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Keytruda (pembrolizumab) · anti-PD-1 + fluoropyrimidine/platinum · Merck & Co.
This page covers HER2-NEGATIVE 1L gastric/GEJ adenocarcinoma only. The HER2-POSITIVE 1L indication built on KEYNOTE-811 is a separate approval with its own page, and the two partition the same incidence denominator (~18% positive, ~82% negative) rather than overlapping. Esophageal squamous disease (KEYNOTE-590) and biliary tract cancer (KEYNOTE-966) are separate rows again. See all Keytruda indications →
Missing row, now added. Distinct from the HER2-POSITIVE gastric/GEJ indication built on KEYNOTE-811 elsewhere on this asset - that row is a separate approval, not this one. SCOPE HAS DRIFTED, same class as KEYNOTE-811 and KEYNOTE-590 on this asset: the FDA approval notice for 2023-11-16 states the indication as 'first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma' with NO PD-L1 threshold in the approved indication itself (the notice reports CPS>=1/CPS>=10 only as an efficacy subgroup finding). The CURRENT label section 1.10, read 2026-09-16, restricts the combination to 'whose tumors express PD-L1 (CPS >=1)' - narrower than the all-comers 2023 approval, and matching the EU scope from the outset. The exact US supplement that added the CPS>=1 gate is not established here; do not infer a date for it.
All markets
2026 net revenue · modelled HER2-negative gastric slice
$321M
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 larger gastric pool and the weaker commercial position. HER2-negative disease is roughly 82% of advanced gastric and GEJ adenocarcinoma against 18% HER2-positive, so the funnel is four times wider. But pembrolizumab arrived third: nivolumab plus chemotherapy (CheckMate-649) has held this line since 2021, tislelizumab holds the PD-L1-high slice in China, and zolbetuximab removes the CLDN18.2-positive third of the pool. Modelled peak is $511M in 2027 on a third-entrant share, and the 2028 biologic cliff takes it to $214M by 2034.
Threats land:Nivolumab's incumbency proves stickier than modelled, zolbetuximab takes more of the CLDN18.2-positive third than the ~38% screening prevalence implies, and branded pembrolizumab never clears a fifth of the Western pool before biosimilars arrive.
Modelled path:Pembrolizumab settles as the second checkpoint inhibitor of three in the PD-L1 CPS>=1 pool, peaks near $511M in 2027, and erodes on US biosimilar entry from ~2028 and EU from ~2029 to roughly $214M by 2034.
Levers land:The CPS>=1 label gate tightens prescribing toward the agent with the cleanest CPS>=1 evidence, subcutaneous Qlex conversion holds branded volume through the IV biosimilar wave, and the plateau extends a year past the modelled peak.
Branded penetration of the CPS>=1 pool, and nothing else comes close. The denominator chain is the same one the HER2-positive page uses and is as well grounded as gastric epidemiology gets. What is genuinely uncertain is how much of an already-served line a third entrant takes: nivolumab has been the 1L HER2-negative standard since 2021, prescriber inertia in a chemo-backbone regimen is high, and the modelled ~30% US mature penetration is an assumption benchmarked to that incumbency rather than a measured share.
At a glance
Mechanism anti-PD-1 + fluoropyrimidine/platinum
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-859 completes the Keytruda upper-GI set: with KEYNOTE-811 (HER2-positive gastric), KEYNOTE-590 (esophageal) and KEYNOTE-966 (biliary tract), pembrolizumab now carries a label in every major 1L upper-GI adenocarcinoma setting. Commercially it is the largest of those pools and the least defensible position in it. The value of the indication is breadth of label rather than share of line, and it arrives with about four years of exclusivity left.
HER2-negative disease is roughly 82% of advanced gastric and GEJ adenocarcinoma, against ~18% HER2-positive. KEYNOTE-859 established pembrolizumab plus chemotherapy here (OS HR 0.78); the FDA approved it on 2023-11-16 and the European Commission followed on 2023-12-18. The label now gates the combination on PD-L1 CPS>=1. Nivolumab plus chemotherapy has been the standard since 2021, so this is modelled as a third-entrant share (~$511M peak), not a standard-of-care one.
Advanced gastric and GEJ adenocarcinoma first bifurcates on HER2. The HER2-positive minority goes to a trastuzumab-plus-chemotherapy backbone. The HER2-negative majority, roughly 82%, is where checkpoint inhibition plus chemotherapy became standard, first with nivolumab on CheckMate-649 from 2021 and then with pembrolizumab on KEYNOTE-859 from late 2023. Both are now gated on PD-L1 expression. The pool is further fragmented by zolbetuximab, which takes the CLDN18.2-positive slice, about a third of HER2-negative patients in the pivotal screening populations. The addressable funnel here is incidence, times the advanced fraction, times HER2-negative, times CPS>=1 tested and treated.
