HCPCS
J1326
1 unit = 2 mg
Phase 1
Identify what you're billing
Vyloy is first-in-class. The CLDN18.2 IHC test result is the eligibility gate.
About Vyloy (zolbetuximab-clzb) FDA label + Astellas 2025–2026
First-in-class chimeric IgG1 monoclonal antibody that binds the extracellular domain of claudin 18 isoform 2 (CLDN18.2) on gastric tumor cells, triggering antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
Vyloy (generic name: zolbetuximab-clzb) is a chimeric IgG1 monoclonal antibody manufactured by Astellas Pharma US, Inc. (Northbrook, IL). It is the first FDA-approved therapy targeting claudin 18.2 (CLDN18.2), a tight-junction protein selectively expressed on gastric epithelial cells and frequently retained or re-expressed on gastric and gastroesophageal junction (GEJ) adenocarcinoma cells. Binding triggers immune-mediated tumor cell killing via ADCC and CDC.
Vyloy was FDA-approved on October 18, 2024 (BLA 761365) for first-line treatment of adults with HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma whose tumors are CLDN18.2-positive (defined as ≥75% of viable tumor cells demonstrating moderate-to-strong [2+/3+] membranous CLDN18 staining on the VENTANA CLDN18 (43-14A) IHC assay), in combination with a fluoropyrimidine + platinum-containing chemotherapy regimen (mFOLFOX6 or CAPOX).
Approval was based on two parallel global phase 3 trials: SPOTLIGHT (Vyloy + mFOLFOX6 vs placebo + mFOLFOX6) and GLOW (Vyloy + CAPOX vs placebo + CAPOX), both demonstrating statistically significant improvements in progression-free survival and overall survival in the CLDN18.2-positive HER2-negative population. Both trials defined the ≥75% 2+/3+ threshold used in the FDA label.
Vyloy is administered as a 2–3 hour IV infusion. Premedicate with antiemetics
(nausea and vomiting are the most common adverse events, particularly with the loading dose). Reduce
infusion rate or interrupt for grade 2 nausea/vomiting; permanently discontinue for grade 3 or 4
infusion-related reactions per FDA label.
Single-source product. Vyloy has no FDA-approved biosimilar in the U.S. as of May 2026
and is unlikely to face biosimilar competition before 2030s. All zolbetuximab claims bill under J1326
with Astellas NDCs only.
Vyloy in the HER2-negative gastric cancer landscape FDA labels + NCCN 2025–2026
First-line therapy for advanced gastric / GEJ adenocarcinoma is now biomarker-driven. Vyloy occupies the CLDN18.2-positive HER2-negative niche; PD-1 inhibitors + chemo cover PD-L1-positive disease; Herceptin + chemo covers HER2-positive disease.
| Therapy | HCPCS | Biomarker gate | Line | Combo |
|---|---|---|---|---|
| Vyloy (zolbetuximab-clzb) | J1326 |
CLDN18.2 ≥75% 2+/3+ AND HER2-negative | 1L | + mFOLFOX6 OR + CAPOX |
| Herceptin (trastuzumab) + biosimilars | J9355 (Q5) |
HER2-positive (IHC 3+ or IHC 2+ ISH-positive) | 1L | + cisplatin / capecitabine or 5-FU |
| Keytruda (pembrolizumab) | J9271 |
PD-L1 CPS ≥1 (HER2-neg) OR any HER2+ when added to trastuzumab | 1L | + 5-FU + cisplatin (HER2-neg) OR + trastuzumab + chemo (HER2+) |
| Opdivo (nivolumab) | J9299 |
Approved 1L irrespective of PD-L1 (regimen-restricted), but benefit concentrated in PD-L1 CPS ≥5 | 1L | + fluoropyrimidine + platinum |
| Cyramza (ramucirumab) | J9308 |
None (post-progression) | 2L+ | Monotherapy OR + paclitaxel (post-platinum) |
| Enhertu (trastuzumab deruxtecan) | J9358 |
HER2-positive | 2L+ | Monotherapy (post-trastuzumab) |
Vyloy's clinical niche is the CLDN18.2-positive / HER2-negative tumor. Approximately
38–40% of HER2-negative gastric/GEJ adenocarcinomas meet the CLDN18.2 ≥75% 2+/3+ threshold per
SPOTLIGHT + GLOW screening data. For tumors that are both CLDN18.2-positive AND PD-L1 CPS ≥1,
either Vyloy + chemo OR Keytruda + chemo is a valid first-line choice — NCCN does not currently
rank one over the other. Tumors that are CLDN18.2-negative are not Vyloy candidates regardless of any
other biomarker status.
Biomarker testing strategy. Best practice is reflex testing of all newly-diagnosed
advanced gastric/GEJ adenocarcinoma for HER2 (IHC/ISH), PD-L1 (CPS), and CLDN18.2 (VENTANA 43-14A IHC)
simultaneously, so the 1L regimen choice can be made on the first oncology visit without sequential
delays. Discuss reflex panel ordering with pathology.
Dosing, CLDN18.2 testing & worked examples FDA label + Astellas billing guide 2026
800 mg/m² loading (Cycle 1) → 600 mg/m² maintenance q3w with mFOLFOX6 or CAPOX. BSA-based dosing — partial-vial waste is the rule.
