CurrentEmblemHealthPolicy MG.MM.PH.434

Opdivo Qvantig (nivolumab and hyaluronidase-nvhy) Medical Policy

Clinical coverage criteria, dosing limits, and authorization rules for Opdivo Qvantig for adult oncology indications; applies to EmblemHealth members and providers requesting preauthorization.

Policy Summary

PayerEmblemHealth

PolicyOpdivo Qvantig (nivolumab and hyaluronidase-nvhy) Medical Policy

Policy CodePolicy MG.MM.PH.434

Change TypeRoutine review — no material changes

Effective DateMar 24, 2025

Next Review DateMar 24, 2025

Key ActionSubmit clinical evidence that the member meets criteria when requesting preauthorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 monthsstandard initial authorization length

1,200 mgper-dose medical benefit limit

18+minimum patient age

13 cyclesNSCLC neoadjuvant+adjuvant max

600 mgprimary listed subcutaneous dose

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Coverage Criteria and Indications

Universal Initial Criteria

Covered when ALL of the following universal criteria are met for Initial therapy

Universal Initial Criteria: Patient is at least 18 years of age; AND Patient has not received previous PD-1/PD-L1-directed therapy unless otherwise specified (e.g., switch-therapy with IV nivolumab is an exception); AND Therapy will not be used concomitantly with intravenous nivolumab; AND IV formulation of nivolumab (Opdivo) must be used for patients <80 kg OR for patients requiring the 900 mg/15,000 units dose OR for patients receiving therapy in combination with ipilimumab.

From Initial section

Urothelial Carcinoma (Bladder Cancer)

Urothelial Carcinoma — Covered when ANY of the following apply (in addition to universal criteria)

Urothelial options: Single-agent use for disease that progressed during or following platinum-containing chemotherapy OR progression within 12 months of neoadjuvant or adjuvant platinum-containing therapy; OR single-agent as adjuvant therapy in patients at high risk for disease recurrence after surgical resection (high risk defined as ypT2-ypT4a or ypN+ after neoadjuvant cisplatin, or pT3-pT4a or pN+ for those who did not receive neoadjuvant cisplatin and are ineligible for or refused adjuvant cisplatin); OR combination with cisplatin and gemcitabine as first-line therapy for unresectable or metastatic disease.

Includes high-risk definition

Colorectal Cancer (MSI-H/dMMR)

Colorectal Cancer — Covered when ALL of the following are met (in addition to universal criteria)

CRC MSI-H/dMMR criteria: Patient has MSI-H/dMMR disease as determined by an FDA-approved or CLIA-compliant test; AND Opdivo Qvantig will be used as a single agent; AND used as subsequent therapy for metastatic disease; AND disease has progressed after treatment with a fluoropyrimidine, oxaliplatin and irinotecan regimen.

From CRC section

Gastric, Esophageal, Gastroesophageal Junction Cancer

Gastric/Esophageal/GEJ Cancer — Covered scenarios (in addition to universal criteria)

Gastric/Esophageal/GEJ uses: Single‑agent adjuvant treatment of completely resected esophageal or GEJ cancer with residual pathologic disease after neoadjuvant chemoradiotherapy; OR single‑agent subsequent therapy after prior fluoropyrimidine‑ and platinum‑based chemotherapy for unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) or for advanced/metastatic gastric, GEJ, or esophageal adenocarcinomas; OR used in combination with fluoropyrimidine‑ and platinum‑containing chemotherapy as first‑line therapy for unresectable advanced or metastatic disease.

Includes first‑line and adjuvant contexts

Squamous Cell Carcinoma of the Head and Neck

Head and Neck Squamous Cell Carcinoma — Covered when ALL of the following are met (in addition to universal criteria)

SCCHN criteria: Used as single‑agent therapy; AND patient has metastatic disease with disease progression on or after platinum‑based therapy; AND disease is not of the nasopharynx.

