Trial Watch No. 18

▸ Oncology

Phase 3 · Oncology — first-line EGFR NSCLC · MEGA-SCALE

Izalontamab Brengitecan (Iza-bren) + Osimertinib vs. Osimertinib ± Chemo in First-Line EGFR-Mutant NSCLC

Sponsor: Bristol-Myers Squibb (via SystImmune partnership)

Phase / Status / Enrollment: Phase 3, randomized, open-label · Not yet recruiting · 850 participants · 103 locations

Timeline: Start September 30, 2026 · Primary completion December 2031

Mechanism: Izalontamab Brengitecan (BMS-986507, “Iza-bren”) is the branded form of BL-B01D1, SystImmune’s EGFR/HER3 bispecific antibody-drug conjugate. Bristol Myers Squibb and SystImmune announced their global collaboration in December 2023, with $800 million upfront and total potential consideration of up to $8.4 billion. The Phase 3 study combines Iza-bren with osimertinib in previously untreated EGFR-mutant NSCLC.

Why it matters: This is a flagship pivotal from one of the largest China-to-global ADC licensing collaborations of its period. A positive result would establish the Iza-bren plus osimertinib combination as a direct first-line challenger in EGFR-mutant NSCLC and materially validate the BMS–SystImmune partnership at Phase 3 scale.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07680790

BMS exact trial page: https://www.bmsclinicaltrials.com/us/en/clinical-trials/NCT07680790

Phase 3 · Oncology — first-line NSCLC · MEGA-SCALE

ABBV-1480 + Chemotherapy vs. Pembrolizumab + Chemotherapy in First-Line Locally Advanced/Metastatic NSCLC

Sponsor: AbbVie

Phase / Status / Enrollment: Phase 3, randomized, open-label, multiregional · Not yet recruiting · 940 participants

Timeline: Start September 22, 2026 · Primary completion December 2029

Mechanism: ABBV-1480 (RC148) is a humanized PD-1/VEGF bispecific antibody licensed by AbbVie from RemeGen outside Greater China. It combines PD-1 checkpoint inhibition with VEGF pathway blockade in a single molecule and is being tested with platinum chemotherapy against pembrolizumab plus chemotherapy.

Why it matters: This is a direct Phase 3 challenge to the pembrolizumab plus chemotherapy backbone in first-line advanced NSCLC. If ABBV-1480 improves outcomes, AbbVie would add a late-stage PD-1/VEGF bispecific to a treatment setting currently anchored by established checkpoint inhibitor combinations.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07756645

AbbVie exact trial page: https://www.abbvieclinicaltrials.com/study/M26-509

Phase 3 · Oncology — mCRPC · B7-H3 ADC · MEGA-SCALE

EMBOLD Prostate-302 · Risvutatug Rezetecan (B7-H3 ADC) vs. Enzalutamide/Abiraterone in mCRPC

Sponsor: GlaxoSmithKline

Phase / Status / Enrollment: Phase 3, randomized · Recruiting · 684 participants

Timeline: Start September 22, 2026 · Primary completion December 2029

Mechanism: Risvutatug Rezetecan (Ris-Rez) is GSK's B7-H3-directed antibody-drug conjugate. Tested in metastatic castration-resistant prostate cancer vs. investigator's choice of second ARPI (enzalutamide or abiraterone + prednisone).

Why it matters: B7-H3 is an increasingly important ADC target across solid tumors. Ris-Rez brings GSK into the late-stage B7-H3 field in mCRPC, alongside other advanced programs such as Merck/Daiichi Sankyo’s ifinatamab deruxtecan. A positive Phase 3 result would strengthen B7-H3 as a clinically validated ADC target in prostate cancer.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07802704

GSK exact trial page: https://www.gsk-studyregister.com/trials/300145

Phase 3 · Oncology — ovarian maintenance · CDH6 ADC · MEGA-SCALE

REJOICE-Ovarian 04 · Raludotatug Deruxtecan (R-DXd) ± Bevacizumab vs. SoC in Non-HRD+ Ovarian Cancer Maintenance

Sponsor: Merck Sharp & Dohme LLC

Phase / Status / Enrollment: Phase 3, randomized, open-label · Recruiting · 802 participants

Timeline: Start September 18, 2026 · Primary completion March 2032

Mechanism: Raludotatug deruxtecan (R-DXd, MK-5909) is Merck's CDH6 (cadherin-6)-directed ADC with a topoisomerase I deruxtecan payload — from the Merck-Daiichi Sankyo collaboration. Tested as maintenance ± bevacizumab in newly diagnosed advanced non-HRD-positive ovarian cancer after first-line platinum chemotherapy.