KEYNOTE-859 tested pembrolizumab added to fluoropyrimidine and platinum chemotherapy against chemotherapy alone in first-line HER2-negative advanced gastric and gastroesophageal junction adenocarcinoma, and met its overall-survival endpoint. It is the trial that put pembrolizumab into a line nivolumab had already held for two years.
Eligibility is HER2-negative status plus PD-L1 CPS>=1. Guideline bodies list pembrolizumab and nivolumab side by side without preference, which is the commercial problem this page models.
Randomized, double-blind, placebo-controlled Phase 3 (NCT03675737, completed): pembrolizumab plus fluoropyrimidine- and platinum-containing chemotherapy versus placebo plus the same chemotherapy, in previously untreated locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma. Primary endpoint overall survival.
Load-bearing 5/6 sourced. ASSUMED uptake is yours to change.
This indication only, not Keytruda's total revenue
Pembrolizumab added to fluoropyrimidine- and platinum-containing chemotherapy in first-line locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma (KEYNOTE-859). The current US label restricts the combination to tumours expressing PD-L1 with CPS>=1, matching the EU scope. Only the pembrolizumab component is monetized here.
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.
$321M
8 modelled markets (US, EU5, JP, CN) · modelled net revenue · 2026 (forecast)
Peak $348M · launch 2023 → 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): this slice rises from the Nov 2023 launch to a ~$511M peak in 2027, about 1.6% of the franchise, then erodes from ~2028 into the biosimilar cliff. It is the wider of the two gastric pools and the weaker position in it. 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 · Two soft inputs carry the headline. First, the third-entrant share above, benchmarked to the CheckMate-649 incumbency rather than to any disclosed split. Second, the PD-L1 CPS>=1 gate at ~65%, taken from the screening range this repository already records for KEYNOTE-859 and CheckMate-649 (~60-80%) at the conservative end. The price layer is the firmest element: it is the same pembrolizumab net price, at the same dose, that the HER2-positive page uses.
The decline is defended, not certain
The fall from $511M in 2027 to $214M in 2034 is the franchise biologic cliff (~2028 US, ~2029 EU), not anything specific to gastric cancer. It bites harder here than in a sole-option setting: a prescriber already choosing between three interchangeable PD-1 agents has no reason to prefer the branded one once a biosimilar of any of them is cheaper.
What would change our mind
The base case is wrong if zolbetuximab plus chemotherapy displaces checkpoint blockade rather than partitioning the pool. If CLDN18.2-directed therapy becomes the preferred 1L choice for that third of patients rather than an addition to it, the pool this page sizes shrinks by more than the modelled ~12%. The observable trigger is a 1L guideline change, not a trial readout.
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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Gastric/GEJ cancer incidence | 32k | 6.6k | 15k | 15k | 6.9k | 6.8k | 126k | 359k | 566k | GLOBOCAN 2022 |
New stomach cancer cases per year, including cardia/GEJ. Held flat (Western decline offset by ageing and the East-Asian burden). The same country-specific GLOBOCAN 2022 stomach-cancer incidence this repository uses for the HER2-POSITIVE gastric page, deliberately identical so the two pages partition one denominator instead of sizing two. China and Japan together hold the great majority of the 8-market total. | ||||||||||
| × Locally advanced unresectable / metastaticest | 45% | 45% | 45% | 45% | 45% | 45% | 30% | 45% | share, not summed | SEER · screening |
The 1L-eligible advanced fraction. Lower in Japan, where endoscopic screening shifts diagnosis earlier. Identical to the advanced fraction the HER2-positive gastric page carries, for the same reason the incidence row is identical: the two pages split one pool. ~45% West and China, ~30% Japan. | ||||||||||
| × HER2-negativeest | 82% | 82% | 82% | 82% | 82% | 82% | 82% | 82% | share, not summed | ToGA · meta (complement) |