From SCCHN section

Hepatocellular Carcinoma

Hepatocellular Carcinoma — Covered when ALL of the following are met (in addition to universal criteria)

HCC criteria: Used as a single agent; AND patient was previously treated with sorafenib following prior treatment with nivolumab/ipilimumab.

From HCC section

Renal Cell Carcinoma

Renal Cell Carcinoma — Covered when ANY of the following are met (in addition to universal criteria)

RCC options: Single‑agent first‑line therapy for intermediate or poor risk disease following prior nivolumab+ipilimumab combination therapy; OR subsequent therapy after prior anti‑angiogenic therapy; OR used in combination with cabozantinib (Cabometyx) as first‑line therapy for advanced disease (dosing: 600 mg q2w or 1,200 mg q4w; when combined with cabozantinib 40 mg once daily, up to a maximum of 2 years).

From RCC section and dosing guidance

Cutaneous Melanoma

Cutaneous Melanoma — Covered when ANY of the following are met (in addition to universal criteria)

Melanoma uses: Single‑agent first‑line therapy for unresectable or metastatic disease; OR subsequent therapy after prior nivolumab/ipilimumab combination therapy for unresectable or metastatic disease; OR adjuvant treatment for stage IIB, IIC, stage III, or metastatic disease after complete resection (adjuvant dosing: treat up to 1 year for adjuvant therapy; standard recurring doses 600 mg q2w or 1,200 mg q4w).

From Melanoma section and dosing guidance

Non-Small Cell Lung Cancer (NSCLC)

Non‑Small Cell Lung Cancer — Covered when ANY of the following are met (in addition to universal criteria)

NSCLC options: Single‑agent for metastatic disease as subsequent therapy after platinum‑based chemotherapy (patients with EGFR or ALK aberrations should have progressed on targeted therapies first); OR in combination with platinum‑doublet chemotherapy as neoadjuvant therapy for resectable tumors ≥4 cm or node‑positive disease, with option to continue single‑agent adjuvant therapy post‑surgery (neoadjuvant: 900 mg q3w with platinum‑doublet x3 cycles then adjuvant 1,200 mg q4w up to 13 cycles; metastatic dosing: 600 mg q2w or 1,200 mg q4w).

From NSCLC section and dosing guidance

General coverage conditions and dosing-aligned criteria

Coverage is provided when dosing, indication, and duration align with the listed disease‑specific schedules and administrative requirements.

Dose and administration match policy: Use of Opdivo Qvantig must follow the subcutaneous dosing and administration instructions specific to the cancer type (examples: RCC, melanoma, metastatic NSCLC, SCCHN, urothelial, hepatocellular, esophageal, gastric/GEJ as listed). NSCLC neoadjuvant: 900 mg with platinum‑doublet q3w x3 cycles then 1,200 mg q4w post‑surgery up to 13 cycles. Standard recurring doses include 600 mg q2w or 1,200 mg q4w where specified.

See dosing sections

Route and administration location: Subcutaneous administration only (abdomen or thigh) by a healthcare professional over 3–5 minutes; Opdivo Qvantig dosing and administration differ from IV nivolumab and the IV formulation must be used for the 900 mg/15,000 units dosing to prevent wastage.

From dosing notes

Duration limits for adjuvant therapy: Adjuvant therapy: generally treat until disease recurrence or unacceptable toxicity for up to 1 year for specified indications; select combination regimens may allow up to 2 years maximum as noted in regimen‑specific dosing guidance.

Therapy with Opdivo Qvantig must not be used concomitantly with intravenous nivolumab. The policy requires the IV formulation of nivolumab be used instead for specific clinical situations: when the patient weighs 80 kg, when the prescribed dose is the 900 mg / 15,000 units regimen, or when nivolumab is given in combination with ipilimumab.

The prescribing information lists a 900 mg / 15,000 units dose; however, to avoid product wastage and because dosing and administration differ between products, the policy requires use of the intravenous nivolumab formulation for that dose. Opdivo Qvantig is a distinct, subcutaneous formulation with different dosage and administration instructions and therefore should not be used in place of IV nivolumab for the 900 mg / 15,000 units regimen.

