CurrentCareSourcePolicy N/A

UTILIZATION MANAGEMENT MEDICAL POLICY

CareSource utilization management medical policy for medical-benefit coverage of Opdivo Qvantig (nivolumab and hyaluronidase-nvhy) specifying recommended prior authorization, approved indications (FDA-approved and other uses with supportive evidence), explicit limitations of use (not for combination with ipilimumab/Yervoy for listed indications), dosing regimens, approval durations, and conditions not recommended for approval.

Policy Summary

PayerCareSource

PolicyUTILIZATION MANAGEMENT MEDICAL POLICY

Policy CodePolicy N/A

Change TypeEarly annual revisions and multiple additions/revisions across indications

Effective Date

Next Review Date

Key ActionPrior authorization is recommended and approval is only recommended if the patient meets the specified indication- and dosing-specific criteria; document required prior treatments and biomarkers and ensure Opdivo Qvantig is not prescribed in combination with Yervoy.

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POLICY UPDATE CHANGES

Added Appendiceal to Colon/Rectal indication and added POLE/POLD1 mutation positive as an approval option; added prior chemotherapy/unresectable/metastatic/neoadjuvant options and explicit prohibition of combination with Yervoy for that indication.

Hepatocellular carcinoma criteria revised to remove prior sorafenib requirement and add liver-confined unresectable or extrahepatic/metastatic disease ineligible for transplant/resection or locoregional therapy; removed requirement for monotherapy following Opdivo+Yervoy.

Policy lists multiple FDA-approved and supportive-evidence indications and dosing regimens for Opdivo Qvantig (various cancers).

Added polymerase epsilon/delta mutation positive tumor as an approval option for colon, rectal, or appendiceal cancer.

Added requirement that Opdivo Qvantig will NOT be used in combination with Yervoy for multiple indications including colon, melanoma, renal cell carcinoma, hepatocellular carcinoma, and others.

Removed requirement that hepatocellular carcinoma patients must have been previously treated with sorafenib.

Multiple indications had monotherapy, stage, and prior therapy requirements removed or revised (e.g., melanoma adjuvant/neoadjuvant durations, NSCLC EGFR/ALK restrictions removed).

Added numerous new conditions of approval across multiple rare tumor types (ampullary adenocarcinoma, anal carcinoma, biliary tract cancers, etc.).

25+Covered indications (FDA & supportive evidence)

1 yrTypical approval duration (many indications)

3Dosing frequency options

15+Tumor types with revisions/added approvals

multipleCombination prohibition added

Coverage Summary & Policy Statement

Opdivo Qvantig (nivolumab and hyaluronidase‑nvhy) is a subcutaneous formulation of the PD‑1 inhibitor nivolumab intended as a substitute for IV nivolumab where labeled. The policy aligns coverage with FDA‑approved and guideline‑supported indications (including NCCN-related guidance) for multiple solid tumors while noting a key limitation: Opdivo Qvantig is not indicated for use in combination with ipilimumab (Yervoy). The policy stance is covered_with_criteria — prior authorization is required, prescribing should be by or in consultation with an oncologist or appropriate specialist, and approvals are time‑limited and contingent on meeting the specific clinical criteria and dosing described below. Continued approvals require ongoing documentation that the patient continues to meet the criteria.

Policy Statement / Prior Authorization

Callout: Prior Authorization Required — Prior authorization is required for medical benefit coverage of Opdivo Qvantig. Approval is recommended only when the patient meets the detailed indication‑specific criteria and dosing in this policy. Prescriber requirement: must be prescribed by or in consultation with a physician who specializes in the treated condition. Requests for dosing outside the regimens documented in this policy will be reviewed case‑by‑case by a clinician (Medical Director or Pharmacist). Approvals are provided for the duration noted in each indication; when duration is given in months, 1 month = 30 days.

Approval Criteria (historical revisions summarized): The policy includes indication‑specific authorization criteria reflecting FDA approvals and limitations (notable limitation: not for use with Yervoy/ipilimumab), dosing regimens (e.g., 600 mg/10,000 U q2w, 900 mg/15,000 U q3w, 1200 mg/20,000 U q4w where applicable), and duration of approval (commonly 1 year or the duration stated for the indication). Criteria require adult patients (≥18 years) unless otherwise specified, documented tumor biomarkers when required (e.g., MSI‑H/dMMR or POLE/POLD1 where applicable), prior chemotherapy exposure when indicated (examples: fluoropyrimidine, oxaliplatin, irinotecan or regimens such as FOLFOX or CapeOX), disease stage (unresectable, advanced, recurrent, or metastatic as applicable), and explicit statement that Opdivo Qvantig will not be used in combination with Yervoy for indications where that limitation applies. The policy also allows extension of approvals if the patient continues to meet criteria and clinical benefit is documented.