CLDN18.2 companion diagnostic — eligibility gate
Per FDA label, Vyloy treatment requires confirmation of CLDN18.2-positive status using the VENTANA CLDN18 (43-14A) RxDx Assay (Roche Tissue Diagnostics). The threshold is ≥75% of viable tumor cells demonstrating moderate-to-strong (2+ or 3+) membranous CLDN18 staining. The pathology report must explicitly document:
- The assay used (VENTANA CLDN18 [43-14A] IHC — not a lab-developed test)
- The percentage of viable tumor cells with membranous staining at each intensity level (0, 1+, 2+, 3+)
- The summary determination: CLDN18.2-positive (≥75% 2+/3+) or CLDN18.2-negative
1+ staining does not count toward the 75% threshold. A tumor with 60% 2+/3+ staining
plus 30% 1+ staining is CLDN18.2-NEGATIVE for Vyloy eligibility — the ≥75% threshold applies to
moderate-to-strong (2+/3+) only. Weak (1+) and absent (0) staining are not eligible.
Dosing schedule
| Cycle | Vyloy dose | Schedule | Combo partner |
|---|---|---|---|
| Cycle 1 (Loading) | 800 mg/m² | Day 1 of 21-day cycle | + mFOLFOX6 OR + CAPOX (per regimen schedule) |
| Cycle 2+ (Maintenance, q3w) | 600 mg/m² | Day 1 of each 21-day cycle, q3wk | + mFOLFOX6 OR + CAPOX (default maintenance for both backbones) |
| Cycle 2+ (Maintenance, q2w — mFOLFOX6 alignment) | 400 mg/m² | Day 1 of each 14-day cycle, q2wk | + mFOLFOX6 only (aligns Vyloy to the q2-week FOLFOX backbone; current FDA label option) |
Continue Vyloy + chemotherapy until disease progression or unacceptable toxicity. Premedicate with antiemetics — nausea and vomiting are the most common adverse events (~82% incidence in pivotal trials), particularly with the higher Cycle 1 loading dose. Reduce infusion rate or interrupt for grade 2 nausea/vomiting; permanently discontinue for grade 3 or 4 infusion-related reactions. Per the current FDA label, monitor patients during and for at least 2 hours after each infusion for hypersensitivity / anaphylaxis and infusion-related reactions.
Maintenance options — q3w 600 mg/m² vs q2w 400 mg/m². The current
FDA label (revised June 12, 2025) supports two maintenance schedules: 600 mg/m² every 3 weeks
(the default, used with either CAPOX or mFOLFOX6) and 400 mg/m² every 2 weeks (added to align
Vyloy with the q2-week mFOLFOX6 backbone). The q2w 400 mg/m² option is mFOLFOX6-only. Verify which
schedule was ordered before billing — unit math differs (540 units for q3w 600 mg/m² at
1.8 m² vs 360 units for q2w 400 mg/m² at 1.8 m²) and the q2w schedule means more
infusions per year (about 26 vs about 17), which materially affects annual coverage modeling.
Worked example — Cycle 1 loading (1.8 m² BSA, mFOLFOX6 backbone)
# Eligibility check (before Cycle 1)
HER2 status: NEGATIVE (IHC 1+, ISH not required)
CLDN18.2: 85% tumor cells with 2+/3+ membranous staining (VENTANA 43-14A IHC)
# Calculate dose
Dose: 800 mg/m² × 1.8 m² = 1,440 mg
Units (1 unit = 2 mg): 1,440 / 2 = 720 units J1326
# Vial draw
100 mg single-dose vials only → 1,440 mg / 100 mg = 14.4 vials
Practical draw: 15 × 100 mg = 1,500 mg drawn · 1,440 mg administered
Waste: 60 mg (30 units) → bill on JW line
# Drug claim lines
Line 1 (administered): J1326 · 720 units
Line 2 (waste): J1326 · 30 units · modifier JW
# Admin claim lines
96413 (chemo IV, up to 1 hour) — initial chemo agent
96415 × 2 (each additional hour) — 2–3 hour Vyloy infusion
96417 × n — sequential mFOLFOX6 components (oxaliplatin, leucovorin, 5-FU)
# Drug reimbursement (Q2 2026 ASP+6% = $33.649 per 2 mg unit)
Total billed units: 720 + 30 = 750 units × $33.649 = $25,236.75 (admin + waste both pay)
HER2 status: NEGATIVE (IHC 1+, ISH not required)
CLDN18.2: 85% tumor cells with 2+/3+ membranous staining (VENTANA 43-14A IHC)
# Calculate dose
Dose: 800 mg/m² × 1.8 m² = 1,440 mg
Units (1 unit = 2 mg): 1,440 / 2 = 720 units J1326
# Vial draw
100 mg single-dose vials only → 1,440 mg / 100 mg = 14.4 vials
Practical draw: 15 × 100 mg = 1,500 mg drawn · 1,440 mg administered
Waste: 60 mg (30 units) → bill on JW line
# Drug claim lines
Line 1 (administered): J1326 · 720 units
Line 2 (waste): J1326 · 30 units · modifier JW
# Admin claim lines
96413 (chemo IV, up to 1 hour) — initial chemo agent
96415 × 2 (each additional hour) — 2–3 hour Vyloy infusion
96417 × n — sequential mFOLFOX6 components (oxaliplatin, leucovorin, 5-FU)
# Drug reimbursement (Q2 2026 ASP+6% = $33.649 per 2 mg unit)
Total billed units: 720 + 30 = 750 units × $33.649 = $25,236.75 (admin + waste both pay)
