Signals Inbox·August 27, 2026·Biopharma

Who is working on pancreatic cancer now?

Revolution Medicines is leading the pancreatic-cancer race right now, with Astellas, Novocure, BioNTech and Genentech, Verastem, RenovoRx, Anocca, ClearNote Health and Immunovia building serious positions across KRAS drugs, vaccines, cell therapy, drug delivery and early detection.

Q1Why has pancreatic cancer become a much bigger drug race now?

Pancreatic cancer has become a much more serious drug race because RAS is finally druggable, a new targeted therapy has already won FDA approval after a large survival trial, and several competing programs have now reached late-stage testing.

When we talk about pancreatic cancer here, we are mainly talking about pancreatic ductal adenocarcinoma, or PDAC. According to the National Cancer Institute, pancreatic adenocarcinoma accounts for roughly 90% to 95% of pancreatic cancers. It is also the disease behind most of the terrible survival statistics associated with pancreatic cancer.

The big change is RAS. More than 90% of PDAC tumors carry a KRAS mutation, yet drug developers spent decades struggling to attack that biology directly. Revolution Medicines has now broken through with Rasonque, or daraxonrasib. At the same time, Astellas has taken a KRAS G12D protein degrader into Phase 3, Revolution Medicines has another G12D drug in Phase 3, Verastem has moved a separate G12D program into a registration-directed study, and Lilly and Genentech are running their own programs.

Other approaches are moving too. Novocure has an approved wearable treatment for locally advanced pancreatic cancer. BioNTech and Genentech are testing a personalized cancer vaccine after surgery. RenovoRx recently completed enrollment in a Phase 3 study that tries to deliver chemotherapy directly to the tumor. ClearNote Health and Immunovia are trying to find pancreatic cancer earlier through blood tests.

A few years ago, many of these ideas were small experiments. Today, several have reached the point where they can realistically change treatment.

Q2Which companies have actually changed pancreatic cancer treatment already?

Currently, Revolution Medicines and Novocure have the strongest recent evidence of actually changing pancreatic cancer treatment, while Partner Therapeutics has an approved targeted drug for a much smaller molecular subgroup.

The biggest move comes from Revolution Medicines. The FDA has now approved Rasonque for metastatic pancreatic adenocarcinoma after prior systemic treatment or for patients who cannot receive multiagent therapy. In the 500-patient randomized RASolute 302 trial, median overall survival reached 13.2 months with Rasonque versus 6.7 months with standard chemotherapy. Median progression-free survival doubled from 3.6 to 7.2 months, and the response rate rose from 11% to 30%.

Novocure reached a different part of the disease with Optune Pax. Its PANOVA-3 trial enrolled 571 patients with locally advanced pancreatic cancer and tested tumor treating fields alongside gemcitabine and nab-paclitaxel. Median survival increased from 14.2 to 16.2 months. The FDA approved the device, and it has since also received a CE Mark in Europe.

Then there is Bizengri, or zenocutuzumab, originally developed by Merus and now marketed by Partner Therapeutics. It is approved for pancreatic adenocarcinoma carrying an NRG1 fusion after prior treatment. The FDA based the pancreatic indication on 30 evaluable patients, with a 40% response rate. That is useful precision medicine, although NRG1 fusions occur in only a very small slice of PDAC.

Companies that have already changed pancreatic cancer treatment

Q3Is Revolution Medicines the company to beat in pancreatic cancer right now?

Revolution Medicines is currently the company to beat in pancreatic cancer because it has the strongest clinical result in the field and is already trying to extend that advantage into first-line, post-surgery and KRAS G12D treatment.

As seen above, its Rasonque result came from a 500-patient randomized trial rather than a small uncontrolled cohort. The hazard ratio for overall survival was 0.40, which corresponds to a 60% reduction in the risk of death versus the chemotherapy control during the trial. That gives Revolution Medicines a level of evidence most pancreatic-cancer startups are years away from producing.

The company has also built an unusually wide late-stage PDAC program. RASolute 303 is testing daraxonrasib alone and with chemotherapy in previously untreated metastatic pancreatic cancer. RASolute 304 is studying daraxonrasib after surgery and chemotherapy. RASolute 305 is testing zoldonrasib with chemotherapy in first-line KRAS G12D metastatic disease.

