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Keytruda (pembrolizumab) · anti-PD-1 · Merck & Co.
This page covers MSI-H/dMMR solid tumors EXCLUDING colorectal (the tumor-agnostic KEYNOTE-158 indication minus CRC, which is the KEYNOTE-177 page), not the 1L NSCLC, melanoma or other Keytruda settings. See all Keytruda indications →
Label 1.8: 'for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-authorized test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.' This landmark tumour-agnostic indication is NO LONGER accelerated - clinical benefit was verified on 2023-03-28 and it is now a traditional approval. Two scope points: it is second-line-plus only (requires progression on prior treatment AND no satisfactory alternative), and it has no lower age bound on the IV label, unlike Qlex which caps at 12 years and older. Do not confuse with the TMB-H indication (1.18), which remains the single accelerated approval left on this label.
All markets
2026 net revenue · modelled non-CRC MSI-H slice
$816M
CONCLUDED · 2026 modelled net revenue - indication slice, all markets; Merck & Co. reports no indication revenue. Modelled net revenue · sourced funnel
No model change since the 20 Sep 2026 snapshot.
The 15-second read
This is the line whose strategic value obviously exceeds its revenue: KEYNOTE-158 produced the first-ever tumor-agnostic FDA approval (May 2017) and reframed oncology around biomarkers rather than organ of origin, but the non-colorectal MSI-H slice models out as a flat ~$0.8B plateau, $822M at its 2024 peak, barely moving for a decade, then eroding to $339M by 2034 on the ~2028 US LOE. The flatness is the tell: this is a fragmented tail of rare histologies (endometrial-dominant in the West, gastric-heavy in East Asia) reached through a blended MSI-H prevalence of roughly 8% in the West and 4-4.5% in East Asia, and the binding constraint is testing completeness, not competition. Dostarlimab genuinely contests dMMR endometrial, the largest sub-pool, and Merck's own 1L dMMR-endometrial chemo-IO pulls patients out of this later-line setting from above. The honest read: a landmark that pays modestly and has already stopped growing.
Threats land:Tumor-specific 1L IO approvals in dMMR endometrial and gastric absorb patients before they reach this previously-treated setting, and dostarlimab consolidates the endometrial sub-pool, shrinking the line ahead of biosimilars rather than because of them.
Modelled path:The plateau holds through 2027 on incremental testing gains offsetting sub-pool leakage, then pembrolizumab biosimilars from ~2028 US / ~2029 EU take the curve down to $339M by 2034.
Levers land:Universal MSI/MMR testing becomes routine in endometrial and gastric cancer, converting the model's largest funnel leak into identified patients and lifting the plateau above ~$0.8B even as the biomarker pool itself is unchanged.
The MSI/MMR tested-and-identified fraction is an Ormeval scoping estimate and the model's most exposed number, testing is acknowledged as incomplete outside major centres, so the addressable pool is defined by diagnostic practice rather than by disease biology, and no reliable public testing-rate data exists for the rarer histologies.
At a glance
Mechanism anti-PD-1
Clinical
Commercial
Development to approval
These are regulatory approval dates (FDA/EMA/NMPA/PMDA), not commercial launch; launch follows after pricing & reimbursement (see the access-lag column in the HTA table). All four regulators have approved this indication. Cross-checked against Merck & Co. disclosures and regulator databases.
KEYNOTE-158 delivered the first-ever tumor-agnostic, biomarker-defined drug approval (May 2017), a regulatory and scientific milestone that reframed oncology around molecular markers rather than organ of origin, and a template Merck and others have since reused (TMB-high, NTRK, RET). At a ~$0.8B modelled peak the revenue is modest, but the strategic value, pioneering biomarker-agnostic development and entrenching pembrolizumab as the reference checkpoint inhibitor across rare MSI-H tumours, far exceeds its slice. Exposed to the ~2028 biologic LOE like the rest of the franchise.
