[Moving Trailer Voice] This Halloween: They always come back....

The latest revival is belantamab mafodotin, FDA approved...again. After being vanquished in DREAMM3, it returned in DREAMM7 and even Daratumumab (in combination with Vd) couldn't overcome this blindingly effective drug (in combination with Vd).

This pod reviews belantamab mafodotin's checkered past and wonders what the sequels may have in store for us.

This week's episode recaps some highlights from ESMO 2025:

1. Destiny-Breast05: T-DXd > T-DM1 in persistent HER2+ disease after neoadjuvant chemo + surgery

2. Keynote-905: Neoadjuvant Enfortumab Vedotin + pembro in cisplatin-ineligible bladder cancer

3. POTOMAC: Durvalumab + BCG in non-muscle invasive bladder cancer

4. IMvigor011: ctDNA-guided adjuvant atezolizumab in bladder cancer

5. Dynamic-III: ctDNA guide de-escalation or escalation of chemotherapy in stage III colon cancer

6. HARMONi-6: an excuse to talk about ivonescimab, a bispecific antibody unlike any other currently FDA approved

IL-2, one of the founding fathers of our current immunotherapy landscape, is discussed.

Maintenance therapy with ICIs (atezolizumab or durvalumab) is already established in extensive stage small-cell lung cancer, but lurbinectedin enters the chat with a recent FDA approval. Next up - tarlatamab?

IMforte (maintenance lurbinectedin + atezolizumab): https://doi.org/10.1016/S0140-6736(25)01011-6

DeLLphi-303 (phase 1b maintenance tarlatamab + ICI): https://doi.org/10.1016/S1470-2045(25)00480-2

Our Landmarks of OncoPharm series returns to discuss PARAMOUNT, a landmark study that helped solidify the role of maintenance pemetrexed in NSCLC.

The long awaited subcutaneous formulation of pembrolizumab is not FDA-approved. We discuss its administration and toxicity & PK differences vs. IV use.

Biotin supplementation can interfere with lots of labs cancer patients get routinely - Who knew? (Ahem, not me.) Link: https://doi.org/10.1200/OP-25-00693

POLARIX 5-year Data: https://doi.org/10.1200/JCO-25-00925

We discuss the ALASCCA study (Adjuvant Low-doseASpirin in Colorectal CAncer

The 2025 World Conference on Lung Cancer just concluded, and there are several notable updates concerning treatment of EGFR-mutated NSCLC.

1. The COMPEL study tries to find the value of continuing osimertinib (with the addition of chemotherapy) after progression on osimertinib. The results are, well, compelling!

2/3. We now have updates on the OS benefits of osimertinib + chemotherapy (FLAURA2) and amivantamab + lazertinib (MARIPOSA) compared to osimertinib monotherapy in initial treatment of metastatic disease.

4. NEOADAURA tries to determine if neoadjuvant osimertinib has value, but longer follow-up will be needed to assess this practice.

The 5-year+ follow-up from CARTITUDE-1 has people asking if cilta-cel can cure multiple myeloma? We discuss this data and the broad comparison to the other BCMA-targeting CAR-T product, idi-cel and a recent comparison on plasma cell leukemia.

CARTITUDE-1 Long-Term F/U: https://doi.org/10.1200/JCO-25-00760

Cilta-cel & ide-cel in plasma cell leukemia: https://doi.org/10.1182/bloodadvances.2025016966

The potential breakthrough in RNA vaccine technology has been increasingly discussed on social media. This episode looks at one promising study and its early, early results so far.

UF GBM study: https://doi.org/10.1016/j.cell.2024.04.003

RNA Treatment Vaccine Review: https://doi.org/10.1002/ctm2.1384