That creates a much bigger strategic position than having one successful second-line drug. Revolution Medicines is trying to cover metastatic treatment before and after chemotherapy, resected disease and the largest individual KRAS subtype.

We would put Revolution Medicines clearly ahead of every other pancreatic-cancer drug developer today. The more interesting question now is how much of that lead it can keep.

Q4Has Rasonque actually solved KRAS in pancreatic cancer?

Rasonque has proved that broad RAS inhibition can work in pancreatic cancer, but the treatment still leaves a huge amount of disease uncontrolled.

The RASolute 302 numbers make both sides clear. A 30% response rate is a major improvement over the 11% chemotherapy control, yet roughly seven in ten patients still did not achieve an objective tumor response. Median progression-free survival was 7.2 months. Median overall survival was 13.2 months.

So the bar has moved. Drug developers no longer need to prove that direct RAS treatment is possible in PDAC. They need to keep the cancer controlled for longer, catch resistant tumor cells, combine RAS drugs intelligently or use them earlier in the disease.

That is already shaping the next wave of research. Revolution Medicines is testing combinations and earlier-line use. Genentech has just partnered with IDEAYA to combine a KRAS G12D inhibitor with a PRMT5 inhibitor in tumors carrying both G12D and MTAP deletion. Verastem is attacking RAS-driven signaling and resistance through several different mechanisms.

Rasonque therefore looks more like the start of a competitive RAS era than the end of the pancreatic-cancer problem.

Q5Why is KRAS G12D suddenly so crowded in pancreatic cancer?

KRAS G12D is now the busiest single target in pancreatic cancer because it appears in roughly 40% of PDAC tumors and several companies finally have drugs capable of going after it directly.

We can already identify at least five serious drug programs at different stages. Revolution Medicines has zoldonrasib in a global Phase 3 first-line study. Astellas is recruiting a 614-patient Phase 3 study of setidegrasib. Lilly's MOONRAY-01 trial is recruiting patients with KRAS G12D tumors and includes pancreatic-specific cohorts and chemotherapy combinations. Verastem has moved VS-7375 into a registration-directed Phase 2 study. Genentech is developing RG6620 and has recently agreed to test it with IDEAYA's IDE892 in pancreatic tumors that also carry MTAP deletion.

The approaches are different enough to make this more than a race between five similar molecules. Astellas is degrading the mutant protein. Revolution Medicines targets its active state. Verastem's VS-7375 is designed to inhibit both ON and OFF states. Genentech and IDEAYA are already thinking one step ahead by combining G12D inhibition with another vulnerability that appears in a subset of the same tumors.

Revolution Medicines has also shown why companies are willing to crowd into this target. Early zoldonrasib combinations produced very high response rates, including 82% with modified FOLFIRINOX in one early cohort. We should be careful with that number because the cohort was small and non-randomized. Its real importance is that the result was strong enough to push the program directly into a global Phase 3 trial.

Leading KRAS G12D programs in pancreatic cancer

Q6Can Astellas actually catch Revolution Medicines in pancreatic cancer?

Astellas has probably become Revolution Medicines' most credible direct challenger in KRAS G12D pancreatic cancer, although it still has a lot more to prove clinically.

Setidegrasib is interesting because Astellas is trying to destroy KRAS G12D rather than simply block it. The drug recruits the cell's protein-disposal machinery to degrade the mutant protein. It is the first protein degrader targeting a KRAS mutation to reach Phase 3.

The scale of the trial shows how seriously Astellas is pursuing it. The current Phase 3 study plans to enroll 614 people with previously untreated metastatic pancreatic cancer and adds setidegrasib to either mFOLFIRINOX or NALIRIFOX. Recruitment has expanded across centers in the United States, Japan and other markets.

Astellas still trails Revolution Medicines on evidence. Revolution Medicines already has randomized survival data, a marketed broad RAS drug and a separate G12D program in Phase 3. Setidegrasib still has to show that its elegant mechanism turns into better survival.

If degradation produces deeper or longer KRAS suppression, though, the competitive gap could close quickly. We currently see Astellas as the strongest challenger rather than a co-leader.

Q7Is chemotherapy still doing most of the work in pancreatic cancer?

Chemotherapy is still doing most of the work in pancreatic cancer, and nearly every major new first-line program currently depends on it.