MSI-H/dMMR is a tumor-agnostic biomarker found across many cancers (endometrial ~25-30%, gastric ~15-20%, small-bowel, biliary, ovarian, prostate and others). KEYNOTE-158 (ORR ~30.8% non-CRC) supported the landmark 2017 tumor-agnostic FDA approval, the first ever based on a biomarker rather than tumour site. This page sizes the NON-colorectal MSI-H pool (colorectal MSI-H is the separate KEYNOTE-177 slice). A modest (~$0.8B) but strategically pioneering slice; dostarlimab (Jemperli) is the principal competitor in dMMR endometrial.
Microsatellite instability-high (MSI-H) / mismatch-repair-deficient (dMMR) tumours carry thousands of frameshift neoantigens, making them exquisitely sensitive to checkpoint blockade regardless of where they arise. The biomarker is most common in endometrial (~25-30%), gastric (~15-20%), small-intestine, biliary, ovarian, and a long tail of rarer cancers; it also defines Lynch-syndrome-associated tumours. Across the 8 modelled markets this NON-colorectal MSI-H/dMMR pool, patients with advanced, previously-treated disease and no satisfactory alternative, totals ~25,000-30,000 patients/year, the pool this model sizes. (Colorectal MSI-H is carved out to the KEYNOTE-177 model.)
KEYNOTE-158 underpinned the first tumor-agnostic FDA approval, pembrolizumab for any previously-treated MSI-H/dMMR solid tumor regardless of site of origin, validating MSI-H/dMMR as a predictive biomarker across histologies. The biomarker-defined cohort (endometrial, gastric, small-intestine, ovarian, biliary and rarer tumours) showed durable responses (ORR ~30-50% across types), establishing pembrolizumab as standard for this molecularly-selected, high-unmet-need population.
Eligibility is biomarker-defined (MSI-H by PCR or dMMR by IHC), not site-defined, testing completeness is the key funnel leak, strongest in endometrial/gastric (often reflex-tested) and weakest in rarer tumours and lower-resource settings. Colorectal MSI-H is carved out to the KEYNOTE-177 model.
Multicohort, single-arm Phase 2 basket trial; MSI-H/dMMR advanced solid tumors of any histology, previously treated, no satisfactory alternative; pembrolizumab 200 mg q3w up to 35 cycles. The non-colorectal MSI-H cohort (endometrial, gastric, small-intestine, ovarian, biliary, and others) supported the tumor-agnostic label; CRC was studied separately.
Load-bearing 4/5 sourced. ASSUMED uptake is yours to change.
This indication only, not Keytruda's total revenue
Previously-treated unresectable/metastatic MSI-H or mismatch-repair-deficient (dMMR) solid tumors of ANY histology EXCLUDING colorectal, pembrolizumab monotherapy (KEYNOTE-158), the first tumor-agnostic, biomarker-defined indication. Colorectal MSI-H is modelled separately (KEYNOTE-177) to avoid double-count.
Reported actuals are always drawn and need no chip: a cited reported figure is a fact, not a claim. Everything forward of them is one of the 4 kinds above.
$816M
8 modelled markets (US, EU5, JP, CN) · modelled net revenue · 2026 (forecast)
Peak $822M · launch 2017 → 2034
modeled history (left of today)·click any year to decompose its funnel below.
Measured band: none - no measured band: n<8
Bull / bear elsewhere in the product are a sensitivity (fixed multipliers), not this band.
Pre-2026 figures are MODELLED and calibrated to Merck's reported Keytruda franchise (FY2025 ≈ $31.7B): the non-CRC tumor-agnostic MSI-H slice is a modest ~$0.8B line, pioneering but small, that rises from the 2017 first-ever agnostic approval to a ~$0.8B plateau, then erodes from ~2028 into the biosimilar cliff. The 'today' marker splits modelled history from forecast.
No reported anchor exists at this grain: companies publish this asset as one product line and never split it by indication × country, so every year above is modelled, including the years already past. The claims below are scored against reported actuals wherever a program has them.
