Nivolumab + Ipilimumab
Treatment of unresectable Stage III or IV malignant melanoma in patients who experience melanoma recurrence while receiving or within 6 months of completing adjuvant anti-PD-1 inhibitor monotherapy.
Decisions on record
- Meeting Sep 2025 Recommended Unresectable advanced and metastatic cancer (broad multi-indication listing) no PSD
- Meeting Jul 2025 Not recommended Advanced (unresectable) hepatocellular carcinoma Stage A, B or C
- Meeting Jul 2025 Not recommended Unresectable or metastatic MSI-H/dMMR colorectal cancer
- Meeting Jul 2025 Deferred Unresectable advanced and metastatic cancer (broad listing proposal)
- Meeting Mar 2021 Recommended Malignant pleural mesothelioma
- Meeting Nov 2020 Recommended Non-small cell lung cancer (NSCLC)
- Meeting Nov 2019 Recommended Melanoma
Access path
- Nov 2015Not recommended
immature/absent overall survival data (OS not reported for CA209-067, no statistically significant OS benefit in…
- Mar 2017Not recommended
Modest improvement in PFS but substantial increase in adverse events; uncertain net clinical benefit; ICER exceeds…
- Jul 2018Not recommended
Comparator changed: Sequential PD-1 inhibitor monotherapy followed by ipilimumab…
- ↻ resubmittedNov 2022Recommended · restricted
Comparator changed: sunitinib → Ipilimumab (IPI) monotherapy
- PBS listing · Restricted
From the public summary
The PBAC did not recommend nivolumab plus ipilimumab for the first line treatment of microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (mCRC). The PBAC considered that the clinical evidence, which was based on indirect treatment comparisons, was supportive of superior effectiveness, based on progression free survival (PFS), however the magnitude of benefit was uncertain.PSD · Jul 2025
The PBAC considered the primary reason for this outcome was due to the economic evaluation.PSD · Jul 2025
The ESC noted that based on subgroup analyses conducted for patients with centrally confirmed MSI-H/dMMR, PFS was less favourable for nivolumab plus ipilimumab for some subgroups (Figure 3), including for the subgroup of patients with Lynch syndrome24. The ESC considered that it was possible that patients with Lynch syndrome respond more favourably to single agent immunotherapy.PSD · Jul 2025
24 André T et al. Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial. Lancet. 2025 Feb 1;405(10476):383-395. 21 OFFICIALPSD · Jul 2025
The submission described nivolumab plus ipilimumab as superior in terms of effectiveness compared with pembrolizumab. The ESC considered that this claim was adequately supported for PFS, however agreed with the evaluation that the magnitude of the benefit remained uncertain due to limitations associated with the indirect comparisons presented in the submission, including:PSD · Jul 2025
• transitivity issues related to differences in baseline characteristics between CM-8HW 1L and KN-177. Furthermore, there were several potentially important prognostic factors that could not be compared between the trials;PSD · Jul 2025
The PBAC acknowledged input from health care professionals discussing the current treatment of MSI-H or dMMR metastatic or unresectable CRC with single agent pembrolizumab, however noted that patients continue to experience high rates of disease recurrence within 2 years and a poor response to therapy, and discussed the importance of additional treatment options.PSD · Jul 2025
The MOGA also expressed its strong support for the nivolumab plus ipilimumab submission, categorising it as one of the therapies of “Highest Priority” on the basis of the CM-8HW trial. The PBAC noted that the MOGA presented a European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) for nivolumab in combination with ipilimumab, which was limited to 4 (out of a maximum of 5, where 5 and 4 represent the grades with substantial …PSD · Jul 2025
Cost-effectiveness
No economic analysis was provided; the submission relied on CheckMate 067 as a basis for the proposed price in lieu of an economic analysis.
The PSCR accepted this error (& other modifications) to result in an ICER of more than $200,000/QALY gained. PSD · 2017
Decision context
PopulationAdults with unresectable Stage III or IV malignant melanoma who have experienced disease recurrence while receiving adjuvant PD-1 inhibitor monotherapy or within 6 months of completing adjuvant PD-1 inhibitor treatment, with ECOG performance status 0 or 1.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2022 | Recommended · restricted | Ipilimumab (IPI) monotherapy | — | Single-arm · OS |
| Jul 2018 | Not recommended | sunitinib | — | RCT · OS |
| Mar 2017 | Not recommended | Sequential PD-1 inhibitor monotherapy followed by ipilimumab monotherapy upon disease progression | $200k | RCT · PFS |
| Nov 2015 | Not recommended | pembrolizumab monotherapy (primary comparator per PBAC determination); ipilimumab monotherapy and nivolumab monotherapy | — | RCT · PFS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| CheckMate 067 | Ph 3 | 945 | Progression Free Survival (PFS) | completed |
Consumer voice
Health professionals provided input claiming that melanoma patients whose disease progresses on adjuvant therapy experience better clinical outcomes with combination therapy (NIVO + IPI) compared to IPI monotherapy, despite higher adverse event rates.
The input received from health professionals claimed that patients whose melanoma progresses on adjuvant therapy have better clinical outcomes on combination therapy (NIVO + IPI) than on IPI monotherapy, despite the increased incidence of adverse events. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to recurrent unresectable Stage III/IV melanoma after adjuvant PD-1 inhibitor failure; TGA label covers all unresectable/metastatic melanoma without treatment history requirement.