Worked example — Cycle 2+ maintenance (1.8 m² BSA, CAPOX backbone)
# Calculate dose
Dose: 600 mg/m² × 1.8 m² = 1,080 mg
Units (1 unit = 2 mg): 1,080 / 2 = 540 units J1326
# Vial draw
11 × 100 mg vials = 1,100 mg drawn; 1,080 mg administered
Waste: 20 mg (10 units) → bill on JW line
# Claim lines
Line 1 (administered): J1326 · 540 units
Line 2 (waste): J1326 · 10 units · modifier JW
# Schedule (21-day cycle, q3w until progression)
Day 1: Vyloy 1,080 mg + oxaliplatin 130 mg/m² (J9263); capecitabine 1,000 mg/m² PO BID D1–14
Days 2–14: capecitabine continues PO
Days 15–21: rest
Cycle repeats q3wk
Dose: 600 mg/m² × 1.8 m² = 1,080 mg
Units (1 unit = 2 mg): 1,080 / 2 = 540 units J1326
# Vial draw
11 × 100 mg vials = 1,100 mg drawn; 1,080 mg administered
Waste: 20 mg (10 units) → bill on JW line
# Claim lines
Line 1 (administered): J1326 · 540 units
Line 2 (waste): J1326 · 10 units · modifier JW
# Schedule (21-day cycle, q3w until progression)
Day 1: Vyloy 1,080 mg + oxaliplatin 130 mg/m² (J9263); capecitabine 1,000 mg/m² PO BID D1–14
Days 2–14: capecitabine continues PO
Days 15–21: rest
Cycle repeats q3wk
Cycle-1 vs maintenance billing summary
| Cycle | mg/m² | 1.8 m² mg | Units (2 mg/unit) | Drug $ at Q2 2026 |
|---|---|---|---|---|
| C1 loading | 800 | 1,440 | 720 | $24,227.28 |
| C2+ maintenance (q3w, default) | 600 | 1,080 | 540 | $18,170.46 |
| C2+ maintenance (q2w, mFOLFOX6 only) | 400 | 720 | 360 | $12,113.64 |
NDC reference FDA NDC Directory + Astellas billing guide verified May 2026
| NDC | Strength | Package size | Units / vial |
|---|---|---|---|
0469-1326-01 (verify against current Astellas billing guide) |
100 mg lyophilized powder for reconstitution | 1 single-dose vial per carton | 50 units (1 unit = 2 mg) |
0469-1326-03 (verify against current Astellas billing guide) |
300 mg lyophilized powder for reconstitution | 1 single-dose vial per carton | 150 units (1 unit = 2 mg) |
Use the carton-level NDC with the N4 qualifier. Payers expect the 11-digit NDC
(hyphens or no-hyphens by payer) in the 24A shaded area with the N4 qualifier and total quantity drawn
(UN1 for the 100 mg lyophilized vial). Vial-level NDC variants will trigger denial. The 100 mg vial is
single-dose — discard unused portion (single-dose container policy applies, bill JW for waste).
Reconstitution. Per FDA label, reconstitute the 100 mg vial with 10 mL of sterile
water for injection (or the 300 mg vial with 15 mL) to yield a 20 mg/mL stock for the 300 mg vial
(10 mg/mL for the 100 mg vial); confirm against the current prescribing information for the exact
diluent volume per presentation. Dilute the calculated total dose into a 0.9% sodium chloride or 5%
dextrose infusion bag. Use within the labeled in-use stability window when stored at 2–8°C
(refrigerated) or at room temperature. For larger BSA doses, prefer the 300 mg vial to reduce vial
count and JW waste mg.
Phase 2
Code the claim
Chemo admin codes apply (2–3 hour infusion). JW waste is the rule for BSA-based dosing. CLDN18.2 IHC documentation is non-negotiable.
Administration codes CPT verified May 2026
Vyloy is HCPCS chemotherapy-classified. Use chemo admin codes (96413/96415/96417), not therapeutic infusion codes (96365/96366).
| Code | Description | When to use |
|---|---|---|
96413 |
Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug | Primary code for Vyloy. Bill once per encounter for the initial hour of Vyloy infusion. |
96415 |
Chemotherapy administration, IV infusion; each additional hour (List separately) | Add for hours 2 and 3. Vyloy is a 2–3 hour infusion — expect 1–2 units of 96415 per encounter beyond the initial 96413 hour. |
96417 |
Chemo IV infusion, each additional sequential infusion (different drug) | For mFOLFOX6 or CAPOX components. Each sequential chemo agent (oxaliplatin J9263, leucovorin J0640, 5-FU J9190 for mFOLFOX6; oxaliplatin for CAPOX) gets its own 96417 unit. |
96365 / 96366 |
Therapeutic IV infusion (non-chemo) | NOT appropriate for Vyloy. Zolbetuximab is HCPCS chemo-classified; chemo admin codes are correct. |
Typical Cycle 1 day-1 admin claim — Vyloy + mFOLFOX6. Sequence: Vyloy 800 mg/m²
over ~3 hours (96413 × 1 + 96415 × 2), then oxaliplatin 85 mg/m² over 2 hours
(96417 × 1 + 96415 × 1), then leucovorin 400 mg/m² over 2 hours (96417 × 1 +
96415 × 1), then 5-FU 400 mg/m² IV bolus + 2,400 mg/m² over 46 hours via portable pump
(96417 + 96416 for prolonged-infusion initiation). MAC-specific sequencing rules apply.