The complement of the HER2-positive fraction. HER2-positive disease goes to the trastuzumab backbone and is out of this pool. Taken as 1 minus the ~18% HER2-positive rate this repository already models for the sibling indication. Stating it as a complement rather than as a fresh estimate is what stops the two pages from over-allocating the same incidence. | ||||||||||
| × CPS≥1, tested & treatedest | 55% | 54% | 54% | 52% | 52% | 53% | 55% | 36% | share, not summed | KN-859 / CM-649 (~65%) |
PD-L1 CPS>=1 (the current label gate) AND tested, fit for and receiving a 1L chemo-IO regimen. Branded UPTAKE is the share row below. The ~65% CPS>=1 figure is the conservative end of the ~60-80% screening range this repository already records for these two trials. Multiplied by PD-L1 testing completeness and the fraction fit for a chemo-IO regimen (~85% West and Japan, ~55% China, tier-concentrated) it gives ~0.55 in the developed markets and ~0.36 in China. Branded uptake is NOT in this row. | ||||||||||
| = Addressable 1L HER2-negative CPS>=1 pool | 6.4k | 1.3k | 2.9k | 2.8k | 1.3k | 1.3k | 17k | 48k | 81k | computed |
Incidence × the rates above: advanced HER2-negative CPS>=1 gastric/GEJ patients reachable for a 1L chemo-IO regimen this year. The pool is held flat. Gastric incidence is flat to declining in the West and the rise in PD-L1 testing completeness is already inside the CPS>=1 reach row, so growing the pool as well would count the same improvement twice. | ||||||||||
| × Keytruda uptake (branded) | 14% | 10% | 10% | 6% | 7% | 6% | 6% | 2% | 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 | 866 | 129 | 288 | 174 | 89 | 85 | 1.1k | 821 | 3.5k | computed · assumed input |
Addressable pool × branded uptake. | ||||||||||
| × Net price / patient (2026) | $178K | $86K | $91K | $82K | $77K | $85K | $72K | $27K | per patient, not summed | ASP · HTA · NRDL |
The same pembrolizumab net-price row the HER2-positive gastric page carries, unchanged: same molecule, same dose, same markets, same until-progression regimen. US ASP ≈ $11.8k/200mg q3w (~$205k/yr list) net of ~10-15% GTN gives ~$185k/yr. EU nets ~$80-95k. Japan ~$75k. China NRDL ~$28k. −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 | $154M | $11.2M | $26.3M | $14.2M | $6.8M | $7.2M | $78.9M | $22.1M | $321M | 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, 1L HER2-negative gastric/GEJ (CPS≥1): 8 modelled markets (US, EU5, JP, CN)
Each agent's share of the addressable 1L HER2-negative CPS>=1 pool. Branded pembrolizumab is a third-entrant ramp against the standard nivolumab set in 2021. The gap below the top lines is patients on chemotherapy alone, on zolbetuximab, or untreated. Only branded pembrolizumab (IV plus SC Qlex) is monetized here.
Share of the 81k-patient addressable 1L HER2-negative CPS>=1 pool this regimen is modelled to treat, by year
Keytruda is modelled at 4% of this pool in 2026, peaking at 5% in 2028; 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
Nivolumab (Opdivo) + chemo holds the largest rival share in 2026, 5% of the pool; that is the share Keytruda has to take or hold.
Rivals, rescaled - note the axis maximum (8%), 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 2023-11-16, EU announced 2023-12-18, Japan est. 2024, China not asserted). Nivolumab + chemo (CheckMate-649) is modelled as the incumbent from 2021; tislelizumab (RATIONALE-305) takes China PD-L1-high share; zolbetuximab (SPOTLIGHT/GLOW) removes the CLDN18.2-positive slice; pembrolizumab biosimilars are timed to the ~2028 US and ~2029 EU LOE. Every competitor trajectory is a stated assumption, not a disclosed figure.
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); biosimilars erode a line where three PD-1 agents are already interchangeable
EU biosimilar entry; SC Qlex conversion partly defends branded volume
✓ = 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
Median survival in advanced gastric cancer remains measured in months, and the incremental benefit of adding a checkpoint inhibitor to chemotherapy (OS HR 0.78) is real but modest. CPS-low and CPS-negative patients gained least, which is why the label narrowed, and they have no better option. Biomarker-directed alternatives are only starting to appear: zolbetuximab addresses CLDN18.2-positive disease, leaving the CLDN18.2-negative, PD-L1-low majority with chemotherapy and little else.
The synthesis for this indication, grounded in the cited trial, guideline and access facts above.