Operational notes: Because Opdivo Qvantig received accelerated approvals for some indications based on response rate and duration of response, continued coverage may be contingent upon verification of clinical benefit from confirmatory trials per FDA guidance. Prescribers and providers should document prior lines of therapy, relevant biomarker testing results, treatment intent (neoadjuvant, adjuvant, or metastatic setting), and the selected dosing schedule to support authorization.

Initial Therapy Criteria — FDA-Approved Indications

FDA-Approved Indications - Colon, Rectal, or Appendiceal Cancer

Approve for 1 year if the patient meets ALL of the following (A, B, C, D, and E):

Colon, Rectal, or Appendiceal Cancer

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Biomarker status (ONE required)
- MSI-H / dMMR: The tumor is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
- POLE/POLD1 mutation:

Other Uses with Supportive Evidence

Other Uses with Supportive Evidence (selected examples)

Approve for 1 year if the patient meets the listed all/one criteria for each disease:

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Dosing Options & Authorization Durations

Dosing Options (general repeated across indications)

Approve ONE of the following dosing regimens:

Dosing Options

Option A: 600 mg nivolumab and 10,000 units hyaluronidase administered subcutaneously no more frequently than once every 2 weeksq2w
Option B: 900 mg nivolumab and 15,000 units hyaluronidase administered subcutaneously no more frequently than once every 3 weeksq3w
Option C: 1,200 mg nivolumab and 20,000 units hyaluronidase administered subcutaneously no more frequently than once every 4 weeks

Unproven / Not Recommended for Approval

Conditions Not Recommended for Approval

Coverage not recommended for circumstances not listed in the Recommended Authorization Criteria

Conditions Not Recommended for Approval: Coverage is not recommended for indications or situations not explicitly listed in the Recommended Authorization Criteria

Provider Actions, Documentation & Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is recommended for medical-benefit coverage. Approval is recommended only if the patient meets the policy’s specified criteria for the listed indication and dosing.

Documentation Required

Specialist Prescriber Requirement

Opdivo Qvantig must be prescribed by or in consultation with a physician who specializes in the condition treated (oncologist); approval requires documentation that the prescriber is an oncologist or that an oncologist was consulted.

Applicable Codes & Dosing Regimens

Dosing regimens (described as mg and hyaluronidase units)mixed

600 mg nivolumab + 10,000 units hyaluronidase	Subcutaneous administration no more frequently than once every 2 weeks
900 mg nivolumab + 15,000 units hyaluronidase	Subcutaneous administration no more frequently than once every 3 weeks
1,200 mg nivolumab + 20,000 units hyaluronidase	Subcutaneous administration no more frequently than once every 4 weeks

Referenced drug productsmixed

Opdivo	nivolumab (intravenous infusion) referenced as Opdivo and Opdivo Qvantig
Yervoy	ipilimumab (intravenous infusion) referenced as combination restriction
Cabometyx	cabozantinib tablets referenced in renal cell carcinoma combination removal

These entries describe regimen options and clinical prior‑authorization criteria and are not mappings to billing codes (HCPCS/NDC). Claims and billing should follow payer‑specific HCPCS/NDC guidance; providers should refer to the billing and coding instructions elsewhere in the policy for claims submission details.

Clinical Evidence, Guidance & Definitions

Evidence considerations include the regulatory status that some Opdivo Qvantig indications were granted under accelerated approval based on overall response rate (ORR) and duration of response (DOR), with continued approval potentially contingent on confirmatory trials. Guideline alignment notes that NCCN guidance states Opdivo Qvantig can be substituted for IV nivolumab, and the guidance also documents the limitation that Opdivo Qvantig is not indicated for use with ipilimumab (Yervoy) for many indications.

Revision History & Material Changes

01/08/2025revised

02/12/2025revised

added

Multiple disease-specific approval criteria and dosing options were added across the policy.

Policy Summary

PayerCareSource

PolicyUTILIZATION MANAGEMENT MEDICAL POLICY

Policy CodePolicy N/A

Change TypeEarly annual revisions and multiple additions/revisions across indications

Effective Date

Next Review Date

SourceLink

On This Page

The tumor is polymerase epsilon/delta (POLE/POLD1) mutation positive

C) Prior therapy or disease status (ONE required)

Prior chemotherapy: Patient has tried chemotherapy (examples: fluorouracil (5-FU), capecitabine, oxaliplatin, irinotecan, or adjunctive regimens such as FOLFOX)
Unresectable/advanced/metastatic: Patient has unresectable, advanced, or metastatic disease
Neoadjuvant use: Medication is used for neoadjuvant therapy