Modifiers CMS verified May 2026
JW — the default for Vyloy
JW reports the discarded portion of a single-dose vial. Because Vyloy dosing is BSA-based (mg/m²) and vials are 100 mg single-dose, partial-vial waste occurs on most doses unless the calculated mg lands exactly on a 100 mg multiple. JW applies to most J1326 claims. Bill the administered units on the primary line and the wasted units on a separate line with the JW modifier. Both lines pay at ASP+6%.
Worked JW example — Cycle 1 loading (1.8 m² BSA)
# Dose
800 mg/m² × 1.8 m² = 1,440 mg ordered
# Lowest-waste vial draw (100 mg vials only)
15 × 100 mg = 1,500 mg drawn
Administered: 1,440 mg | Discarded: 60 mg
# Convert to units (1 unit = 2 mg)
Administered: 1,440 / 2 = 720 units
Wasted: 60 / 2 = 30 units (JW)
# Claim lines
Line 1: J1326 · 720 units
Line 2: J1326 · 30 units · modifier JW
800 mg/m² × 1.8 m² = 1,440 mg ordered
# Lowest-waste vial draw (100 mg vials only)
15 × 100 mg = 1,500 mg drawn
Administered: 1,440 mg | Discarded: 60 mg
# Convert to units (1 unit = 2 mg)
Administered: 1,440 / 2 = 720 units
Wasted: 60 / 2 = 30 units (JW)
# Claim lines
Line 1: J1326 · 720 units
Line 2: J1326 · 30 units · modifier JW
JZ — only when no waste
JZ applies when the calculated dose equals an exact 100 mg vial multiple (rare for BSA-based dosing). Example: 1.5 m² patient on 800 mg/m² = 1,200 mg = 12 × 100 mg vials, zero waste → JZ applies. One of JZ or JW must be on every J1326 claim per CMS's July 2023 single-dose container policy.
Common error: Omitting the JW waste line. CMS audits routinely catch this — the
wasted drug is reimbursable but must be reported on a separate claim line. Both administered and
discarded units pay at ASP+6%.
Modifier 25 — same-day E/M
Use modifier 25 on the E/M code when a significant, separately identifiable evaluation and management service is performed on the same day as the infusion. Routine pre-infusion clinical assessment is bundled into the chemo admin code.
340B modifiers (JG, TB)
For 340B-acquired Vyloy, follow your MAC's current 340B modifier policy. Hospital outpatient departments billing under OPPS are subject to specific 340B reporting requirements; office-based 340B reporting varies by MAC.
ICD-10-CM FY2026 verified May 2026
FDA indication is locally advanced unresectable or metastatic gastric / GEJ adenocarcinoma. Use the most specific code supported by encounter documentation; pair with secondary metastatic codes (C77–C79) where applicable.
| Site / type | ICD-10 | Notes |
|---|---|---|
| Stomach — cardia (includes GEJ in most payer policies) | C16.0 | Most common for GEJ adenocarcinoma; cardia-region adenocarcinoma |
| Stomach — fundus | C16.1 | Fundus malignancy |
| Stomach — body | C16.2 | Body / corpus malignancy |
| Stomach — pyloric antrum | C16.3 | Antral malignancy |
| Stomach — pylorus | C16.4 | Pyloric malignancy |
| Stomach — lesser / greater curvature | C16.5 / C16.6 | Curvature-specific gastric |
| Stomach — overlapping | C16.8 | When tumor crosses adjacent subsites |
| Stomach — unspecified | C16.9 | Use when site documentation is incomplete; payer-disfavored |
| Lower esophagus / GEJ (alternative) | C15.5 | Some payers accept C15.5 for GEJ tumors centered in the lower esophagus; follow payer guidance — C16.0 is preferred |
| Secondary malignancy — nodal | C77.x | Regional nodes (paired with primary) |
| Secondary malignancy — liver | C78.7 | Common metastatic site for gastric/GEJ |
| Secondary malignancy — peritoneum | C78.6 | Peritoneal carcinomatosis is the most common metastatic pattern in gastric cancer |
| Secondary malignancy — other respiratory / digestive | C78.x | Lung (C78.0x), pleural (C78.2) |
| Secondary malignancy — other site | C79.x | Bone (C79.51), brain (C79.31), other |
ICD-10 alone is not sufficient. PA criteria require: (a) gastric/GEJ adenocarcinoma
ICD-10, (b) documented HER2-negative status (IHC and/or ISH), (c) CLDN18.2-positive result via
VENTANA 43-14A IHC (≥75% 2+/3+), and (d) concurrent fluoropyrimidine + platinum chemotherapy
regimen documented. All four elements must appear in the PA packet.