Rivals in this setting (1L HER2-negative gastric / GEJ adenocarcinoma)
Swipe to explore →
| Rival / regimen | Developer | Position in this setting | Approved (date, trial, n) | Head start vs this regimen (months) | Source |
|---|---|---|---|---|---|
| Nivolumab (Opdivo) + chemo (Live threat) | Bristol Myers Squibb / Ono | Live threatwhyTHE INCUMBENT of this exact line since 2021, and the analogue the branded share assumption here is benchmarked against. Approved 1L HER2-negative gastric/GEJ in the US, EU and across Asia. | not in the record | not in the record | CheckMate-649, nivolumab + chemo 1L HER2-negative gastric/GEJ, ClinicalTrials.gov NCT02872116 |
| Tislelizumab + chemo (China rival) | BeOne Medicines | China rivalwhyNMPA-approved 1L in PD-L1-high gastric/GEJ (median OS 17.2 vs 12.6 months, p=0.006); NRDL-listed and far cheaper, structural China share pressure. | not in the record | not in the record | RATIONALE-305 |
| Zolbetuximab (Vyloy) + chemo (Pool erosion) | Astellas Pharma | Pool erosionwhyApproved 1L for HER2-negative CLDN18.2-positive disease. Removes roughly a third of HER2-negative patients from this pool rather than competing for them on the same axis. | not in the record | not in the record | SPOTLIGHT / GLOW |
| Trastuzumab + chemo ± pembrolizumab (HER2-positive) (Ex-US rival) | Roche / Merck | Ex-US rivalwhyThe adjacent HER2-POSITIVE line, out of this pool by definition. Listed so the partition between the two gastric pages is explicit. | not in the record | not in the record | ToGA / KEYNOTE-811 |
| Keytruda Qlex (subcutaneous) (Merck & Co. pipeline) | Merck | Merck & Co. pipelinewhyFDA-approved Sep 2025; intra-brand convenience and LOE defence, monetized within the branded line. | Sep 2025, - | -22 (after) | - |
| Pembrolizumab biosimilars (Watch) | Generic (post-LOE) | WatchwhyUS LOE ~2028, EU ~2029. Erosion is sharper here than in a sole-option setting because three PD-1 agents are already interchangeable in this regimen. | not in the record | not in the record | pembrolizumab 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 added to fluoropyrimidine/platinum chemotherapy, dosed 200 mg q3w (or 400 mg q6w) until progression, so per-patient revenue is the annual net cost of the pembrolizumab component alone. The chemotherapy is separate spend. 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.
Per-patient revenue is modelled as the annual net cost of the pembrolizumab component only, at 200 mg q3w (or 400 mg q6w) until progression. US ASP ≈ $11,795 per 200 mg (~$205k/yr list) gives ~$185k/yr net after ~10-15% GTN. EU nets are HTA-negotiated (~$80-95k), Japan NHI ~$75k, China NRDL ~$28k. Forward erosion −2%/yr, held flat before 2024. ALL net prices are ESTIMATES. They are deliberately identical to the HER2-positive gastric page, because a different net price for the same molecule in the same market would be an artefact of curation rather than a fact.
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 | 16 Nov 2023 (BLA125514 SUPPL 143) | reference | CPS >=1 (current label) | Chemotherapy alone | Medicare Part B (J9271); until progression; the highest-price market despite low US gastric incidence |
| EU (EC) | European Commission | 18 Dec 2023 (announced) | ~0.1 yr | CPS >=1 | Chemotherapy alone | EU scope carried the CPS>=1 gate from the outset; national reimbursement follows per market |
| Germany | G-BA / IQWiG | 2024 | ~0.4 yr | CPS >=1 | Chemotherapy alone | AMNOG-rebated; densest EU access |
| France | HAS | 2024 | ~0.6 yr | CPS >=1 | Chemotherapy alone | Reimbursed post-EC; cited by link only, not machine-read |
| Italy | AIFA | 2024-2025 | ~1.5 yr | CPS >=1 | Chemotherapy alone | Class H plus regional formulary lag |
| Spain | SEFH / MoH | 2025 | ~2 yr | CPS >=1 | Chemotherapy alone | Financed; plus 17-region formulary lag |
| UK | NICE | 2024-2025 | ~1 yr | CPS >=1 | Chemotherapy alone | Confidential PAS; cited by link only, not machine-read |
| Japan | PMDA / NHI | 2024 (est.) | ~0.7 yr | PD-L1+ | Chemotherapy / nivolumab + chemo | NHI-listed. Nivolumab is the domestic-partnered incumbent here (Ono), so branded uptake is modelled lowest of the developed markets |
| China | NMPA / NRDL | not asserted | n/a | n/a | Tislelizumab + chemo (RATIONALE-305) | This repository records that Merck's Chinese gastric label position was NOT verified from a primary public source. No date is asserted; China is modelled at a low residual share behind NRDL-listed domestic PD-1s |
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.
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.