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Keytruda (pembrolizumab) · anti-PD-1 · Merck & Co.
This page covers 1L HER2-POSITIVE gastric/GEJ only (KEYNOTE-811, CPS≥1), not the HER2-negative 1L setting (nivolumab, CheckMate-649) or 2L+ T-DXd, which are modelled/handled separately. See all Keytruda indications →
SCOPE CORRECTION. On label, year correct, but the row omits a biomarker gate that now exists. Current label 1.10: 'in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS >=1).' The original 2021-05-05 accelerated approval carried NO PD-L1 requirement - the FDA accelerated-approval registry records it as HER2-positive gastric/GEJ with no biomarker qualifier. The indication was subsequently narrowed to CPS >=1 and converted to traditional approval on 2025-03-19. HER2-positive-but-PD-L1-negative patients are now outside the label, which materially shrinks the addressable population versus the 2021 launch assumption.
All markets
2026 net revenue · modelled gastric slice
$565M
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
1L HER2+ gastric/GEJ is a strategic foothold rather than a revenue line: at a modelled $684M peak in 2028 it is roughly 2% of Merck's ~$31.7B Keytruda franchise, and it is doubly biomarker-gated, HER2-positive (about 18% of advanced gastric) and then PD-L1 CPS≥1 (about 85% of those, after CPS-negative patients showed an OS hazard ratio near 1.41 and were excluded). The clinical position is settled and modest: pembrolizumab adds to the trastuzumab-plus-chemo backbone rather than replacing it, delivering OS HR 0.80 and median 20.0 versus 16.8 months, now on full traditional approval since Mar 2025. The commercial geography is unhelpful, China and Japan carry roughly 85% of gastric incidence but at NRDL and NHI net prices, so revenue concentrates in the West where incidence is lowest. And the peak arrives the same year US exclusivity lapses. The honest read: a well-earned guideline position with almost no runway to monetise it.
Threats land:Cheaper domestic Chinese PD-1 plus trastuzumab regimens take the largest incidence market outright while biosimilar pembrolizumab arrives on schedule from ~2028, so the plateau is shorter and shallower than modelled.
Modelled path:The regimen holds its NCCN Category 1 position in the CPS≥1 pool, peaks at about $684M in 2028, and erodes on US biosimilar entry from ~2028 and EU from ~2029 to roughly $321M by 2034.
Levers land:Keytruda Qlex subcutaneous conversion retains branded volume through the IV biosimilar wave while rising HER2-testing completeness enlarges the identified eligible pool, holding the post-2029 tail above the modelled path.
The advanced/metastatic fraction of gastric cancer, an Ormeval scoping estimate of roughly 40–50% in the West and China but only about 30% in Japan because of screening, which the digest itself flags as the largest cross-market estimate and the primary sensitivity, sitting above the HER2+ and CPS≥1 gates.
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.
1L HER2+ gastric/GEJ extended Keytruda into upper-GI oncology and demonstrated that anti-PD-1 could add survival on top of a targeted-antibody + chemo backbone. At a ~$0.7B modelled peak it is a small but genuine franchise slice, narrow (biomarker-gated to HER2+ AND CPS≥1) and concentrated in markets (China/Japan) where net prices are low, so it is more a strategic foothold in GI cancer than a major revenue line. Its full traditional approval (Mar 2025, on mature OS) cements the position ahead of the ~2028 LOE.
HER2-positive gastric/GEJ adenocarcinoma, ~15-22% of advanced gastric cancer, has been a trastuzumab+chemo (ToGA) setting since 2010. KEYNOTE-811 added pembrolizumab on top, improving OS (HR 0.80; CPS≥1 0.79) and PFS (HR 0.73), now restricted to PD-L1 CPS≥1 (~85%). It is a small, biomarker-gated franchise slice (~$0.7B modelled peak): China and Japan carry the vast majority of gastric incidence but at deeply discounted net prices, so the West drives revenue per patient.
Gastric and gastroesophageal junction adenocarcinoma is a high-incidence cancer in East Asia (China and Japan together hold ~85% of global cases) but much rarer in the West. The advanced/metastatic 1L-eligible fraction is ~40-50% in the West/China but lower in Japan (~25-35%, where endoscopic screening shifts diagnosis earlier). Treatment first bifurcates on HER2: HER2-positive disease (~15-22%, ToGA screening 22.1%) goes to a trastuzumab + chemotherapy backbone, onto which pembrolizumab is added if PD-L1 CPS≥1 (~85%). HER2-negative disease (the majority) goes to a different IO regimen (nivolumab, CheckMate-649) and is OUT of this pool. The addressable funnel is therefore incidence × advanced × HER2+ × CPS≥1.