Look at how the late-stage trials are designed. Revolution Medicines is adding zoldonrasib to standard chemotherapy in RASolute 305. Astellas is adding setidegrasib to mFOLFIRINOX or NALIRIFOX. Novocure's approved Optune Pax is used alongside gemcitabine and nab-paclitaxel.

Verastem offers another example. Its RAMP 205 study combines avutometinib and defactinib with gemcitabine and nab-paclitaxel in first-line metastatic PDAC. In the 29-patient recommended-dose cohort reported in June 2026, 52% of patients had a confirmed objective response, 83% experienced some tumor shrinkage and 86% were alive at six months. Those are interesting early numbers, but the cohort remains small and lacks a randomized control arm.

Rasonque has shown that a targeted oral drug can outperform chemotherapy after prior treatment. First-line pancreatic cancer is a tougher test. For now, developers are mostly trying to make chemotherapy work better rather than remove it from the treatment sequence.

Targeted therapy has finally arrived in PDAC. Chemotherapy is still the base layer underneath much of it.

Q8Are pancreatic cancer vaccines finally starting to work?

Pancreatic-cancer vaccines are producing real immune responses and some unusually durable remissions, but we still do not know whether a vaccine can reliably stop recurrence after surgery.

The strongest program remains BioNTech and Genentech's personalized mRNA vaccine autogene cevumeran, originally studied with researchers at Memorial Sloan Kettering. In the small Phase 1 study, eight of 16 vaccinated patients developed strong vaccine-induced T-cell responses. At a median follow-up of 3.2 years, median recurrence-free survival had still not been reached in those responders, compared with 13.4 months in patients who did not mount the same immune response.

The biology was surprisingly durable. A Nature follow-up estimated a median lifespan of 7.7 years for the vaccine-induced T-cell clones, and most of those clones could still be detected roughly three years after vaccination.

The problem is the sample size. Sixteen vaccinated patients cannot establish a standard of care, and the patients were not randomized according to whether their immune systems responded. Genentech is now recruiting the 260-patient randomized IMCODE003 Phase 2 study, which compares autogene cevumeran plus atezolizumab and mFOLFIRINOX with chemotherapy alone after pancreatic-cancer surgery. That trial is the real test.

Elicio Therapeutics shows why we should stay demanding. Its randomized Phase 2 AMPLIFY-7P trial of ELI-002 7P failed its prespecified disease-free-survival endpoint across the full study population. A post-hoc analysis of patients whose tumors had been completely removed looked better, with median disease-free survival of 23.8 versus 12.8 months, but that finding needs confirmation.

Elicio has since reported another intriguing observation: three patients who progressed after ELI-002 and later received nivolumab-based therapy achieved complete radiographic and metabolic responses. The company is now planning to test combinations involving ELI-002, RAS inhibition and checkpoint therapy. We would treat that as a reason to keep watching Elicio, rather than evidence that the vaccine already works.

Q9Can engineered T cells really work in pancreatic cancer?

Engineered T cells can clearly attack pancreatic cancer in some patients, but current TCR-T therapy is still far too narrow and difficult to manufacture to work for most people with PDAC.

A recent Phase 1/2 study gives us one of the clearest examples. Researchers treated five patients with recurrent pancreatic cancer using their own T cells engineered to recognize KRAS G12V. One patient with liver metastases achieved a complete response lasting 5.5 months, while two others had short periods of stable disease.

That is a small study, but eliminating visible metastatic pancreatic cancer in even one patient is biologically meaningful. The less encouraging part came with repeat treatment. Additional TCR-T infusions failed to produce new responses, and two patients showed evidence of very rapid immune rejection of the engineered cells.

The eligibility problem is also severe. The treatment in that study required both a KRAS G12V tumor and a particular HLA type, HLA-A*11:01. A patient can therefore carry the right cancer mutation and still be unable to receive the therapy.

Companies are now trying to build a broader platform around this idea. Anocca has begun treating pancreatic-cancer patients with ANOC-001, its KRAS G12V TCR-T therapy, and is building additional products against KRAS mutations. AstraZeneca is also studying engineered T cells against KRAS G12D.

TCR-T is currently one of the most exciting proof-of-concept areas in pancreatic cancer. We still do not really know whether it can become a practical treatment for thousands of patients rather than a highly personalized option for carefully selected ones.

