Enhertu Delays Lung Cancer Progression, Survival Benefit Unproven

AstraZeneca and Daiichi Sankyo's Enhertu delayed lung cancer progression. But early survival results favored the comparison treatment. What does that mean for moving the drug into first-line care?

And Definium's single-dose anxiety treatment wins a second Phase 3. That strengthens the filing case, without settling how supported dosing would work beyond a trial.

Welcome to The Pharma Closeout. I'm Alex Mercer. This is Monday's September 14th edition, arriving Tuesday.

I'm Maya Patel. Whether you're starting your day or catching up at the end, we'll help you make sense of the news. We begin with the new lung cancer results.

Top story: the detailed Enhertu results are here, following the positive headline we covered in August. AstraZeneca and Daiichi Sankyo tested the infused antibody-drug conjugate as a first treatment for advanced HER2-mutant non-small cell lung cancer. For an earlier-line expansion, beating the comparator on progression is a substantial opening. Does DESTINY-Lung04 give them a convincing replacement for pembrolizumab and chemotherapy?

It gives them a progression benefit, with survival pulling against that argument so far. In the Phase 3, median progression-free survival was 14.3 months versus 8.3. That was statistically significant. Overall survival was 29.3 versus 33.1 months at this interim look.

Then the August win has become a much harder positioning problem. Longer disease control matters, but it can't carry a claim that patients live longer. Is that unfavorable survival result strong enough to call harm?

No. It's early, with no formal statistical test. AstraZeneca also reports different treatments after progression, which complicates the comparison without explaining it away. The separate safety concern is lung toxicity: adjudicated interstitial lung disease or pneumonitis affected 20.8% on Enhertu, including four fatal cases at the safety cutoff. Lung toxicity is already a known risk. What's new is its extent here, alongside the unresolved survival comparison. This result isn't a first-line approval.

Moving to our Deal and Pipeline Roundup: Sanofi proposes transferring twenty mature medicines and three plants to Cheplapharm for a 26.4% equity stake. Sanofi would shed those operations while retaining exposure to their future value through the receiving company. The undisclosed total value prevents a clean price comparison.

One geographic limit matters: Lovenox is included, but its US business is excluded from the transfer. Completion is expected in 2027, subject to conditions.

Tyra Biosciences, meanwhile, priced about $400 million in expected gross proceeds from stock and pre-funded warrants, before fees. We covered its oral candidate dabogratinib's clinical update last week. Completing this financing would put substantial funding behind that development effort. We'll return to the expected closing date at the end.

At Cellectis, the change goes deeper than financing. It disclosed Monday that it's exiting internal allogeneic CAR-T development and seeking partners for those programs. The board decided September 11th; existing cell-therapy partnerships continue.

Cellectis is giving up its own clinical oncology development effort. Where does that leave the company?

Preclinical gene editing inside the body, for severe lipid disorders — high triglycerides and cholesterol. Those replacement programs haven't yet supplied clinical evidence.

Cellectis says the reset is designed to extend runway into the second half of 2028. That buys time by changing what the company funds. Its next internally developed clinical story would have to come from a different disease area and an earlier starting point.

Back to the conference: Akeso and Summit now have the HARMONi-2 survival numbers we lacked on September 2nd. Their infused PD-1 and VEGF bispecific, ivonescimab, beat pembrolizumab. A survival win against that comparator strengthens the competitive case. Maya, where does the result apply?

First-line PD-L1-positive advanced non-small cell lung cancer, without sensitizing EGFR or ALK alterations, in a Phase 3 conducted entirely in China. Median survival was 30.8 months versus 22.6, statistically significant. Serious treatment-related side effects were more frequent. The magnitude is now visible; whether it carries into a US population remains unresolved.

Outside oncology, Corbus has an early weight-loss signal for CRB-913, a daily CB1-blocking pill designed to act mainly outside the brain. CANYON-1 was a randomized Phase 1b in adults with obesity. At twelve weeks, the assigned sixty-milligram group had an estimated 5% mean weight reduction, against no change on placebo.

A pill outside the GLP-1 class gives Corbus a distinct development path. But the point of that peripheral design is part of the safety question. What did they actually see?

Among 188 recipients, no serious or severe psychiatric events, and one transient moderate depressive symptom. That's an encouraging early observation, not clearance of psychiatric risk. Efficacy was secondary, and twelve weeks leaves both longer-term safety and weight control open.

Returning to targeted lung treatment: Taiho and Cullinan released the detail behind zipalertinib's REZILIENT3 win. This oral drug was added to chemotherapy in first-line EGFR exon twenty insertion-positive non-small cell lung cancer. It keeps chemotherapy in the regimen, so the added disease control has to be weighed alongside the added treatment burden.

Median progression-free survival was 14.5 months versus 8.5 with chemotherapy alone in the Phase 3. But grade three or higher adverse events reached 87.1%, versus 54.4%. The combination extends disease control with substantially more high-grade events; overall survival is still immature.