KEYNOTE-811 added pembrolizumab to the trastuzumab + chemotherapy backbone in 1L HER2-positive advanced gastric/GEJ cancer, improving overall survival (HR 0.80; CPS≥1 HR 0.79) and progression-free survival (HR 0.73), establishing chemo-IO + anti-HER2 as the standard for the PD-L1 CPS≥1 majority (~85%). The label and guidelines restrict the regimen to CPS≥1 after the CPS<1 subgroup showed no benefit.
Mandatory at diagnosis: HER2 IHC/ISH (selects the trastuzumab backbone) and PD-L1 CPS (gates pembrolizumab to CPS≥1). HER2-negative disease goes to a different IO regimen (nivolumab) and is OUT of this pool. The addressable pool is HER2+ AND CPS≥1.
Phase 3 randomized double-blind placebo-controlled (n=698): untreated unresectable/metastatic HER2-positive gastric/GEJ adenocarcinoma, pembrolizumab 200 mg q3w + trastuzumab + chemo (FP or CAPOX) vs placebo + trastuzumab + chemo. Dual primary endpoints OS and PFS; restricted to PD-L1 CPS≥1 after the CPS<1 subgroup showed no benefit.
Load-bearing 5/6 sourced. ASSUMED uptake is yours to change.
This indication only, not Keytruda's total revenue
First-line unresectable or metastatic HER2-positive gastric / gastroesophageal junction adenocarcinoma, PD-L1 CPS ≥1, pembrolizumab ADDED to trastuzumab + fluoropyrimidine/platinum chemotherapy (KEYNOTE-811). Pembrolizumab layers onto the trastuzumab+chemo (ToGA) backbone rather than replacing it; the branded Keytruda line is the monetized slice.
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.
$565M
8 modelled markets (US, EU5, JP, CN) · modelled net revenue · 2026 (forecast)
Peak $684M · launch 2021 → 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 1L HER2+ gastric/GEJ slice rises from the 2021 accelerated launch to a ~$0.7B plateau across 2027-28 ≈ ~2% of the franchise, then erodes from ~2028 into the biosimilar cliff. It is small and biomarker-gated (HER2+ AND CPS≥1), with revenue concentrated in the West despite China/Japan holding ~85% of gastric incidence (deeply discounted net prices there). 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 · Beyond that fraction, the headline rests on branded uptake within a pool where the comparator is the bare trastuzumab-plus-chemo backbone, on China reach modelled near 50% against cheaper domestic PD-1s, and on a pembrolizumab-component-only annual net (US ASP ~$11.8k per 200 mg dose) with no indication-specific price published.
The decline is defended, not certain
The decline is well founded, a dated US composition-of-matter expiry around 2028 with the EU following around 2029 on the industry's largest biologic, but mAb erosion is gradual share loss rather than a cliff, and the subcutaneous Qlex formulation approved Sep 2025 is an explicit volume defence whose effectiveness the model can only assume.
What would change our mind
If zanidatamab or an earlier-line trastuzumab deruxtecan regimen displaces trastuzumab as the 1L HER2+ backbone before 2028, pembrolizumab's add-on position rests on a foundation that is being replaced, and the 2027–2028 plateau does not happen even without biosimilar entry.