A forecast year closes when an actual is reported for it. A miss is the distance from that actual, signed as the claim fell: under it, or over it.
| Claim | Closed years | Worst miss | Worst miss % |
|---|---|---|---|
| Ormeval modelMODELLED · Ormeval · live | - | no closed year yet | - |
A superseded team version keeps its own row: what it was off by is still a fact about that version. A row with no closed year is not a good score.
What it shows. A modelled base-case net-revenue curve for this indication, year by year, split at 'today' into modelled history and forecast, with the branded curve shown against its in-class rivals.
What to look for. The peak year and how steep the decline is after loss of exclusivity, and where a rival's curve crosses yours, that crossing is the share the model has you losing.
Common misread. Reading the pre-'today' portion as reported actuals (it's modelled), or treating the base case as a company target. It is one deterministic Ormeval-modelled scenario anchored to cited actuals, not guidance and not analyst consensus.
Key model assumptions · The headline rests on the blended MSI-H/dMMR prevalence assumption (~8% West, ~4-4.5% East Asia) applied across a long tail of carrier tumours, and on the testing-and-treated fraction; both are estimates layered on top of one another, so the pool size compounds two soft inputs.
The decline is defended, not certain
The decline is dated and defensible, US composition-of-matter expiry ~2028, EU ~2029, but in a fragmented rare-tumour setting, biosimilar penetration may be slower than in high-volume indications, and SC Qlex (Sep 2025) is a real if unquantified volume defense, so the 2030-2034 tail could sit above the modelled level.
What would change our mind
If the 1L dMMR-endometrial chemo-IO regimen (NRG-GY018) becomes standard-of-care fast enough that endometrial patients rarely reach a previously-treated tumor-agnostic line, the base case is wrong before 2028, the plateau would break downward on cannibalization, not on the LOE.
A scenario is your own assumptions layered on Ormeval’s cited baseline. We never change the baseline; save as many named scenarios as you like and click one to load it back later.
| Driver · 2026 | US | FR | DE | IT | ES | UK | JP | CN | Total | Source |
|---|---|---|---|---|---|---|---|---|---|---|
| MSI-H-bearing solid-tumor incidence (non-CRC carriers) (2026) | 168k | 39k | 53k | 37k | 28k | 41k | 179k | 1.17M | 1.72M | GLOBOCAN 2022 |
Combined incidence of the principal non-CRC tumour types that carry MSI-H/dMMR (endometrial, gastric, small-bowel, ovarian, biliary, other); +1%/yr. Shown for 2026: 2024 basis +1%/yr → ×1.020. The incidence base is the pooled population of the main non-colorectal tumour types in which MSI-H/dMMR occurs (endometrial dominates, then gastric, ovarian, biliary, small-bowel and a rare-tumour tail). The MSI-H FRACTION is applied in the rates below. Per-market figures are pooled GLOBOCAN 2022 incidence of these carrier tumours; gastric-heavy markets (Japan, China) carry larger bases but lower endometrial MSI-H share. | ||||||||||
| × MSI-H/dMMR fractionest | 9% | 9% | 8% | 8% | 9% | 9% | 5% | 4% | share, not summed | Bonneville · Cortes-Ciriano |
Fraction of the carrier-tumour pool that is MSI-H/dMMR (endometrial ~25-30%, gastric ~15-20%, others lower), pooled to a blended rate. Pooled MSI-H/dMMR prevalence across the carrier mix. Endometrial-heavy Western pools blend to ~7-9%; gastric-heavy East-Asian pools (where gastric dominates and endometrial is a smaller share, but gastric MSI-H is meaningful) blend lower (~4-5%) on a much larger base. A deliberately conservative blended fraction reflecting the fragmented carrier mix. | ||||||||||
