals, trial results, and prices described here are current as of mid-September 2026 and may change. Mention of a company, drug, or trial is not an endorsement.

Sources & Formal Citations

1. Novartis. "FDA approves Pluvicto for PSMA+ metastatic hormone-sensitive prostate cancer (mHSPC)." Media release, July 31, 2026. novartis.com
2. Kansteiner F. "Novartis' Pluvicto leaps ahead into earlier manifestation of prostate cancer." Fierce Pharma, August 3, 2026. fiercepharma.com
3. Novartis. "New real-world data reinforce earlier use of Pluvicto before chemotherapy in mCRPC" (PRECISION platform). Media release, February 24, 2026. novartis.com
4. Shore N (reporting). "FDA grants fast track designation to 67Cu-SAR-bisPSMA for mCRPC." Urology Times, 2026. urologytimes.com
5. "FDA Grants Fast Track Designation to TRE-515 Plus Radioligand Therapy in PSMA+ mCRPC." OncLive, July 2, 2026. onclive.com
6. "Trial to compare 225Ac-PSMA-617 vs 177Lu-PSMA-617 for oligorecurrent prostate cancer" (ANDROMEDA, NCT07150715). Urology Times, June 22, 2026. urologytimes.com
7. ClinicalTrials.gov. "A Study of Actinium-225-macropa-pelgifatamab (BAY3546828) in Advanced mCRPC," NCT06052306. clinicaltrials.gov
8. ClinicalTrials.gov. "[Ac-225]-PSMA-62 in Oligometastatic Hormone-Sensitive and Castration-Resistant Prostate Cancer" (ACCEL), NCT06229366. clinicaltrials.gov
9. "ASCO 2026: XALience — Phase 3 Xaluritamig + Abiraterone vs Investigator's Choice in Chemotherapy-Naïve mCRPC." UroToday, June 1, 2026. urotoday.com
10. ClinicalTrials.gov. "Phase 3 Study of Xaluritamig vs Cabazitaxel or Second ARDT in Progressive mCRPC" (XALute), NCT06691984. clinicaltrials.gov
11. "FDA grants fast track designation to pasritamig for mCRPC." Urology Times, September 2026. urologytimes.com
12. "FDA Fast Tracks Promising New ADC (BNT324/DB-1311) in mCRPC." Targeted Oncology, June 1, 2026. targetedonc.com
13. "FDA grants Fast Track Designation to ONCT-534 for mCRPC." Urology Times, June 29, 2026. urologytimes.com
14. Feldman S. "Prostate Cancer Treatments in the FDA Pipeline: What Could Come Next." CURE, September 4, 2026. curetoday.com
15. ZERO Prostate Cancer. "What's New in Prostate Cancer Treatment? 2026 Research and FDA Approvals." 2026. zerocancer.org
16. "Prostate Cancer at ASCO 2026: Perioperative Intensification, PARP Inhibitors Move Earlier, De-escalation Data" (TALAPRO-3, AMPLITUDE, PROTEUS, A-DREAM). Binaytara Cancer News, July 8, 2026. binaytara.org
17. "Medicare's negotiated 2027 prices reach cancer drugs like Xtandi and Ibrance." September 2026. newsbreak.com; see also "Second Cycle of Medicare Drug Price Negotiations Includes 4 Oncologic Agents," OncLive, 2026. onclive.com
18. Centers for Medicare & Medicaid Services. "New Lower Drug Prices Under the Medicare Drug Price Negotiation Program" (negotiated prices, IPAY 2027). CMS.gov. cms.gov
19. "FDA Approved Camcevi ETM New Drug Application for Prostate Cancer." CURE, September 2026. curetoday.com
20. "A New Therapeutic Era in Metastatic Castration-Resistant Prostate Cancer." Pharmacy Times, 2026. pharmacytimes.com; ASCO. "Systemic Therapy in Patients with mCRPC: Living Guideline, Version 2026.1," J Clin Oncol. ascopubs.org

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Prepared for the IPCSG membership as an educational research summary • September 2026