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 gastric (stomach, C16, incl. cardia/GEJ) cases per year; flat (slow Western decline offset by ageing). Country-specific GLOBOCAN 2022 stomach-cancer incidence (incl. cardia/GEJ); China and Japan dominate (~85% of the 8-market total). Held flat (Western decline offset by ageing/East-Asian burden). | ||||||||||
| × Advanced/metastatic (1L-eligible)est | 45% | 45% | 45% | 45% | 45% | 45% | 30% | 45% | share, not summed | SEER · screening |
Unresectable/metastatic at diagnosis or recurrence, the 1L-systemic-eligible fraction. Lower in Japan (endoscopic screening shifts diagnosis early). ~40-50% of gastric cancer is advanced/metastatic and 1L-systemic-eligible in the West/China; Japan lower (~30%) because endoscopic screening shifts diagnosis to early, curable stages. The single largest cross-market estimate (sensitise widely). | ||||||||||
| × HER2-positiveest | 18% | 18% | 18% | 18% | 18% | 18% | 18% | 18% | share, not summed | ToGA · meta |
HER2-positive (IHC3+ or IHC2+/ISH+); ~18% of advanced gastric/GEJ (ToGA screening 22.1%; GEJ higher than gastric). HER2-positivity is ~15-22% of advanced gastric/GEJ (ToGA 22.1%); modelled at ~18% blended. The HER2 gate that defines the trastuzumab+pembro pool. | ||||||||||
| × CPS≥1, tested & treatedest | 74% | 72% | 72% | 70% | 70% | 72% | 74% | 50% | share, not summed | KN-811 · testing |
PD-L1 CPS≥1 (~85% of HER2+; the label gate) AND HER2/PD-L1-tested, fit for and receiving the regimen. Branded UPTAKE is the share row below. Combines the CPS≥1 gate (~85% of HER2+) with HER2/PD-L1 testing completeness and treatment rate. Net ~0.70-0.74 in the West/Japan (0.85 CPS≥1 × ~0.85 testing/treatment); lower in China (~0.50, testing/access tier-concentrated). Excludes branded UPTAKE. | ||||||||||
| = Addressable 1L HER2+ CPS≥1 pool | 1.9k | 383 | 853 | 833 | 391 | 397 | 5.0k | 15k | 24k | computed |
Incidence × the rates above, advanced HER2+ CPS≥1 gastric/GEJ patients reachable for the trastuzumab+pembro+chemo regimen this year. The 1L HER2+ gastric/GEJ pool is broadly stable, with slow Western gastric decline and rising HER2-testing completeness roughly offsetting, then a slight erosion from ~2028 as 2L HER2 ADCs (T-DXd) and earlier-line competitors divert patients. | ||||||||||
| × Keytruda uptake (branded) | 76% | 57% | 59% | 41% | 41% | 43% | 32% | 19% | 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 | 1.4k | 218 | 505 | 341 | 160 | 169 | 1.6k | 2.8k | 7.2k | 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 |
Until-progression IO: per-patient revenue is the annual net cost of the pembrolizumab component (trastuzumab/chemo are separate). US ASP ≈ $11.8k/200mg q3w (~$205k/yr list) net of ~10-15% GTN → ~$185k/yr. EU nets ~$80-95k. Japan ~$75k (biennial NHI cuts). China NRDL → ~$28k/yr. −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 | $254M | $18.8M | $46.1M | $27.8M | $12.3M | $14.3M | $118M | $74.6M | $565M | 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+ gastric/GEJ (CPS≥1): 8 modelled markets (US, EU5, JP, CN)
Each agent's share of the addressable 1L HER2+ CPS≥1 pool. The branded-pembrolizumab line shows the launch ramp (added to trastuzumab+chemo) to standard-of-care, then the ~2028 LOE biosimilar erosion; the gap below the top line is patients on the bare trastuzumab+chemo backbone, untreated, or (China) domestic PD-1 regimens. The branded pembrolizumab line (IV + SC Qlex) is the only line this model monetizes.
Share of the 24k-patient addressable 1L HER2+ CPS≥1 pool this regimen is modelled to treat, by year
Keytruda is modelled at 30% of this pool in 2026, peaking at 44% 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
Trastuzumab + chemo (ToGA backbone) 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 (30%), 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/reimbursement timing (US accel. 2021 → CPS≥1 2023 → full 2025; EU Aug 2023; China Jun 2024; Japan May 2025); trastuzumab+chemo (ToGA) is the backbone/comparator; domestic Chinese PD-1+trastuzumab take China-only share; pembrolizumab biosimilars timed to the ~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 gastric line
EU biosimilar entry; SC Qlex conversion mitigates IV-biosimilar share loss
Zanidatamab and T-DXd 1L HER2+ readouts could pressure the trastuzumab+pembro backbone
✓ = 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
Even with pembrolizumab + trastuzumab + chemo, median OS in 1L HER2+ gastric/GEJ is ~20 months and most patients progress; CPS<1 patients derive no benefit and are excluded, and HER2 heterogeneity and acquired resistance limit durability. There is no established post-progression IO standard, and 2L therapy relies on T-DXd. That residual sustains development of next-generation HER2 ADCs and bispecifics (e.g. zanidatamab) and novel IO combinations in the upper-GI setting.
The synthesis for this indication, grounded in the cited trial, guideline and access facts above.