Why it matters: The non-HRD-positive ovarian cancer population (roughly half of all ovarian patients) has limited maintenance options beyond bevacizumab. PARP inhibitors work best in HRD+ tumors. R-DXd targets CDH6, expressed on ovarian and renal cancers — validated in early trials with response rates ~50% in heavily pretreated ovarian cancer. First-line maintenance Phase 3 is Merck's franchise-scale bet on CDH6 as the next validated ADC target.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07776691

Health Canada exact trial page: https://recherche-essais-cliniques.canada.ca/en/clinical-trial/504360-ovarian-cancer

Phase 3 · Oncology — adjuvant KRAS G12C+ NSCLC

Divarasib vs. Investigator's Choice of Immunotherapy or Observation in Resected Stage II-III KRAS G12C+ NSCLC

Sponsor: Hoffmann-La Roche

Phase / Status / Enrollment: Phase 3, randomized, open-label · Recruiting · 400 participants · 19 sites

Timeline: Start September 30, 2026 · Primary completion January 2032

Mechanism: Divarasib (GDC-6036) is Roche/Genentech's next-generation covalent KRAS G12C inhibitor. Tested in patients with resected Stage II-III KRAS G12C-positive NSCLC vs. investigator's choice of adjuvant immunotherapy (pembrolizumab or nivolumab) or observation.

Why it matters: This is a Phase 3 test of KRAS G12C inhibition in the adjuvant NSCLC setting. The strategy follows the broader movement of genotype-directed lung cancer therapy from advanced disease toward curative-intent treatment. A positive readout could expand KRAS G12C testing and targeted treatment into resected disease.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07541170

Roche exact trial page: https://forpatients.roche.com/en/trials/cancer/lung-cancer/a-study-to-evaluate-the-efficacy-and-safety-of-divarasi-70040.html

▸ Cardiometabolic

Phase 3 · Cardiometabolic — obesity flagship · MEGA-SCALE

Once-Weekly Petrelintide vs. Placebo in Adults With Overweight or Obesity

Sponsor: Hoffmann-La Roche

Phase / Status / Enrollment: Phase 3, randomized, double-blind, placebo-controlled · Not yet recruiting · 3,900 participants

Timeline: Start September 30, 2026 · Primary completion December 2028

Mechanism: Petrelintide is Zealand Pharma’s long-acting amylin analog, being co-developed and co-commercialized with Roche under a global collaboration and licensing agreement announced in March 2025. This study evaluates once-weekly petrelintide monotherapy for chronic weight management in adults with overweight or obesity.

Why it matters: Petrelintide gives Roche and Zealand Pharma a differentiated amylin-based entry into a market dominated by incretin therapies. The 3,900-participant Phase 3 tests whether a once-weekly amylin analog can deliver clinically meaningful weight loss with a distinct tolerability and mechanism profile at registrational scale.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07843498

Syfrah exact trial page: https://www.syfrah.com/trial/NCT07843498

Phase 3 · Cardiometabolic — obesity + CV disease · MEGA-SCALE

Once-Weekly Petrelintide vs. Placebo in Overweight/Obesity With Established Cardiovascular Disease

Sponsor: Hoffmann-La Roche

Phase / Status / Enrollment: Phase 3, randomized, double-blind, placebo-controlled · Not yet recruiting · 2,500 participants

Timeline: Start September 30, 2026 · Primary completion July 2030

Mechanism: This companion Phase 3 evaluates petrelintide versus placebo for weight management in adults with overweight or obesity who also have established cardiovascular disease. The registered primary endpoint is percentage change in body weight, making this a weight-management study in a high-risk CVD population rather than a dedicated cardiovascular outcomes trial.