Q10Is Novocure really a pancreatic-cancer leader now?

Novocure deserves to be considered a pancreatic-cancer leader today because Optune Pax has already passed the test that wipes out most experimental oncology ideas: a large randomized trial showed patients lived longer.

The mechanism is unusual. Optune Pax sends alternating electric fields through adhesive arrays placed on the abdomen. These tumor treating fields interfere with processes cancer cells need to divide. Patients carry a portable generator and receive the treatment while going about daily life.

PANOVA-3 enrolled 571 people with locally advanced pancreatic cancer. Adding Optune Pax to gemcitabine and nab-paclitaxel increased median overall survival from 14.2 to 16.2 months. The FDA described the improvement as approximately two months when it approved the device.

The pain result was also strong. Novocure reported median time to pain progression of 15.2 months with Optune Pax versus 9.1 months with chemotherapy alone. For a cancer where quality of life can deteriorate quickly, six additional months before pain progression is clinically relevant even if the survival gain looks modest beside Rasonque's.

Novocure also gives the field a mechanism completely separate from KRAS, vaccines or immune cells. That could become increasingly useful if future pancreatic-cancer treatment relies on combining approaches that attack tumors in different ways.

Q11Can RenovoRx make old chemotherapy work better?

RenovoRx has one of the more credible attempts to improve pancreatic cancer without inventing a new cancer drug: it is trying to put much more chemotherapy where the tumor actually is.

Its Trans-Arterial Micro-Perfusion platform uses the RenovoCath device to deliver gemcitabine through arteries supplying a locally advanced pancreatic tumor. The Phase 3 TIGeR-PaC study compares this targeted delivery strategy with systemic treatment.

RenovoRx recently completed enrollment, so the project has moved beyond the constant recruitment risk that kills many small biotech trials. The company reported that 78 of the 86 deaths required for the event-driven final analysis had occurred when enrollment closed. Topline survival data are expected after the remaining events and trial follow-up.

There is already some evidence that the delivery system changes drug exposure. In a pharmacokinetic substudy, researchers estimated that roughly 51% of the intra-arterially delivered gemcitabine was extracted around the targeted area before reaching systemic circulation. The approach produced lower systemic exposure despite using a higher local drug concentration.

That is exactly what RenovoRx is supposed to do. The unresolved question is whether better local drug delivery gives patients more time. The Phase 3 survival result will decide whether RenovoRx becomes an important pancreatic-cancer company or simply a clever delivery experiment.

Q12Who is closest to finding pancreatic cancer earlier?

ClearNote Health and Immunovia currently have two of the most developed pancreatic-focused blood tests, while academic biomarker teams are producing results good enough to keep the race open.

ClearNote's Avantect Pancreatic Cancer Test has recently been validated in an independent cohort of 1,445 people with elevated risk factors. The company reported 82.6% overall sensitivity, 76.8% sensitivity for stage I and II disease and 97.5% specificity. Additional validation cohorts included people with new-onset type 2 diabetes, one of the groups being studied for higher pancreatic-cancer risk.

Immunovia's PancreaSure takes a different biomarker approach. In the 1,066-sample CLARITI validation study, the test detected 78% of early-stage pancreatic cancers with 94% specificity. Immunovia is focusing on people with hereditary or familial pancreatic-cancer risk rather than trying to screen the general population.

Academic researchers are close enough that we should not assume a commercial company has already won. A Penn and Mayo Clinic team has studied a four-marker panel combining ANPEP, PIGR, CA19-9 and THBS2. The research cohort showed 87.5% detection of stage I and II pancreatic cancers.

These percentages cannot be ranked as if the tests were run head-to-head. The cohorts, risk profiles and study designs differ. Several independent approaches are now repeatedly detecting a large majority of early pancreatic cancers in selected populations, which is much more convincing than one unusually good study.

Leading pancreatic-cancer early-detection approaches

Q13Could early detection save more lives than another pancreatic-cancer drug?

A blood test that reliably finds pancreatic cancer before it spreads could eventually have a bigger population-level effect than most new drugs currently in development.

The reason is visible in SEER data. About 15% of pancreatic cancers are diagnosed while still localized, and five-year relative survival in that group is 43.6%. Roughly 51% are already metastatic at diagnosis, where five-year survival falls to 3.4%.