| × Advanced, tested, treated (non-CRC)est | 46% | 44% | 44% | 42% | 42% | 44% | 42% | 20% | share, not summed | testing audits |
Of MSI-H carriers, those with advanced previously-treated disease, MSI/MMR-tested, fit for and receiving checkpoint therapy. Branded pembrolizumab UPTAKE is the share row below. Combines (a) the advanced/recurrent fraction eligible for systemic IO, (b) MSI/MMR testing completeness (incomplete outside major centres, the key leak), and (c) fitness for and receipt of checkpoint therapy. Higher where reflex testing is routine and access broad (~0.42-0.46 West, Japan); markedly lower in China (~0.20, testing and access tier-concentrated). Excludes pembrolizumab UPTAKE (the share layer below). | ||||||||||
| = Addressable non-CRC MSI-H/dMMR pool | 6.6k | 1.4k | 1.9k | 1.2k | 983 | 1.5k | 3.4k | 9.4k | 26k | computed |
Carrier-tumour incidence × MSI-H fraction × advanced/tested/treated, non-CRC MSI-H patients reachable for checkpoint therapy this year. The non-CRC MSI-H pool is stable-to-rising, expanding universal MSI/MMR testing (especially in endometrial and gastric) identifies more eligible patients over time, roughly offset by 1L dMMR-endometrial chemo-IO absorbing some patients before this later-line setting. Modelled flat; testing-driven growth is captured in the tested/treated gate. | ||||||||||
| × Keytruda uptake (branded) | 38% | 36% | 38% | 36% | 36% | 36% | 44% | 24% | share, not summed | ASSUMED |
Per-market branded uptake of the addressable pool this year (launch ramp net of competitors & biosimilars). See the competitive curve below; pick a market for its access basis. | ||||||||||
| = Treated with Keytruda | 2.5k | 524 | 714 | 443 | 353 | 552 | 1.5k | 2.3k | 8.9k | computed · assumed input |
Addressable pool × branded uptake. | ||||||||||
| × Net price / patient (2026) | $173K | $91K | $96K | $86K | $77K | $85K | $67K | $24K | per patient, not summed | ASP · HTA · NHI |
Until-progression IO: per-patient revenue is the annual net cost while on-drug. US ASP ≈ $11.8k/200mg q3w (~$205k/yr list) net of ~10-15% GTN → ~$180k/yr. EU nets ~$80-100k. Japan ~$70k. China ~$25k. −2%/yr forward; held flat before 2024. SHOWN FOR 2026: the per-market figures in "Net pricing: assumptions & basis" below are the 2024 basis; this row applies -2%/yr from 2024 (×0.9604), so it is the same source value at a later date, not a second price. | ||||||||||
| = Net revenue / yrOutput | $433M | $47.8M | $68.6M | $38.3M | $27.1M | $46.6M | $99.4M | $54.7M | $816M | computed · assumed input |
Treated patients × realized net price. | ||||||||||
Regional revenue mix · 2026 modelled
Model estimate, sourced from the funnel table above
No reported competitor-share series exists for this setting, so every trajectory below is modelled from approval timing, label breadth and the funnel, not reported data.
In-class share, MSI-H/dMMR tumor-agnostic immunotherapy (non-CRC): 8 modelled markets (US, EU5, JP, CN)
Each agent's share of the addressable non-CRC MSI-H pool. The branded-pembrolizumab line shows the launch ramp from the 2017 tumor-agnostic approval, then the ~2028 LOE erosion; the gap below the top line is patients on dostarlimab, other checkpoint inhibitors, or untested/untreated. The branded pembrolizumab line (IV + SC Qlex) is the only line this model monetizes.
Share of the 26k-patient addressable non-CRC MSI-H/dMMR pool this regimen is modelled to treat, by year
Keytruda is modelled at 34% of this pool in 2026, peaking at 34% in 2026; each point of share is revenue on the chart above.
Scope: 8 modelled markets (US, EU5, JP, CN) · follows the market selector above
Rivals' share, same pool
Other checkpoint inhibitors holds the largest rival share in 2026, 7% of the pool; that is the share Keytruda has to take or hold.
