By Counterforce Health Team in Zanzalintinib (XL092) [investigational] —

If Zanzalintinib (XL092) Isn't Approved by Blue Cross Blue Shield in Michigan: Clinical Trial Access & Formulary Alternatives

Quick Answer: Getting Zanzalintinib (XL092) Coverage in Michigan

Zanzalintinib (XL092) is investigational and not FDA-approved, so Blue Cross Blue Shield of Michigan typically won't cover it outside clinical trials. Your fastest path: 1) Check if you qualify for ongoing STELLAR trials at ClinicalTrials.gov, 2) Request expanded access through Exelixis if trials aren't suitable, or 3) Discuss approved multi-target TKI alternatives with your oncologist. For coverage appeals, you have 127 days after denial to file external review with Michigan DIFS.

Table of Contents

When Alternatives Make Sense

Since Zanzalintinib (XL092) remains investigational without FDA approval, Blue Cross Blue Shield of Michigan considers it experimental and excludes coverage under standard policies. However, several approved multi-target tyrosine kinase inhibitors (TKIs) share similar mechanisms and may provide therapeutic benefit for your condition.

Consider alternatives when:

  • You don't qualify for clinical trials due to location, eligibility criteria, or trial closure
  • Your oncologist recommends starting treatment immediately rather than waiting for trial enrollment
  • You've exhausted expanded access options through Exelixis
  • Insurance coverage is essential for accessing treatment

Important considerations:

  • Tumor type and stage determine which TKIs are appropriate
  • Prior treatment history affects step therapy requirements
  • Contraindications may limit options (cardiac issues, liver dysfunction)
  • Your oncologist should guide selection based on current NCCN guidelines

Approved Multi-Target TKI Alternatives

For Renal Cell Carcinoma (RCC)

First-line combinations:

  • Lenvatinib + Pembrolizumab: Covered by BCBS Michigan for advanced RCC
  • Cabozantinib + Nivolumab: Targets MET, AXL, and VEGFRs like Zanzalintinib
  • Axitinib + Pembrolizumab: Well-established combination therapy

Monotherapy options:

  • Cabozantinib: Closest mechanism to Zanzalintinib, targeting multiple kinases
  • Sunitinib: Often required as first-line before other TKIs
  • Pazopanib: Alternative first-line option
  • Tivozanib: For patients who've had prior therapy

For Hepatocellular Carcinoma (HCC)

Typical step therapy sequence:

  1. Sorafenib: Usually required first by BCBS Michigan
  2. Lenvatinib: First-line alternative to sorafenib
  3. Cabozantinib: Second-line after sorafenib progression
  4. Regorafenib: After sorafenib failure

Coverage Requirements Table

TKI Indication BCBS Michigan Requirements Monitoring Needed
Cabozantinib RCC, HCC PA required; oncologist prescriber Cardiac, hepatic, renal
Lenvatinib RCC, HCC PA required; may need combination approval Hypertension, proteinuria
Sorafenib HCC Often first-line requirement Hand-foot syndrome, diarrhea
Sunitinib RCC PA required; baseline cardiac assessment Cardiac toxicity, fatigue

Coverage Considerations & Monitoring

Prior Authorization Requirements

BCBS Michigan requires prior authorization for all multi-target TKIs. Your oncologist must submit:

  • Diagnosis with appropriate ICD-10 codes
  • Staging information and performance status
  • Prior treatment history and failures/intolerances
  • Baseline laboratory values (CBC, comprehensive metabolic panel, liver function)
  • Treatment plan and monitoring schedule

Step Therapy Protocols

For HCC: Most BCBS Michigan policies require sorafenib trial before approving other TKIs, unless contraindicated.

For RCC: First-line combinations may be approved without step therapy, but monotherapy TKIs often require prior VEGF-targeted therapy failure.

Laboratory Monitoring Requirements

Multi-target TKIs require regular monitoring:

  • Baseline: Complete blood count, comprehensive metabolic panel, liver enzymes, thyroid function, urinalysis, ECG
  • Ongoing: Every 2-4 weeks initially, then monthly once stable
  • Renal function: Critical for dose adjustments
  • Hepatic function: May require dose reduction or discontinuation
Clinician Corner: When submitting PA requests, emphasize specific molecular targets shared between Zanzalintinib and approved alternatives. Include NCCN guideline citations and document any contraindications to step therapy requirements.

Exception Strategy for Investigational Drugs

While BCBS Michigan typically excludes investigational drugs, exceptions may be possible in rare circumstances. Your strongest case includes:

Medical Necessity Documentation

  • Life-threatening condition with no FDA-approved alternatives
  • Failure or contraindication to all approved therapies
  • Strong clinical rationale from treating oncologist
  • Published evidence supporting off-label use (if applicable)

Required Documentation

  1. Physician attestation detailing medical necessity
  2. Complete treatment history with dates, doses, and outcomes
  3. Laboratory/imaging showing disease progression
  4. Literature review supporting investigational use
  5. Treatment plan with monitoring protocols

Counterforce Health helps patients and providers build comprehensive appeals by analyzing denial letters, identifying specific policy gaps, and crafting evidence-based rebuttals that address payer-specific criteria.