Site of care & place of service Verified May 2026
Vyloy is typically administered in oncology offices, ambulatory infusion centers (freestanding infusion suites), and hospital outpatient departments. The 2–3 hour infusion plus the mFOLFOX6 / CAPOX backbone is a 5–7 hour day-1 chair time, which is comfortably within outpatient infusion-suite capacity. Major commercial payers run site-of-care UM for high-cost oncology drugs and steer infusion out of HOPD into office or freestanding AIC settings.
| Setting | POS | Claim form | Payer steering |
|---|---|---|---|
| Physician oncology office | 11 | CMS-1500 / 837P | Preferred by commercial UM |
| Freestanding ambulatory infusion suite (AIC) | 49 | CMS-1500 / 837P | Preferred by commercial UM |
| Oncology ASC | 24 | CMS-1500 / 837P | Acceptable |
| Hospital outpatient (on-campus HOPD) | 22 | UB-04 / 837I | Disfavored after first cycles by commercial site-of-care UM |
| Hospital outpatient (off-campus PBD) | 19 | UB-04 / 837I | Disfavored |
| Patient home | 12 | CMS-1500 (home infusion) | Rare for Vyloy; not standard 1L route given chemo backbone |
HOPD allowed for Cycle 1. Some commercial site-of-care policies permit HOPD for the
initial 1–2 cycles to monitor for infusion reactions, then require transition to office or AIC
for maintenance cycles. If the patient must remain in HOPD for clinical reasons (e.g., comorbidities
requiring hospital-level rescue), submit a medical-necessity letter at the SOC review stage.
Claim form field mapping Astellas billing guide 2026
From Astellas Patient Support / AstellasReach Vyloy billing & coding reference.
| Information | CMS-1500 box | Notes |
|---|---|---|
| NPI | 17b | Rendering provider |
| NDC qualifier + 11-digit NDC + UoM + qty | 24A shaded area | N4 + 0469-1326-01 (100 mg vial, verify current NDC) + UN1 + number of vials drawn |
| HCPCS J1326 (administered line) | 24D (drug line) | Administered units only; larger line |
| HCPCS J1326 + JW (waste line) | 24D (waste line) | Wasted units only; almost always present for BSA-based dosing |
| Drug units | 24G | Mg administered ÷ 2 (e.g., 720 units for 1,440 mg Cycle 1 loading at 1.8 m²) |
| CPT 96413 | 24D (admin line) | Chemo IV, up to 1 hour — initial Vyloy infusion |
| CPT 96415 | 24D | Each additional hour beyond initial 60 minutes (2 units typical for 3-hour Vyloy infusion) |
| CPT 96417 | 24D | Each additional sequential chemo agent (oxaliplatin, leucovorin, 5-FU components) |
| ICD-10 | 21 | C16.x (most commonly C16.0 for cardia/GEJ); add C77–C79 secondary metastatic codes |
| PA number | 23 | Required by all major commercial payers (CLDN18.2 IHC + HER2-neg + chemo combo documented) |
Phase 3
Get paid
PA + CLDN18.2 IHC + HER2-neg + chemo backbone documentation is the gate. Astellas Patient Support helps.
Payer policy snapshot Reviewed May 2026
All major payers require PA. CLDN18.2 IHC documentation is the #1 requirement.
| Payer | PA? | Key requirements | Site-of-care UM |
|---|---|---|---|
| UnitedHealthcare Oncology Med Coverage Policy |
Yes | (1) CLDN18.2 IHC report (VENTANA 43-14A, ≥75% 2+/3+); (2) HER2-negative documentation; (3) concurrent mFOLFOX6 or CAPOX regimen; (4) C16.x ICD-10; (5) line-of-therapy = 1L | Aggressive: chemo steered out of HOPD via Optum-managed program |
| Aetna CPB + Medical Drug policies |
Yes | Aligned with NCCN + FDA label; CLDN18.2 IHC ≥75% 2+/3+ via VENTANA 43-14A enforced; HER2-neg documented; combo chemo concurrent PA required | Yes (separate Site-of-Care policy) |
| Cigna Specialty Drug Coverage Policy |
Yes | NCCN + FDA label aligned; CLDN18.2 IHC report required at initial PA and renewal not needed for biomarker (single-test); chemo backbone PA in parallel | Yes |
| BCBS plans Vary by plan |
Yes | Generally aligned with NCCN + FDA label; CLDN18.2 IHC ≥75% 2+/3+ via VENTANA 43-14A enforced across most plans | Plan-specific; most have oncology site-of-care steering |
Step therapy
Vyloy is approved as a first-line regimen, so there is no formal step-therapy ladder ahead of it. However, payers will check that the patient has not previously progressed on any 1L systemic regimen for their advanced disease — line-of-therapy verification matters. For tumors that are both CLDN18.2-positive AND PD-L1 CPS ≥1, some plans require attestation that Vyloy is the chosen regimen (vs Keytruda + chemo) and may require provider-of-choice documentation. Plans do not currently mandate Keytruda + chemo before Vyloy.
NCCN compendium support
Vyloy + fluoropyrimidine + platinum (mFOLFOX6 or CAPOX) is included as a Category 1 recommendation in the NCCN Gastric Cancer guideline for first-line treatment of HER2-negative locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma with CLDN18.2 positivity (≥75% 2+/3+). Off-label NCCN-supported uses are not currently established; coverage hinges on the on-label first-line indication.
Medicare reimbursement CMS Q2 2026 (live)
Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.