Why it matters: Studying petrelintide in participants with established cardiovascular disease tests the asset in a clinically high-risk population that is especially relevant to obesity treatment. Importantly, the registered study is not a MACE-driven cardiovascular outcomes trial; its primary efficacy focus is weight change.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07843472

ClinicalTrials.gg exact trial page: https://clinicaltrials.gg/study/NCT07843472

Phase 3 · Cardiometabolic — obesity (Novo head-to-head vs. semaglutide)

AMAZE 7 · Zenagamtide vs. Semaglutide in Overweight or Obesity

Sponsor: Novo Nordisk A/S

Phase / Status / Enrollment: Phase 3, randomized, double-blind · Recruiting · 650 participants · 43 locations

Timeline: Start September 22, 2026 · Primary completion October 2028

Mechanism: Zenagamtide, also known as amycretin, is Novo Nordisk’s investigational unimolecular GLP-1 and amylin receptor agonist. AMAZE 7 tests once-weekly zenagamtide head-to-head against semaglutide in adults with overweight or obesity.

Why it matters: Novo Nordisk is testing a next-generation dual GLP-1/amylin mechanism directly against semaglutide, its current obesity standard. The head-to-head design makes AMAZE 7 an important internal benchmark for whether zenagamtide can support franchise succession beyond semaglutide.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07668414

DataLookout exact trial page: https://dashboard.datalookout.com/trial/NCT07668414

Phase 3 · Cardiometabolic — obesity + OSA (UBT franchise expansion)

UNISHAPE-OSA-1 · UBT251 in Obese Participants With Moderate-to-Severe Obstructive Sleep Apnea

Sponsor: The United Bio-Technology (Hengqin) Co., Ltd.

Phase / Status / Enrollment: Phase 3, randomized, double-blind, placebo-controlled · Not yet recruiting · 150 participants

Timeline: Start September 18, 2026 · Primary completion September 2028

Mechanism: UBT251 is UBT's GLP-1/glucagon/GIP triple agonist. UNISHAPE-OSA-1 extends the program into obesity + moderate-to-severe OSA in patients not on positive airway pressure therapy — following Lilly's tirzepatide OSA precedent (SURMOUNT-OSA).

Why it matters: UBT251 is expanding rapidly across multiple Phase 3 metabolic indications. UNISHAPE-OSA-1 extends the program into obesity with moderate-to-severe obstructive sleep apnea, a strategically important obesity-comorbidity setting following the clinical validation of incretin-based weight loss in OSA.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07767942

ClinicalTrials.gg exact trial page: https://clinicaltrials.gg/study/NCT07767942

Phase 3 · Cardiometabolic — uncontrolled hypertension (China)

Baxdrostat 2mg vs. Placebo in Chinese Participants With Uncontrolled Hypertension on ≥2 Antihypertensives

Sponsor: AstraZeneca

Phase / Status / Enrollment: Phase 3, randomized, double-blind, placebo-controlled · Not yet recruiting · 286 participants

Timeline: Start September 30, 2026 · Primary completion February 2028

Mechanism: Baxdrostat is AZ's aldosterone synthase (CYP11B2) inhibitor — inherited via the 2023 CinCor Pharma acquisition ($1.8B). This is the China-specific Phase 3 for the uncontrolled hypertension indication on top of 2+ antihypertensives excluding diuretics.

Why it matters: Baxdrostat is one of the highest-value CV assets in the AZ pipeline post-CinCor deal. This Chinese Ph3 opens China as a global regulatory pathway alongside AZ's US/EU pivotal programs. Uncontrolled hypertension is the largest addressable cardiometabolic market by patient count — a definitive aldosterone-synthase inhibitor readout has franchise-shifting potential.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07686120

Veeva exact trial page: https://ctv.veeva.com/study/a-phase-iiib-study-to-investigate-the-effect-of-baxdrostat-in-chinese-participants-with-uncontrolled

▸ Immunology & Respiratory

Phase 2 · Immunology — dual CD20/BCMA CAR-T (lupus nephritis)

C-CAR168 · Autologous Dual Anti-CD20/BCMA CAR-T in Refractory Lupus Nephritis

Sponsor: AbelZeta Inc.