Patients who have previously received PD-1/PD-L1–directed therapy are generally ineligible for coverage of Opdivo Qvantig unless a specific exception is documented. One noted exception is when Opdivo Qvantig is used as a switch-therapy with intravenous nivolumab; other exceptions must be explicitly stated in the policy or supported by documentation.

Opdivo Qvantig is approved only as a subcutaneous product and must be administered per its labeled route and instructions. Use of Opdivo Qvantig outside the subcutaneous route (for example, as an IV product) or failure to follow the specified dosing and administration (abdomen or thigh, administered by a healthcare professional over 3–5 minutes) is not supported by this policy; the IV nivolumab formulation should be used when IV dosing is required.

Covered Regimens and Combination Therapies

Regimen	Indication	Dose / Schedule	Coverage status
Opdivo Qvantig + cabozantinib (Cabometyx)
First-line therapy for advanced renal cell carcinoma
Opdivo Qvantig: 600 mg (10,000 units) every 2 weeks OR 1,200 mg (20,000 units) every 4 weeks; when given in combination: Opdivo Qvantig as above administered with cabozantinib 40 mg once daily (without food), up to a maximum of 2 years of therapy.
Covered

Regimen	Indication	Dose / Schedule	Coverage status
Opdivo Qvantig in combination with cisplatin and gemcitabine
First-line therapy for unresectable or metastatic urothelial carcinoma
900 mg (15,000 units) every 3 weeks with cisplatin and gemcitabine on the same day for up to 6 cycles, then transition to 600 mg (10,000 units) every 2 weeks OR 1,200 mg (20,000 units) every 4 weeks until disease progression or unacceptable toxicity.
Covered

Setting	Dose options	Notes	Coverage status
Renal cell carcinoma (monotherapy or combination)
600 mg (10,000 units) every 2 weeks OR 1,200 mg (20,000 units) every 4 weeks
When combined with cabozantinib 40 mg once daily (without food), therapy is allowed up to a maximum of 2 years.
Covered

Phase	Dose / Schedule	Number of cycles / Duration	Coverage status
Adjuvant (post-surgery)
1,200 mg (20,000 units) every 4 weeks as single-agent Opdivo Qvantig
Up to 13 cycles (maximum approximately 12 months)
Covered

Regimen	Indication	Dose / Schedule	Coverage status
Opdivo Qvantig in combination with fluoropyrimidine- and platinum-containing chemotherapy
Gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma (combination regimens)
600 mg (10,000 units) every 2 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks OR 900 mg (15,000 units) every 3 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks; administered per combination schedule, up to a maximum of 2 years. For adjuvant therapy in esophageal and GEJ: treat up to 1 year (until disease recurrence or unacceptable toxicity).
Covered

Line of Therapy Specifications

first-line | second-line | salvage

Line of therapy examples: Indication applicability includes first‑line, subsequent therapy, adjuvant and neoadjuvant contexts depending on cancer type (e.g., urothelial: first‑line in combination with cisplatin/gemcitabine or subsequent single‑agent after platinum; CRC: subsequent therapy for metastatic MSI‑H/dMMR after specific chemotherapy; RCC: first‑line or subsequent depending on combination or prior therapies; NSCLC: first‑line neoadjuvant in combination with chemo or subsequent single‑agent after platinum therapy).

Top‑level line‑of‑therapy node

neoadjuvant | adjuvant

Neoadjuvant NSCLC: Neoadjuvant/adjuvant NSCLC: 900 mg with platinum‑doublet chemotherapy q3w for 3 cycles (same day), then surgery and adjuvant single‑agent Opdivo Qvantig 1,200 mg q4w after surgery for up to 13 cycles (maximum ~12 months).