Rivals in this setting (1L HER2+ gastric/GEJ)
Swipe to explore →
| Rival / regimen | Developer | Position in this setting | Approved (date, trial, n) | Head start vs this regimen (months) | Source |
|---|---|---|---|---|---|
| Trastuzumab + chemo (ToGA backbone) (Live threat) | Roche/Genentech | Live threatwhyThe established 1L HER2+ backbone (OS 13.8 vs 11.1 mo, HR 0.74) pembrolizumab is ADDED to; the residual for non-IO-triplet (incl. CPS<1) patients. | not in the record | not in the record | ToGA, trastuzumab + chemo 1L HER2+ gastric (Bang, Lancet 2010) |
| Nivolumab + chemo (CheckMate-649) (Ex-US rival) | Bristol Myers Squibb | Ex-US rivalwhyApproved 1L for HER2-NEGATIVE gastric/GEJ, an ADJACENT, non-overlapping segment (HER2+ excluded from the trial); not a rival in this pool. | not in the record | not in the record | CheckMate-649 (1L HER2-NEGATIVE) |
| Trastuzumab deruxtecan (Enhertu) (Watch) | AstraZeneca / Daiichi Sankyo | WatchwhyApproved 2L+ HER2+ gastric (post-trastuzumab), a later-line sequential agent, not a 1L rival; could move earlier and pressure the backbone. | not in the record | not in the record | Bang, Lancet 2010 (ToGA) |
| Zanidatamab (+ chemo ± IO) (Watch) | Jazz / Zymeworks | WatchwhyPhase 3 in 1L HER2+ gastric/GEJ, a future challenger to the trastuzumab+pembro backbone. | not in the record | not in the record | HERIZON-GEA (Ph3, 1L HER2+) |
| Domestic Chinese PD-1 + trastuzumab (China rival) | Innovent / Hengrui / others | China rivalwhyNRDL-listed, far cheaper, structural China 1L HER2+ share pressure for branded Keytruda. | not in the record | not in the record | NMPA / NRDL |
| 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, - | -52 (after) | Keytruda Qlex (subcutaneous) FDA approval (Merck, Sep 2025) |
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 trastuzumab+chemo, dosed 200 mg q3w (or 400 mg q6w) until progression, so per-patient revenue is the annual net cost of the pembrolizumab component (trastuzumab/chemo are separate). 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), added to the trastuzumab + chemo backbone until progression, so per-patient revenue is modelled as the annual net cost of the pembrolizumab component only (the trastuzumab and chemo are separate spend). US ASP ≈ $11,795/200 mg q3w (~$205k/yr list) ⇒ ~$185k/yr net after ~10-15% GTN. EU nets HTA-negotiated (~$80-95k). Japan NHI ~$75k. China NRDL ~$28k (the largest incidence market but deeply discounted). −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 | May 2021 (accel.); Nov 2023 (CPS≥1); 19 Mar 2025 (full) | reference | CPS ≥1 | Trastuzumab + chemo (ToGA) | Accelerated (ORR) 2021 → CPS≥1 restriction 2023 → full approval (OS) Mar 2025. Medicare Part B/commercial; ~10-15% GTN |
| Germany | G-BA / IQWiG | 2023-2024 | ~0.5 yr | CPS ≥1 | Trastuzumab + chemo | EC approval Aug 2023 (CPS≥1 from start); AMNOG net below list; densest EU access |
| France | HAS | 2023-2024 | ~0.7 yr | CPS ≥1 | Trastuzumab + chemo | Early access then reimbursement; SMR important |
| UK | NICE | 2024 | ~1.5 yr | CPS ≥1 | Trastuzumab + chemo | Recommended; confidential PAS |
| Italy | AIFA | 2024 | ~1.5 yr | CPS ≥1 | Trastuzumab + chemo | Class H; managed entry; +regional formulary lag |
| Spain | SEFH / MoH | 2024-2025 | ~2 yr | CPS ≥1 | Trastuzumab + chemo | Financed; +17-region formulary lag |
| Japan | PMDA / NHI | May 2025 (label revision) | ~0.5 yr | CPS ≥1 / PD-L1+ | Trastuzumab + chemo | NHI-listed; very high gastric incidence but lower advanced fraction (screening) and biennial NHI cuts |
| China | NMPA / NRDL | 18 Jun 2024 (full, CPS≥1) | ~1 yr | CPS ≥1 | Trastuzumab + chemo / domestic PD-1 | Largest gastric incidence; NRDL access; cheaper domestic PD-1+trastuzumab competition caps share |
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.