Phase / Status / Enrollment: Phase 2, single-arm · Not yet recruiting · 50 participants

Timeline: Start September 30, 2026 · Primary completion December 2028

Mechanism: C-CAR168 is AbelZeta's autologous dual-antigen CAR-T therapy targeting both CD20 (mature B cells) and BCMA (plasma cells). Tested in lupus nephritis refractory to standard therapy.

Why it matters: Fourth autoimmune CAR-T program in four editions (Myeloid Tx CRT-402 in vivo CAR-T Ed 16, CRISPR Therapeutics CTX112 allo Ed 17, now C-CAR168 dual autologous). Dual CD20/BCMA CAR-T is a mechanistic evolution — targeting both mature B cells AND plasma cells addresses the residual autoantibody-producing cell reservoir that CD19-only CAR-T can miss. First dual-target autoimmune CAR-T Phase 2 in lupus.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07729826

UniteRare exact trial page: https://www.uniterare.org/trials/NCT07729826

Phase 3 · Respiratory — COPD long-term extension · MEGA-SCALE

Tilrekimig Long-Term Safety and Efficacy Extension in Moderate-to-Severe COPD

Sponsor: Pfizer

Phase / Status / Enrollment: Phase 3, open-label extension · Not yet recruiting · 1,360 participants

Timeline: Start September 21, 2026 · Primary completion May 2034

Mechanism: This is a long-term open-label extension of Pfizer’s tilrekimig in moderate-to-severe COPD. Tilrekimig is also being developed across other Type 2 inflammatory diseases, including asthma and atopic dermatitis, creating a broader multi-indication Phase 3 program.

Why it matters: Second respiratory OLE in two editions (following Sanofi's lunsekimig COPD OLE, Ed 17). Pfizer and Sanofi are building parallel long-term safety databases at 1,360-pt and 1,508-pt scale, respectively, for their competing Type 2 respiratory franchises. Long-term safety data is what determines commercial success in a chronic maintenance category with 20-year use horizons.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07839884

Eichor exact trial page: https://eichor.com/study/NCT07839884

Phase 3 · Immunology — Nemolizumab in Chinese AD

Nemolizumab vs. Placebo in Chinese Adults With Moderate-to-Severe Atopic Dermatitis

Sponsor: Galderma R&D

Phase / Status / Enrollment: Phase 3, randomized, double-blind, placebo-controlled · Not yet recruiting · 240 participants

Timeline: Start September 28, 2026 · Primary completion September 2027

Mechanism: Nemolizumab (Nemluvio, Galderma's IL-31 receptor A antagonist, approved 2024 for AD and prurigo nodularis) tested in Chinese patients with moderate-to-severe atopic dermatitis for the China regulatory pathway.

Why it matters: This China bridging study extends Galderma’s nemolizumab development into a major atopic dermatitis market. It also adds another differentiated Type 2 inflammatory mechanism to the competitive AD landscape, alongside IL-4/13 and other emerging pathways.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07762833

Syfrah exact trial page: https://www.syfrah.com/trial/NCT07762833

▸ Neurology

Phase 3 · Neurology — Rett Syndrome

Bionetide in Girls and Women With Rett Syndrome

Sponsor: Biomed Industries, Inc.

Phase / Status / Enrollment: Phase 3, randomized, double-blind, placebo-controlled · Recruiting · 210 participants · 18 sites

Timeline: Start September 30, 2026 · Primary completion September 2027

Mechanism: Bionetide is Biomed Industries' investigational neuroprotective peptide for Rett Syndrome — an X-linked MECP2 mutation disorder in females causing severe neurodevelopmental disability. Tested vs. placebo in a 210-patient global Phase 3.