Q2 2026 payment snapshot — J1326
Effective April 1 – June 30, 2026 · Based on 4Q25 ASP submissions
ASP + 6%
$33.649
per 2 mg unit
C1 loading dose
$24,227.28
800 mg/m² × 1.8 m² = 1,440 mg
C2+ maintenance
$18,170.46
600 mg/m² × 1.8 m² = 1,080 mg
Wasted drug is reimbursable. Bill the JW line for the discarded portion — both
administered and discarded units pay at ASP+6%. For a Cycle 1 loading dose at 1.8 m² drawn from
15 × 100 mg vials: 750 units total billed (720 administered + 30 waste) =
$25,236.75 drug reimbursement before sequestration.
Sequestration: Approximately 2% reduction applies to actual paid amount, bringing
effective reimbursement to roughly ASP + 4.3% rather than ASP + 6%. ASP updated quarterly by CMS —
next update: July 1, 2026 for Q3.
Coverage
No NCD specific to zolbetuximab. Coverage falls under MAC LCDs for chemotherapy + the generic drug coverage framework. All MACs cover J1326 for the FDA-approved on-label indication with appropriate documentation (CLDN18.2 IHC, HER2-negative, ICD-10 C16.x or applicable, concurrent fluoropyrimidine + platinum chemo regimen). NCCN compendium support is established.
Code history
- J1326 — permanent code, "Injection, zolbetuximab-clzb, 2 mg"; effective July 1, 2025 HCPCS update following the October 18, 2024 FDA approval. From October 2024 through June 2025, zolbetuximab claims used unclassified C9399 (HOPD) or J3490 (office) with manufacturer invoice required for pricing.
Patient assistance — Astellas Patient Support (AstellasReach) Astellas verified May 2026
- Astellas Patient Support (AstellasReach): centralized Astellas oncology access program for Vyloy. Benefits investigation, prior authorization assistance (including CLDN18.2 IHC result coordination with the pathology lab), appeal letter support, copay assistance enrollment for eligible commercially-insured patients, and free product evaluation for uninsured / underinsured patients meeting Astellas's income criteria.
- Vyloy Co-Pay Savings Program: commercial copay support for eligible commercially-insured patients; excludes Medicare, Medicaid, TRICARE, and other federal program patients (federal anti-kickback statute).
- Astellas Patient Assistance Program: free product for uninsured / underinsured patients meeting income thresholds; administered separately from Astellas commercial.
- Foundations (Medicare patients): PAN Foundation, HealthWell Foundation, CancerCare Co-Payment Assistance — verify open gastric cancer funds quarterly (funds open and close throughout the year).
- Web: astellaspatientsupportsolutions.com
Need to model what a specific patient will actually pay after copay assistance, deductible,
coinsurance, and OOP max? Run a CareCost Estimate — J1326
pre-loaded.
Phase 4
Fix problems
Missing CLDN18.2 IHC, HER2+ patient attempted, missing chemo backbone PA, and monotherapy attempt are the top denials.
Common denials & how to fix them
| Denial reason | Common cause | Fix |
|---|---|---|
| #1: CLDN18.2 IHC testing not documented or threshold not met | PA submitted without VENTANA CLDN18 (43-14A) IHC report, or report shows <75% 2+/3+, or non-VENTANA assay used | Submit VENTANA CLDN18 (43-14A) IHC report explicitly showing ≥75% of viable tumor cells with 2+/3+ membranous staining. If a non-VENTANA assay was used, request reflex testing via the original pathology block on the FDA-required assay. PA cannot be approved without this. |
| #2: HER2-positive patient attempted on Vyloy | HER2-positive tumor (IHC 3+ or IHC 2+ ISH-positive) submitted for Vyloy PA | Vyloy is for HER2-NEGATIVE only. Use Herceptin (J9355) + chemo for 1L HER2+ disease, or Enhertu (J9358) in later lines. Resubmit PA on appropriate HER2-targeted regimen. |
| #3: Chemotherapy backbone not documented | Vyloy PA submitted without concurrent mFOLFOX6 or CAPOX regimen documentation | Submit chemo order showing mFOLFOX6 (oxaliplatin + leucovorin + 5-FU) or CAPOX (oxaliplatin + capecitabine). Vyloy is approved ONLY in combination with a fluoropyrimidine + platinum regimen — monotherapy is not FDA-approved. |
| #4: Monotherapy attempted | Vyloy ordered as single-agent therapy | Add fluoropyrimidine + platinum backbone (mFOLFOX6 or CAPOX). Submit concurrent PA for the chemo agents. |
| JW waste line missing | Wasted units not reported on BSA-based claim | Add JW line for discarded units. Both administered and discarded units pay at ASP+6%. CMS audit risk if omitted. |
| Wrong cycle billed (loading vs maintenance) | C1 loading dose units billed for C2+ maintenance encounter, or vice versa | Verify cycle number against chemo order. C1 = 800 mg/m² (720 units at 1.8 m²); C2+ = 600 mg/m² (540 units at 1.8 m²). Resubmit with corrected unit count. |
| Wrong admin code (96365) | Therapeutic IV billed instead of chemo IV | Resubmit with 96413 + 96415 (each additional hour). Zolbetuximab is HCPCS chemo-classified; chemo admin codes are correct. |
| Wrong NDC format (vial-level) | Vial NDC submitted instead of carton NDC with N4 qualifier | Use 11-digit carton NDC with N4 qualifier in 24A shaded area. Confirm current Astellas NDC against the Vyloy billing & coding guide. |
| Site of care (HOPD) | HOPD administration on commercial plan with site-of-care UM after first cycles | Move to office (POS 11) or AIC (POS 49) for maintenance cycles. Submit medical-necessity letter if HOPD required. |
| Line-of-therapy mismatch | Patient previously received any systemic therapy for advanced disease before Vyloy | Vyloy is approved as first-line. Confirm no prior systemic therapy for the metastatic / unresectable setting. Prior adjuvant therapy completed > 6 months before recurrence may still qualify as 1L — verify with payer. |
Frequently asked questions
What is the HCPCS code for Vyloy?