Rivals, rescaled - note the axis maximum (20%), which is smaller than the plot above. Same data, a linear axis of its own, so a low-share entrant is readable rather than a hairline on the baseline.
Launch ramp = approval timing (US agnostic May 2017); dostarlimab (Jemperli, US 2021) takes dMMR-endometrial share; pembrolizumab biosimilars timed to ~2028 US / ~2029 EU LOE. Competitor trajectories are stated assumptions.
Readouts, approvals and LOE events for pembrolizumab and its rivals in this setting. Estimated timing is flagged; confirmed dates cited from Merck & Co. disclosures and regulator databases.
Composition-of-matter expiry (~2028); pembrolizumab biosimilars erode the branded MSI-H line
EU biosimilar entry; SC Qlex conversion mitigates share loss
✓ = reported public fact, cited. Upcoming timing is estimated from company guidance and trial registries, a projection, not a commitment. Approvals = US (FDA) · EU (EMA) · Japan (PMDA) · China (NMPA). ● = pembrolizumab, competitor tag = a same-setting rival.
Residual unmet need: why the field stays alive
Despite the biomarker's strong predictive value, ~50-70% of MSI-H/dMMR non-CRC patients still do not respond durably to pembrolizumab monotherapy, and primary/acquired resistance occurs. MSI-H testing is incomplete outside major centres (a real access leak, especially in rarer tumours and lower-resource markets), and there is no established post-pembrolizumab standard in this molecularly-selected group. These gaps sustain interest in IO combinations and next-generation checkpoint agents for the biomarker-defined population.
The synthesis for this indication, grounded in the cited trial, guideline and access facts above.
Rivals in this setting (MSI-H/dMMR solid tumors (tumor-agnostic, non-CRC))
Swipe to explore →
| Rival / regimen | Developer | Position in this setting | Approved (date, trial, n) | Head start vs this regimen (months) | Source |
|---|---|---|---|---|---|
| Dostarlimab (Jemperli) (Live threat) | GSK | Live threatwhyFDA-approved dMMR endometrial (2021) and 1L dMMR endometrial chemo-IO (RUBY), the direct competitor in the largest MSI-H sub-pool | not in the record | not in the record | GARNET / RUBY |
| Nivolumab ± ipilimumab (Watch) | Bristol Myers Squibb | WatchwhyCompetes in MSI-H niches (notably CRC, modelled separately); smaller non-CRC presence | not in the record | not in the record | CheckMate-142 (MSI-H CRC) / tumour-specific |
| 1L dMMR endometrial chemo-IO (pembro NRG-GY018) (Merck & Co. pipeline) | Merck (intra-franchise) | Merck & Co. pipelinewhyMoves dMMR-endometrial patients to 1L pembrolizumab, partly cannibalizes this later-line slice but stays within the franchise | not in the record | not in the record | NRG-GY018 |
| Domestic Chinese PD-1s (MSI-H/agnostic) (China rival) | Innovent / others | China rivalwhySome domestic PD-1s carry MSI-H/agnostic data, China-only share pressure | not in the record | not in the record | tumour-specific China trials |
| Keytruda Qlex (subcutaneous) (Merck & Co. pipeline) | Merck | Merck & Co. pipelinewhyFDA-approved Sep 2025, intra-brand LOE/convenience defense (monetized within the branded line) | Sep 2025, - | -100 (after) | - |
| Pembrolizumab biosimilars (Watch) | Generic (post-LOE) | WatchwhyUS LOE ~2028; EU ~2029, erosion of the branded MSI-H line | not in the record | not in the record | pembrolizumab composition-of-matter LOE ~2028 (US) |
Not every rival is approved in every region, so a share here is the modelled position in the markets where it competes, not a global one.
Net pricing: assumptions & basis
Pembrolizumab is dosed 200 mg q3w (or 400 mg q6w) IV, or via subcutaneous Qlex (Sep 2025), until progression or 35 cycles (~2-year cap), so per-patient revenue is the annual net cost while on-drug. US ASP ~$11.8k per 200 mg; net prices below are per-market.