Why it matters: Rett syndrome has one approved disease-targeted therapy, trofinetide, while substantial unmet need remains. Bionetide provides a late-stage alternative mechanism in a rare neurodevelopmental disease where new treatment options remain limited.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT06840496

AllClinicalTrials exact trial page: https://www.allclinicaltrials.com/study/NCT06840496

Phase 3 · Neurology — chronic spinal cord injury (first Ph3 in years)

RESTORE · NVG-291 vs. Placebo in Adults With Chronic Spinal Cord Injury

Sponsor: NervGen Pharma

Phase / Status / Enrollment: Phase 3, randomized, double-blind, placebo-controlled multicenter · Not yet recruiting · 150 participants · 18 sites

Timeline: Start September 23, 2026 · Primary completion July 14, 2027

Mechanism: NVG-291 is NervGen's protein tyrosine phosphatase sigma (PTPσ) modulator — a peptide designed to promote axonal regeneration and neural plasticity in chronic spinal cord injury. Tested vs. placebo in adults with chronic SCI.

Why it matters: RESTORE brings a novel neural-repair mechanism into Phase 3 for chronic spinal cord injury, an area with no approved neuroregenerative therapy. A positive result would provide pivotal evidence for PTPσ modulation as a therapeutic strategy in chronic CNS injury.

Verified Sources

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT07799532

Veeva exact trial page: https://ctv.veeva.com/study/a-trial-investigating-the-efficacy-and-safety-of-nvg-291-in-subjects-with-chronic-spinal-cord-injury

Signal Convergence

Five patterns across the September 16–30 window

1. Petrelintide scales into franchise-sized Phase 3 development. The two Roche-sponsored petrelintide studies profiled in this edition total 6,400 participants across general obesity/overweight and established cardiovascular disease populations. The program is based on Zealand Pharma’s amylin analog under the Roche–Zealand global co-development and co-commercialization collaboration.

2. Three ADC pivotals and a PD-1/VEGF bispecific move in parallel. BMS advances Iza-bren, GSK advances Ris-Rez, and Merck/Daiichi Sankyo advance R-DXd across lung, prostate, and ovarian cancer. AbbVie adds a separate first-line NSCLC challenge with the PD-1/VEGF bispecific ABBV-1480.

3. Mutation-directed therapy crosses into curative-intent adjuvant. Roche's Divarasib Phase 3 in resected KRAS G12C+ Stage II-III NSCLC is the first adjuvant KRAS G12C inhibitor pivotal. Follows the EGFR playbook (osimertinib ADAURA) and ALK playbook (alectinib ALINA) — mutation-directed therapy now spans the entire disease continuum from metastatic to resectable.

4. Metabolic Phase 3 programs are expanding into comorbidity-specific and head-to-head settings. UBT251 UNISHAPE-OSA-1 tests a triple agonist in obesity with moderate-to-severe OSA, while AMAZE 7 puts Novo Nordisk’s zenagamtide directly against semaglutide. In parallel, petrelintide is being tested in people with established cardiovascular disease, broadening late-stage metabolic competition beyond weight loss alone.

5. Autoimmune CAR-T is moving toward mechanistic diversification. AbelZeta’s C-CAR168 targets both CD20 and BCMA in refractory lupus nephritis, extending the autoimmune CAR-T sequence tracked in recent Trial Watch editions toward dual-antigen strategies.

Underlying truth: late-stage competition is intensifying simultaneously in metabolic disease and precision oncology. This window combines franchise-scale obesity studies, multiple ADC pivotals, a PD-1/VEGF bispecific head-to-head, autoimmune CAR-T, and late-stage neurology programs.

Continue Tracking

Trial Watch is KITSA's clinical intelligence layer.

Edition 19 (October 1–15, 2026) drops on October 15.

On Verification

Final source audit completed for Edition 18 on September 30, 2026. Each profiled trial is linked to its canonical ClinicalTrials.gov record plus one exact trial-specific secondary page or sponsor study page. WHO ICTRP query links, generic sponsor homepages, broad trial-search portals, and “search this term” notes have been removed. Trial status, start-date, and key enrollment fields were rechecked against current registry or sponsor-specific sources before this file was finalized.