Vyloy (zolbetuximab-clzb) is billed under HCPCS J1326 — "Injection, zolbetuximab-clzb,
2 mg." The unit basis is 1 unit = 2 mg. Convert milligrams to billing units by dividing
by 2: a Cycle 1 loading dose at 800 mg/m² for a 1.8 m² BSA patient = 1,440 mg =
720 units; the maintenance dose at 600 mg/m² for the same patient = 1,080 mg =
540 units.
Which CLDN18.2 IHC assay is required?
The FDA-required companion diagnostic is the VENTANA CLDN18 (43-14A) IHC assay (Roche / Ventana Tissue Diagnostics). It is the only assay the FDA label references for Vyloy eligibility. Lab-developed CLDN18.2 IHC tests, RNA-based assays, and other vendor assays are NOT acceptable substitutes. PA packets that document positivity using a non-VENTANA assay will deny.
What does VENTANA 43-14A interpretation look like in practice?
The pathologist reports the percentage of viable tumor cells with membranous CLDN18 staining at each intensity (0, 1+, 2+, 3+). For Vyloy eligibility, the sum of cells with 2+ AND 3+ membranous staining must be ≥75% of viable tumor cells. The report should explicitly state: "CLDN18.2-positive: >=75% of tumor cells with 2+/3+ membranous staining (VENTANA CLDN18 [43-14A] IHC)" or "CLDN18.2-negative: <75% of tumor cells with 2+/3+ membranous staining."
What does the ≥75% 2+/3+ threshold mean?
At least 75% of the viable tumor cells in the biopsy must show moderate-intensity (2+) or strong-intensity (3+) membranous staining for claudin 18 on the VENTANA 43-14A IHC assay. Cells with weak (1+) or absent (0) staining do not count toward the 75% threshold. A tumor with 60% 2+/3+ staining plus 30% 1+ staining is NOT eligible for Vyloy — only 60% of cells meet the intensity criterion, below the 75% gate. The pathologist must report both the percentage of CLDN18-positive cells and the dominant staining intensity.
What is the Vyloy dosing schedule?
Cycle 1 (loading): 800 mg/m² IV on day 1, combined with mFOLFOX6 or CAPOX. Cycles 2+ (maintenance): per the current FDA label (revised June 12, 2025), two options exist: 600 mg/m² IV q3w on day 1 of each 21-day cycle (default for either backbone) OR 400 mg/m² IV q2w on day 1 of each 14-day cycle (mFOLFOX6 backbone only). Continue until disease progression or unacceptable toxicity. Infuse over approximately 2–3 hours; reduce rate as needed for tolerability. Premedicate with antiemetics — nausea and vomiting are the most common adverse events (~82% incidence in pivotal trials).
Is Vyloy used in HER2-positive gastric cancer?
No. Vyloy is FDA-approved ONLY for HER2-NEGATIVE locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma. HER2-positive disease is treated with Herceptin (trastuzumab, J9355) + chemotherapy, or with Enhertu (trastuzumab deruxtecan, J9358) in later lines. HER2 status documentation (IHC 0 or 1+, or IHC 2+ with FISH-negative) is a required element of every Vyloy PA packet.
Vyloy vs Keytruda + chemo vs Opdivo + chemo — how do I choose?
For HER2-negative locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma, the choice in 1L is biomarker-driven. Vyloy requires CLDN18.2-positivity (≥75% 2+/3+ on VENTANA 43-14A IHC). Keytruda + 5-FU/cisplatin requires PD-L1 CPS ≥1. Opdivo + fluoropyrimidine + platinum is approved 1L (regimen-restricted; benefit concentrated in PD-L1 CPS ≥5). For tumors that are both CLDN18.2-positive AND PD-L1-positive, either Vyloy or a PD-1 inhibitor + chemo is a valid 1L choice. Tumors that are CLDN18.2-negative are not Vyloy candidates regardless of PD-L1 status.
How do I bill the loading vs maintenance dose differently?
Both bill under the same HCPCS — J1326 — at 1 unit per 2 mg. The difference is
only the unit count: Cycle 1 loading at 800 mg/m² yields ~720 units for a 1.8 m² patient;
Cycle 2+ maintenance at 600 mg/m² yields ~540 units for the same patient. Document the cycle
number in the chart so the payer can correlate the higher Cycle 1 dose with the loading regimen. Audit
risk: maintenance billed at loading-dose units (over-billing) or loading billed at maintenance-dose
units (under-billing) are both common errors.
mFOLFOX6 vs CAPOX — how do they bill alongside Vyloy?