Neoadjuvant | Adjuvant top‑level node

first-line

First‑line designation: First‑line use is defined per cancer‑specific sections and includes use in combination regimens where noted (e.g., urothelial carcinoma with cisplatin+gemcitabine; RCC with cabozantinib), following the dosing schedules specified for first‑line regimens.

First‑line top‑level node

Biomarker and Test Evidence Requirements

inv-35: MSI-H/dMMR — Determined by FDA-approved or CLIA-compliant test

RequirementMSI-H/dMMR must be determined by an FDA-approved or CLIA-compliant test

Indication contextRequired for coverage in colorectal cancer as subsequent therapy

Therapy settingUse as single-agent therapy when criteria met

inv-36: MSI — e.g., initial MSS and subsequent MSI-H (document testing history requirements)

Documentation of testing historyPolicy allows re-initiation consideration when re-biopsy shows a change in actionable mutation (e.g., initial MSS and subsequent MSI-H)

Re-initiation triggerChange from MSS to MSI-H on subsequent biopsy may make patient eligible to re-initiate PD-directed therapy

EvaluationCases with changed biomarker status will be evaluated on a case-by-case basis and require documentation

Coding, Dosing Limits, and Billing

Dosing/HCPCS limitsHCPCS

HCPCS

Max Units: 1,200 mg/20,000 units every 4 weeks (per-dose medical benefit limit)

Applicable Procedure CodesHCPCS

J9999	Not otherwise classified, antineoplastic drugs.
C9399	Unclassified drugs or biologics (hospital outpatient use only)

Applicable NDCsNDC

00003-6120-xx

Opdivo Qvantig single-dose vial providing 600 mg nivolumab and 10,000 units hyaluronidase per 5 mL (120 mg/ 2,000 units per mL)

Included ICD-10 Diagnoses (representative; full list present in document)ICD-10Covered

C00.0	Malignant neoplasm of external upper lip
C34.01	Malignant neoplasm of right main bronchus
C34.02	Malignant neoplasm of left main bronchus

inv-19: Per-dose maximum — 1,200 mg/20,000 units every 4 weeks

Per-dose maximum1,200 mg / 20,000 units every 4 weeks

Billing unitMaximum units listed under HCPCS dosing limits (medical benefit)

ApplicabilityPer-dose limit applies to subcutaneous Opdivo Qvantig dosing scenarios unless otherwise specified

inv-20: NSCLC neoadjuvant/adjuvant duration — Maximum of twelve (12) months (13 cycles) for NSCLC neoadjuvant/adjuvant treatment

Maximum durationMaximum of twelve (12) months (13 cycles) for NSCLC neoadjuvant/adjuvant treatment

Neoadjuvant dosing limitNeoadjuvant-only authorization may be limited to three (3) neoadjuvant doses when not followed by adjuvant treatment

Neoadjuvant + adjuvant combinationWhen neoadjuvant followed by adjuvant, authorization may be for up to 4 neoadjuvant doses and 13 adjuvant doses

Prior Authorization, Documentation, and Billing Actions

Prior Authorization

Clinical Evidence Submission

Prior authorization is required. The treating physician or primary care provider must submit clinical evidence that the member meets the criteria for the requested therapy. Failure to provide this documentation will prevent proper review for preauthorization or may result in post-payment denial.

Treating physician or primary care provider must submit clinical evidence for preauthorization or post-payment review.
If documentation is not submitted, EmblemHealth cannot properly review the request.

Documentation Required

Administration and Formulation Documentation

Documentation must support use of the subcutaneous Opdivo Qvantig formulation (NDC 00003-6120-xx). Include specific details on dose, route (subcutaneous), administration site (abdomen or thigh), and that administration will be performed by a healthcare professional over 3–5 minutes. Note the product-specific dosing/administration differences compared with IV nivolumab.