Clinical Trial & Expanded Access Options

Current STELLAR Program Trials

Exelixis is conducting multiple Phase 2/3 trials for Zanzalintinib:

  • STELLAR-304: Advanced non-clear cell RCC
  • STELLAR-303: Metastatic colorectal cancer
  • Additional studies in leiomyosarcoma, prostate cancer, and HCC

Search "Zanzalintinib" or "XL092" at ClinicalTrials.gov for current enrollment status and eligibility criteria.

Expanded Access Program

Exelixis offers expanded access for Zanzalintinib in certain circumstances. Contact:

  • Exelixis Medical Information: [email protected] or 1-855-292-3935
  • Requirements: Serious/life-threatening condition, no trial eligibility, no comparable alternatives

Patient Assistance for Approved Drugs

While Zanzalintinib isn't covered, Exelixis Access Services (EASE) provides support for approved drugs like cabozantinib:

  • Co-pay assistance for commercially insured patients
  • Patient assistance program for uninsured/underinsured
  • 30-day free trial program
  • Contact: 1-844-900-EASE (1-844-900-3273)

Michigan Appeals Process

Internal Appeal (Required First Step)

  1. Submit to BCBS Michigan within their specified timeframe (typically 180 days)
  2. Include all documentation supporting medical necessity
  3. Request peer-to-peer review if available
  4. Wait for final determination before proceeding to external review

External Review Through Michigan DIFS

After internal appeal denial, you have 127 days to file external review:

Standard Process:

Expedited Process (72 hours):

  • Requires physician letter stating delay would harm patient
  • For urgent/life-threatening situations
  • Same documentation requirements

Required for Investigational Drugs:

  • Treating provider must complete DIFS certification form (FIS 2326)
  • Additional evidence of FDA approval status and medical necessity
From our advocates: We've seen success when families work closely with their oncologist to document every approved therapy tried and failed, along with specific contraindications. One case involved a patient who couldn't tolerate standard TKIs due to cardiac issues—the detailed cardiology consultation and alternative mechanism rationale helped secure coverage for a different multi-target approach.

Re-Trying for Zanzalintinib Later

Document Everything During Alternative Treatment

  • Response rates and progression-free survival data
  • Toxicities and dose modifications required
  • Quality of life impacts and functional status
  • Resistance patterns if molecular testing available

Reasons to Re-Request Zanzalintinib

  • FDA approval for your specific indication
  • New clinical trial data supporting use
  • Failure of all approved alternatives
  • Changes in BCBS Michigan coverage policies

Building a Stronger Case

  1. Comprehensive treatment timeline with objective response data
  2. Molecular profiling showing targets relevant to Zanzalintinib
  3. Updated literature supporting use in your tumor type
  4. Quality of life documentation showing need for alternative approach

When FDA approval occurs, Counterforce Health can help transition your case by updating medical necessity arguments with new labeling information and adjusting appeals to reflect changed coverage criteria.

FAQ

How long does BCBS Michigan prior authorization take? Standard PA decisions are typically made within 14 business days. Expedited requests (for urgent situations) are decided within 72 hours.

What if Zanzalintinib becomes FDA-approved while I'm on an alternative? You can request a new PA for Zanzalintinib based on FDA approval. Document your current therapy's effectiveness and any limitations to support the switch.

Can I get coverage if I live near the Michigan border but have BCBS from another state? Coverage policies vary by state. Check your specific Blue Cross plan's investigational drug policy and appeals process in your state.

Does step therapy apply if I failed therapies outside Michigan? Yes, prior treatment history from other states counts toward step therapy requirements. Ensure your Michigan oncologist has complete records.

What counts as medical necessity for investigational drugs? Generally requires: serious/life-threatening condition, failure of approved alternatives, reasonable expectation of benefit, and acceptable risk-benefit ratio based on available evidence.

How much do approved TKI alternatives cost? Costs vary by specific drug and insurance coverage. Most require prior authorization but are covered on specialty tiers. Manufacturer assistance programs can reduce out-of-pocket costs significantly.

Can I appeal if my doctor isn't an oncologist? BCBS Michigan typically requires specialty prescribers for cancer drugs. If your primary care doctor is managing treatment, consider getting an oncology consultation to support your case.

What happens if external review denies coverage? External review decisions are binding in Michigan. However, you may have options to reapply with new evidence or pursue alternative funding through patient assistance programs.

Sources & Further Reading

Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult with your healthcare provider about treatment decisions. Insurance coverage policies change frequently—verify current requirements with your specific plan. For personalized help navigating coverage appeals and building evidence-based cases, consider consulting with Counterforce Health, which specializes in turning insurance denials into successful approvals through targeted, policy-specific appeals.

Powered by Counterforce Health—AI that turns drug denials into evidence-based appeals patients and clinicians can submit today.