Turning to relapsed small-cell lung cancer, Hansoh has the full ARTEMIS-008 results for its infused B7-H3 antibody-drug conjugate, Ris-Rez. Median overall survival was 18.5 months versus 10.3 with topotecan in this China Phase 3, with fewer high-grade treatment-related events.

That's the detail behind the earlier survival announcement. For GSK, which holds rights outside mainland China, Hong Kong, Macau and Taiwan, the licensed program now has a quantified survival case from Hansoh's China trial.

A second B7-H3 conjugate has its own survival result: MediLink and Roche's Tam-Peli, in TAISHAN-302. Another China Phase 3, also against topotecan, in small-cell lung cancer relapsing after platinum. Two distinct drugs improving survival makes the interest in this target less dependent on one program. Can those trials distinguish the drugs?

They can't rank them. Patient groups differ, and the safety definitions differ too. On its own, Tam-Peli showed median survival of 13.3 months versus 9.4, with fewer grade three or higher adverse events. That's a second positive program, not a head-to-head contest.

Next, the BioNTech updates we previewed Sunday. Gotistobart, its CTLA-4 antibody with OncoC4, now has a mature median survival estimate in previously treated metastatic squamous non-small cell lung cancer. That makes the earlier signal easier to interpret. How close is this to pivotal confirmation?

This remains PRESERVE-003's nonpivotal first stage, with only 87 randomized patients. For gotistobart, median survival was 18.5 months versus ten with docetaxel. The pivotal second stage is still running; that's the separate test the development case now rests on.

BioNTech's other weekend update tests a combination: pumitamig, a PD-L1 and VEGF bispecific, plus the B7-H3 conjugate elfetabart drozuntecan. In an early single-arm study, 70.4% of 71 evaluable small-cell lung cancer patients responded.

That puts B7-H3 in a combination strategy alongside the standalone programs we've just discussed. The response signal belongs to this two-drug regimen; those other survival trials can't establish its comparative value.

And its safety figures cover a different population: 193 patients across small-cell and non-small cell disease. Grade three or higher treatment-related events occurred in 23.3%. Non-small cell efficacy remains immature.

One conference result asks whether less treatment can protect cognition. SWOG's Phase 3 MAVERICK tested MRI surveillance with or without preventive brain radiation in small-cell lung cancer after initial therapy. Patients had no brain metastases. Maya, does avoiding radiation preserve cognition without giving up survival?

The cognition result favors surveillance alone. Among 304 patients, it improved cognitive failure-free survival. But the final overall-survival analysis is pending, so the study hasn't established that survival is preserved equally.

This puts a patient cost of preventive treatment into the comparison, even when there isn't visible brain disease to treat. The potential gain here is avoiding some of treatment's cognitive cost, rather than finding a more active drug.

On Regulatory Watch: Amgen says FDA approved shorter monitoring after the first two Imdelltra infusions in extensive-stage small-cell lung cancer. According to Amgen, observation falls to six to eight hours from twenty-two to twenty-four, plus a next-day check including vital signs. DailyMed still showed the older label at our check.

Amgen's announced change may reduce those initial observation visits. How much of the surrounding burden stays?

Amgen says patients still need a caregiver and must stay within one hour of an appropriate healthcare setting for forty-eight hours after each of those doses. Amgen also says later-dose monitoring is unchanged.

And the Pixclara decision we flagged Friday has landed: Telix says FDA approved it. The prescribing information Telix posted covers PET imaging in adults and children one month and older.

This injected radioactive tracer addresses a difficult distinction after glioma treatment: recurrent or progressive tumor versus treatment-related change. It's used alongside other diagnostic evaluations.

Quick note before our second top story today — if The Pharma Closeout is how you close out your day, follow the show on Spotify or Apple Podcasts.

Our second story: Definium has the Panorama result we were waiting for after Voyage. Its single-dose anxiety treatment, DT120, now has a second independent Phase 3 win in generalized anxiety disorder. That's a stronger foundation for its planned filing: the efficacy signal has appeared in another trial, not another analysis of the first one.

Panorama met its primary endpoint with a hundred-microgram dose of lysergide, taken as a dissolving tablet with psychological support. At twelve weeks, scores on the Hamilton anxiety scale fell 9.8 points versus 4.7 with placebo. The difference was statistically significant. Those are group averages, not a promised improvement for each patient.

The low-dose comparison caught my attention. A second study strengthens replication, but with a treatment patients may recognize, expectancy is still a different question. Does the fifty-microgram arm help settle it?

It doesn't settle it. That arm was exploratory and wasn't powered for efficacy; its inclusion can't prove blinding held or rule out expectancy. Definium reported no drug-related serious adverse events. Longer-term durability and the demands of supported dosing remain open.

That support is part of what Definium tested, even though the tablet is taken once. Definium plans a pre-submission FDA meeting in the fourth quarter and a filing in the first half of 2027.

What to watch: Tyra expected that financing to close September 15th, subject to conditions. Pricing is settled; completion wasn't confirmed in our check.

That's the September 14th edition. Thanks for spending part of your day with us.

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