Figures below are 2024 net prices, the basis the model is anchored on. The funnel applies -2%/yr from 2024, so the price it consumes for a later year is lower than the figure quoted here. Both come from this one value; the funnel row states the year it is showing.
Pembrolizumab is dosed 200 mg q3w (or 400 mg q6w) IV, or as SC Qlex (FDA Sep 2025), until progression or a 35-cycle (~2-year) cap, so per-patient revenue is the annual net cost while on treatment. US ASP ≈ $11,795/200 mg q3w (~$205k/yr list) ⇒ ~$180k/yr net after ~10-15% GTN. EU nets HTA-negotiated (~$80-100k). Japan NHI ~$70k. China small-reach/access-limited (~$25k). −2%/yr forward; held flat before 2024. ALL net prices are ESTIMATES.
What it shows. The approval-to-reimbursement journey by market: when each payer granted access, on what terms (PD-L1 or comparator restrictions), and the lag between regulatory approval and reimbursed revenue.
What to look for. The access-lag column, approval is not revenue and some markets take a year or more. And the restrictions that narrow the eligible population below the full label.
Common misread. Assuming a US price or approval transfers to other markets. Ex-US payers benchmark against comparators and reference prices, so the net price and the covered population are usually smaller.
Rows ordered by access speed. The approval→reimbursement lag is commercially load-bearing, and it is not one number per drug: a monotherapy indication and a later combination extension file separately with a payer and can reach routine commissioning years apart, even within the same asset’s first-line setting.
| Market | HTA body | Decision | Access lag | PD-L1 | Comparator | Key outcome / MEA note |
|---|---|---|---|---|---|---|
| US | FDA | 23 May 2017 (tumor-agnostic) | reference | None (MSI-H/dMMR gate) | - | Medicare Part B (J9271); first tumor-agnostic approval; biomarker-gated coverage |
| Germany | G-BA / IQWiG | 2018-2019 | ~0.6 yr | MSI-H/dMMR | BSC | Tumour-specific reimbursement; AMNOG; densest EU access |
| UK | NICE | 2019-2021 | ~1.5 yr | MSI-H/dMMR | BSC | Tumour-specific recommendations (e.g. endometrial); confidential PAS |
| France | HAS | 2018-2020 | ~0.8 yr | MSI-H/dMMR | BSC | Early access then reimbursement; tumour-specific |
| Italy | AIFA | 2019-2021 | ~1.5 yr | MSI-H/dMMR | BSC | Class H; managed entry; +regional formulary lag |
| Spain | SEFH / MoH | 2019-2021 | ~2 yr | MSI-H/dMMR | BSC | Financed; +17-region formulary lag |
| Japan | PMDA / NHI | Dec 2018 (tumor-agnostic) | ~0.5 yr | MSI-H/dMMR | BSC | PMDA approved a tumor-agnostic MSI-H indication; NHI-listed; biennial price cuts |
| China | NMPA | 2022 | ~3 yr | MSI-H/dMMR | BSC | Later tumor-agnostic MSI-H approval; testing/access-limited; modest uptake |
How much each assumption could move the forecast, one at a time, over the same cited baseline.
This is a sensitivity illustration, not a probability: it shows how far each assumption could move the forecast, never how likely it is.
Set a target and solve for one lever, what it would have to reach, benchmarked against real comparable launches.
One lever at a time: the other assumptions stay at baseline, so the trade-off stays visible.
A model that shows where its own risk is, not a number to trust. Never investment advice.
Cite this forecast as recorded on Q2 2026 → A permanent record of these figures that does not change when the model does.
Every reported figure here traces to a public source below; the model's own assumptions are labelled where they appear.
Reported figures are public facts from company filings; the forward peak is Ormeval's own modelled estimate, not company guidance and not analyst consensus. Approval and readout dates are cross-checked against public regulator and company disclosures. Not investment advice.