Both chemotherapy backbones are FDA-label combination partners and both are NCCN-supported. mFOLFOX6 components: oxaliplatin (J9263), leucovorin (J0640), 5-fluorouracil (J9190), each on a separate claim line. CAPOX components: oxaliplatin (J9263) IV + capecitabine (oral, NDC + J8520 or pharmacy benefit, plan-dependent). Each chemo agent requires its own concurrent PA. Vyloy bills under J1326 as the initial chemo (96413 + 96415 for the 2–3 hour infusion) with the backbone agents as sequential chemo (96417 per agent). Bundling all under a single line is a denial trigger.
What administration CPT codes apply to Vyloy?
CPT 96413 — "Chemotherapy administration, IV infusion technique; up to 1 hour, single
or initial substance/drug" — bills once per encounter for the initial hour of Vyloy. Add CPT
96415 — "each additional hour" — for hours 2 and 3 (Vyloy is a 2–3 hour
infusion). For sequential mFOLFOX6 or CAPOX components on the same day, add CPT 96417
— "each additional sequential infusion (different drug)" — for each subsequent chemo
agent. Do NOT bill 96365/96366 (therapeutic IV); zolbetuximab is chemo-classified.
Is there a hub program for Vyloy?
Yes — Astellas Patient Support (also branded as AstellasReach). The hub provides benefits investigation, prior authorization assistance (including CLDN18.2 IHC result coordination), appeal letter support, copay assistance enrollment for commercially-insured patients, and free product evaluation for uninsured/underinsured patients meeting Astellas's income criteria. For Medicare patients, refer to PAN Foundation, HealthWell Foundation, and CancerCare Co-Payment Assistance — verify open gastric cancer funds quarterly. See Patient assistance section.
Reference
Sources & methodology
Every claim on this page is sourced. Methodology and review history below.
Source documents
- FDA — VYLOY (zolbetuximab-clzb) prescribing information (BLA 761365; label revised June 12, 2025)
- FDA Drugs@FDA — BLA 761365 application history (zolbetuximab-clzb)
- DailyMed — VYLOY search
- Astellas Patient Support (AstellasReach)
- FDA — October 18, 2024 zolbetuximab-clzb approval announcement
- CMS — Medicare Part B Drug ASP Pricing File
- Roche / Ventana — VENTANA CLDN18 (43-14A) RxDx Assay
- SPOTLIGHT trial (Lancet 2024) — zolbetuximab + mFOLFOX6 in CLDN18.2-positive HER2-negative gastric/GEJ
- GLOW trial (Nature Medicine 2024) — zolbetuximab + CAPOX in CLDN18.2-positive HER2-negative gastric/GEJ
- NCCN Clinical Practice Guidelines — Gastric Cancer
- UnitedHealthcare — Oncology Medication Clinical Coverage Policy
- Aetna Clinical Policy Bulletins — Antineoplastic agents
- CMS — JW/JZ modifier policy (CR 12056, eff. July 2023)
Refresh cadence
| Element | Cadence | How it's refreshed |
|---|---|---|
| Medicare ASP pricing | Quarterly | Auto-bound to CareCost ASP layer; updates on CMS file release. |
| Payer policies (UHC, Aetna, Cigna, BCBS) | Semi-annual | Manual review against published payer policy documents. |
| HCPCS / CPT / modifier rules | Annual | Reviewed against CMS HCPCS quarterly files and AMA CPT releases. |
| NDC, dosing, FDA label, companion diagnostic | Event-driven | Tied to manufacturer document version + FDA label revision date. |
Reviewer
Primary-source verified May 22, 2026. BLA number, label revision date, indication,
dosing options (including q2w maintenance), vial strengths (100 mg + 300 mg), companion-diagnostic
requirement, warnings, and HCPCS / ASP+6% pricing all confirmed against the current DailyMed FDA label
(setid e7695a21-abb6-47ac-93f8-0ece5a9c4409, revised June 12, 2025) and the CMS Q2 2026 Part B Drug
ASP Pricing File. Confirm the current NDC for both the 100 mg and 300 mg presentations against the
Astellas Vyloy billing & coding guide before submitting first-time claims. Independent
clinician/coding SME review pending.
Change log
- — Primary-source audit pass. Corrected Vyloy BLA number from 761403 to 761365. Confirmed current DailyMed label revision date as June 12, 2025. Added 400 mg/m² q2w maintenance option (mFOLFOX6 backbone) alongside the default 600 mg/m² q3w schedule, per current FDA label. Added 300 mg single-dose vial presentation alongside the original 100 mg vial. Updated FAQ, dosing schedule, billing summary, NDC table, and reconstitution callout. ASP data: Q2 2026 ($33.649/2 mg unit). Manufacturer source: Astellas Patient Support / AstellasReach 2025–2026 materials. First-in-class anti-claudin 18.2 monoclonal antibody for HER2-negative locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma with CLDN18.2-positivity (≥75% 2+/3+ on VENTANA CLDN18 [43-14A] IHC), in combination with mFOLFOX6 or CAPOX.
Methodology
Every claim on this page is sourced inline. Pricing reflects the current CMS Part B Drug ASP Pricing File. Payer policies are read directly from each payer's published medical/pharmacy policy documents. Indication, dosing, and companion-diagnostic requirements are verified against the current FDA label revision. We do not paraphrase from billing-software vendor blogs.
Found an error? Email hello@carecostestimate.com.