Applicable NDC: 00003-6120-xx (Opdivo Qvantig single-dose vial)
Opdivo Qvantig is for subcutaneous use only (abdomen or thigh) and administered by a healthcare professional over 3–5 minutes
Include dose and route in documentation to justify use of the subcutaneous formulation

Step Therapy

Prior PD‑1/PD‑L1 Therapy Limitation

Prior PD‑1/PD‑L1 therapy is restricted. Patient must not have previously received PD‑1/PD‑L1‑directed therapy (examples: atezolizumab, pembrolizumab, durvalumab, avelumab, cemiplimab, dostarlimab, nivolumab/relatlimab, retifanlimab, toripalimab, tislelizumab, etc.) unless an exception applies (for example, switch‑therapy to intravenous nivolumab as specified). Requests for members with prior PD‑1/PD‑L1 exposure must include supporting clinical rationale and documentation to demonstrate eligibility under any exception.

Prior PD‑1/PD‑L1 therapy is not allowed unless an exception is documented (e.g., permitted switch‑therapy with IV nivolumab where noted)
Provide documentation of prior therapy history and clinical rationale if seeking approval despite prior PD‑1/PD‑L1 exposure
Re‑initiation may be allowed in certain relapse scenarios (e.g., relapse ≥ 6 months after discontinuation) when criteria are met

Definitions and Product Description

inv-30: Opdivo Qvantig is a programmed death receptor-1 (PD-1) blocking antibody (nivolumab) combined with an endoglycosidase (hyaluronidase-nvhy) indicated for multiple adult cancers.

Drug classProgrammed death receptor-1 (PD-1) blocking antibody (nivolumab) co-formulated with an endoglycosidase (hyaluronidase-nvhy)

Indications (adults)Colorectal, esophageal, gastric/GEJ, head and neck SCC, hepatocellular carcinoma, melanoma, NSCLC, renal cell carcinoma, urothelial carcinoma

Combination formulationNivolumab combined with hyaluronidase-nvhy enables subcutaneous administration as Opdivo Qvantig

inv-31: Opdivo Qvantig — A subcutaneous formulation of nivolumab co-formulated with hyaluronidase, for administration in the abdomen or thigh by a healthcare professional

FormulationSubcutaneous formulation of nivolumab co-formulated with hyaluronidase (Opdivo Qvantig)

Administration route and sitesSubcutaneous use only in the abdomen or thigh

Administration requirementsAdministered by a healthcare professional over 3–5 minutes

Background and Scope

Opdivo Qvantig is a co-formulation of nivolumab (a programmed death receptor-1 [PD-1] blocking antibody) with hyaluronidase-nvhy that enables subcutaneous administration. The policy covers multiple adult oncology indications—such as colorectal (MSI-H/dMMR), esophageal/gastric/GEJ, head and neck squamous cell carcinoma, hepatocellular carcinoma, cutaneous melanoma, non-small cell lung cancer (including neoadjuvant/adjuvant use), renal cell carcinoma, and urothelial carcinoma—when the listed clinical criteria, dosing, and duration requirements are met. Opdivo Qvantig is administered subcutaneously in the abdomen or thigh by a healthcare professional over 3–5 minutes, and its dosing schedules (for example, 600 mg q2w, 900 mg q3w, or 1,200 mg q4w in select indications) must align with the policy’s indication-specific regimens and limits.

Policy Summary

PayerEmblemHealth

PolicyOpdivo Qvantig (nivolumab and hyaluronidase-nvhy) Medical Policy

Policy CodePolicy MG.MM.PH.434

Change TypeRoutine review — no material changes

Effective DateMar 24, 2025

Next Review DateMar 24, 2025

Key ActionSubmit clinical evidence that the member meets criteria when requesting preauthorization.

SourceLink

On This Page

up to 1 year or up to 2 years as specified

From dosing guidance

Re-initiation eligibility: Patients who relapse ≥ 6 months after discontinuation, patients who progress ≥ 6 months after completing adjuvant therapy, patients with change in actionable mutation on re‑biopsy (e.g., initial MSS then MSI‑H) and other specific relapse scenarios may be eligible to re‑initiate PD‑directed therapy; documentation required for case‑by‑case evaluation.

From Notes