D) Combination restriction: The medication will NOT be used in combination with Yervoy (ipilimumab intravenous infusion)

E) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist

FDA-Approved Indications - Esophageal and Esophagogastric Junction Cancer

Approve for the duration noted if the patient meets ALL of the following (A, B, and C):

Esophageal and Esophagogastric Junction Cancer

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Approve for up to 1 year if ONE of the following (i, ii, or iii)
- i) Adjuvant after neoadjuvant chemo: Patient has completely resected esophageal or esophagogastric junction cancer with residual pathologic disease AND medication is used as monotherapy for adjuvant treatment
- ii) First-line unresectable advanced/metastatic ESCC: Medication is used first-line in combination with fluoropyrimidine- and platinum-containing chemotherapy for unresectable advanced or metastatic esophageal squamous cell carcinoma
  Examples of fluoropyrimidine and platinum agents provided in policy
- iii) Advanced/metastatic or monotherapy after chemo: Patient has advanced or metastatic disease AND medication is used as monotherapy following fluoropyrimidine- and platinum-containing chemotherapy or as prior therapy
C) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist
D) Combination restriction: The medication will NOT be used in combination with Yervoy (ipilimumab intravenous infusion)

FDA-Approved Indications - Gastric / GEJ / Esophageal Adenocarcinoma

Approve for 1 year if criteria met:

Gastric / GEJ / Esophageal Adenocarcinoma

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Disease status: Patient has advanced or metastatic disease
C) Combination therapy: Medication is used in combination with fluoropyrimidine- and platinum-containing chemotherapy
Examples of fluoropyrimidine and platinum agents provided in policy
D) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist

FDA-Approved Indications - Head and Neck Squamous Cell Carcinoma

Approve for 1 year if the patient meets ALL of the following (A, B, C, and D):

Head and Neck Squamous Cell Carcinoma

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Disease type and status (ONE required)
- Non-nasopharyngeal disease: Patient has non-nasopharyngeal disease
- Nasopharyngeal with advanced disease: Patient has nasopharyngeal disease AND recurrent, unresectable, oligometastatic, or metastatic disease
C) Disease extent: Patient has recurrent, unresectable, oligometastatic, or metastatic disease
D) Combination restriction: The medication will NOT be used in combination with Yervoy (ipilimumab intravenous infusion)
E) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist

FDA-Approved Indications - Hepatocellular Carcinoma

Approve for 1 year if the patient meets ALL of the following (A, B, C and D):

Hepatocellular Carcinoma

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Disease extent (ONE required)
- Liver-confined unresectable: Liver-confined, unresectable disease and deemed ineligible for transplant
- Extrahepatic/metastatic ineligible: Extrahepatic/metastatic disease and deemed ineligible for resection, transplant, or locoregional therapy
C) Combination restriction: The medication will NOT be used in combination with Yervoy (ipilimumab intravenous infusion)
D) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist

FDA-Approved Indications - Melanoma

Approve for the duration noted if the patient meets ALL of the following (A, B, C, and D):

Melanoma

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Treatment setting (ONE required)
- Unresectable/advanced/metastatic: Unresectable, advanced, or metastatic disease — approve for 1 year
- Neoadjuvant treatment — approve for up to 3 months
- Adjuvant therapy — approve for up to 1 year of treatment (total)
C) Combination restriction: The medication will NOT be used in combination with Yervoy (ipilimumab intravenous infusion)
D) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist

FDA-Approved Indications - Non-Small Cell Lung Cancer (NSCLC)

Approve for the duration noted if the patient meets ALL of the following (A, B, and C):

Non-Small Cell Lung Cancer (NSCLC)

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
Approval scenarios (first-line, subsequent, neoadjuvant/adjuvant, maintenance)
- First-line or continuation maintenance (tumor negative for actionable mutations): Patient has recurrent, advanced, or metastatic disease AND the tumor is negative for actionable mutations (no EGFR exon 19 deletion or L858R, ALK, RET, or ROS1 rearrangements) — approve 1 year
- First-line or subsequent therapy with tumor mutation positive: Patient has recurrent, advanced, or metastatic disease AND tumor positive for one of: EGFR exon 20 mutation, ERBB2 (HER2) mutation, NTRK1/2/3 gene fusion, MET exon 14 skipping mutation, NRG1 gene fusion, or BRAF V600E
- Neoadjuvant/adjuvant setting (resectable disease): Patient has resectable disease (tumors ≥ 4 cm or node positive) AND medication used in combination with platinum-doublet chemotherapy for neoadjuvant therapy (neoadjuvant approval up to 4 months) AND adjuvant after complete resection following neoadjuvant Opdivo or Opdivo Qvantig — approve for 1 year total
- Subsequent therapy: Patient has recurrent, advanced, or metastatic disease AND patient has received targeted therapy for the specific actionable mutation (when applicable)
B) Combination restriction: The medication will NOT be used in combination with Yervoy (ipilimumab intravenous infusion)
C) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist

FDA-Approved Indications - Renal Cell Carcinoma

Approve for 1 year if the patient meets ALL of the following (A, B, C, and D):

Renal Cell Carcinoma

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Disease status: Patient has advanced, relapsed, or metastatic disease
C) Combination restriction: The medication will NOT be used in combination with Yervoy (ipilimumab intravenous infusion)
D) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist
E) Combination option note: Opdivo Qvantig may be used in combination with cabozantinib (Cabometyx) for first-line treatment of adults with advanced disease (per indication text)

FDA-Approved Indications - Urothelial Carcinoma

Approve for 1 year if the patient meets BOTH of the following (A and B):

Urothelial Carcinoma

A) Age: Patient is ≥ 18 years of ageAge ≥ 18
B) Prescriber requirement: Medication is prescribed by or in consultation with an oncologist
Indication contexts (ONE required)
- Received anti-angiogenic therapy: Advanced disease who have received anti-angiogenic therapy, as monotherapy
- Adjuvant high risk: Adjuvant treatment for patients at high risk of recurrence after radical resection, as monotherapy
- Progression after platinum: Locally advanced or metastatic disease with progression during or following platinum-containing chemotherapy, as monotherapy
- First-line cis/gem combination: First-line unresectable or metastatic disease in combination with cisplatin and gemcitabine
- Progression within 12 months: Locally advanced or metastatic disease with progression within 12 months of neoadjuvant/adjuvant platinum-containing chemotherapy, as monotherapy

Approval criteria generally require patients to be ≥ 18 years of age. Standard authorization durations for many indications are 1 year; neoadjuvant approvals are commonly shorter (examples: up to 3 months for certain melanoma neoadjuvant uses, up to 4 months for NSCLC neoadjuvant), and adjuvant approvals are often limited to 1 year (total) where specified. The policy also states that when an approval duration is authorized in months, 1 month = 30 days. Requests for dosing outside the documented dosing regimens will be reviewed case-by-case by a clinician (Medical Director or Pharmacist).

Documentation Required

Prior Treatment / Biomarker Documentation

Providers must document prior therapies and tumor biomarker status where required by the indication (examples in the policy include prior chemotherapy or targeted therapy and biomarkers such as MSI-H/dMMR, POLE/POLD1 mutation, tumor mutational burden–high [TMB‑H], PD‑L1 CPS, and actionable mutations).

Billing Rule

Dosing Outside Policy

Requests for doses outside the established dosing regimens in this policy (600 mg/10,000 units q2w, 900 mg/15,000 units q3w, 1,200 mg/20,000 units q4w) will be considered on a case‑by‑case basis by a clinician (Medical Director or Pharmacist).

Prior Authorization

Use restrictions and combination prohibition

The policy explicitly requires that Opdivo Qvantig NOT be used in combination with Yervoy (ipilimumab intravenous infusion) for multiple listed indications; providers must document the intended regimen and confirm no concurrent Yervoy.

Denial Risk

Combination with Yervoy Prohibited

Coverage may be denied if Opdivo Qvantig is used in combination with Yervoy contrary to the policy’s explicit limitation of use for multiple indications.

Documentation Required

Line of therapy and disease status documentation

Providers must document disease stage and line of therapy where required (examples: unresectable, oligometastatic, metastatic; prior treatments or neoadjuvant/adjuvant context; and molecular status such as POLE/POLD1 positivity when specified).

added

Also added requirement that patient has tried chemotherapy; or has unresectable/advanced/metastatic disease; or is using medication as neoadjuvant therapy.

added

Combination prohibition added as new requirement across several tumor types.

removed

Added new approval options for unresectable liver-confined disease and extrahepatic disease ineligible for transplant/resection and locoregional therapy.

revised

Revisions adjust prior authorization criteria, durations, and permitted settings.

added

These represent expansion of covered indications.

2025-03-26reviewLatest

Policy last reviewed (selected revision) on 03/26/2025 consolidating prior Early Annual Revisions and selected edits.

This policy part includes a material change flag. Recent material edits summarized include additions for colon/rectal/appendiceal indications (including POLE/POLD1 mutation–positive tumors and related prior‑therapy or neoadjuvant options), revisions to hepatocellular carcinoma criteria (removal of prior sorafenib requirement and addition of liver‑confined and extrahepatic/ineligible‑for‑transplant options), addition of explicit prohibitions against combining Opdivo Qvantig with Yervoy across multiple tumor types, and multiple expansions of indications and dosing/authorization scenarios across many tumor types.