That is almost a thirteenfold survival gap.

Moving even part of that 51% metastatic group toward earlier diagnosis could therefore create an enormous benefit. A new metastatic treatment usually has to fight aggressive disease that has already spread through the body. Early detection can potentially change whether surgery is possible in the first place.

The difficulty is false positives. Pancreatic cancer remains too uncommon across the whole population to tolerate a screening test that sends large numbers of healthy people into invasive scans and procedures. A specificity of 94% or even 97% sounds excellent until millions of low-risk people are tested.

That explains why ClearNote and Immunovia are currently concentrating on higher-risk groups such as people with genetic predisposition, strong family history or new-onset diabetes. The early-detection race may ultimately have the biggest upside in pancreatic cancer, but broad population screening still looks much further away than targeted screening.

Q14Do rare pancreatic-cancer mutations still matter now that broad RAS drugs work?

Rare mutations still matter in pancreatic cancer because better treatment is actually making molecular testing more useful, not less useful.

Bizengri is the clearest example. The drug targets NRG1 fusion-positive cancers and has FDA approval in previously treated advanced pancreatic adenocarcinoma. The pancreatic efficacy dataset was only 30 evaluable patients, but 40% responded. For someone whose tumor carries an NRG1 fusion, that tiny biological subgroup can completely change the treatment menu.

BRCA1, BRCA2 and related DNA-repair mutations are another established case. These alterations occur in a minority of pancreatic cancers, but they can influence the use of platinum chemotherapy and, in selected patients, PARP-inhibitor maintenance.

The precision is getting even finer now. Genentech and IDEAYA are preparing a combination for patients whose tumors carry KRAS G12D and an MTAP deletion at the same time. A patient may therefore move from being classified simply as “pancreatic cancer” to “KRAS G12D pancreatic cancer” and then to an even smaller subgroup defined by a second alteration.

Broad RAS inhibition gives doctors a treatment that covers a much larger share of PDAC. Alongside it, increasingly specific drugs are carving the disease into smaller groups where a particular vulnerability can be exploited.

That makes comprehensive tumor profiling more valuable these days, especially as the number of actionable subgroups grows.

Q15So who is actually leading pancreatic cancer research now?

Revolution Medicines is currently leading the therapeutic race in pancreatic cancer, while Astellas, Novocure, BioNTech and Genentech, RenovoRx, Verastem, Anocca, ClearNote Health and Immunovia are each building credible positions in different parts of the disease.

Revolution Medicines has the clearest lead because it combines three things nobody else currently has together: a large randomized survival win, an FDA-approved broad RAS drug and multiple Phase 3 programs that can move the same biology into earlier treatment settings. Its biggest near-term rival is Astellas, whose setidegrasib program could make protein degradation a serious alternative to conventional KRAS inhibition.

The KRAS race is getting much wider behind them. Verastem has already pushed VS-7375 into a registration-directed pancreatic study. Lilly's G12D program is recruiting hundreds of patients across solid tumors. Genentech is already testing how to combine G12D inhibition with another molecular weakness through its new IDEAYA collaboration.

Novocure occupies a different position because it has already produced a survival benefit without targeting a mutation at all. BioNTech and Genentech have probably the most important cancer-vaccine test underway after surgery. RenovoRx is approaching a Phase 3 answer on targeted chemotherapy delivery. Anocca and other TCR-T groups are trying to turn isolated cell-therapy responses into something reproducible.

Early detection could eventually matter even more. ClearNote Health and Immunovia have blood tests with meaningful validation data in higher-risk populations, and academic groups are still competitive enough that there is no obvious winner yet.

The field has become much easier to map. RAS is currently the center of gravity, with Revolution Medicines in front. KRAS G12D is the main competitive drug target. Novocure leads the non-drug treatment branch. BioNTech and Genentech have the most advanced personalized vaccine bet. RenovoRx is the late-stage drug-delivery experiment to watch. ClearNote and Immunovia are among the clearest commercial names in early detection.

Pancreatic cancer remains extremely hard to treat, and most of the experimental approaches discussed here could still fail. But calling the field stagnant now would be wrong. For the first time in years, several completely different approaches have enough human evidence behind them that we can see real competitive races forming rather than a collection of hopeful laboratory projects.