Introduction
The Annual Meeting of the American Society of Clinical Oncology is almost peerless in scope, attracting tens of thousands of clinicians, nurses, and other allied professionals to Chicago for nearly a week of education and dissemination of clinical research.
It’s also one of the premier venues if you follow pipeline projects of your favorite biotechs, as evidenced by the fact that you may have seen a trickle of press releases indicating that your company is presenting at ASCO. You see, the abstract titles were released yesterday, offering the faintest clue as to what will be presented. Every year is a cornucopia of new findings, and it’s one of the events I anticipate the most.
Today, I want to take a deep dive into the oral presentations of the meeting, since these presentations are selected by the abstract committee based on their likelihood of generating the highest impact (and are therefore much smaller in number). Join me as we take a look at what projects have been selected for oral talks, as well as what might make them an exciting catalyst.
NOTE: I will not be focusing on poster presentations in this report, as they number in the hundreds and tend to be lower impact or very preliminary. That’s not to say that important information won’t be presented in the posters; it’s just that combing through all of those can be much trickier, and I will tackle exciting findings there on a more limited, company-focused basis.
This article will be organized session by session, in chronological order for the most part. The only exception there will be the plenary session, which is one of the more exciting pieces of the entire meeting. Note that this is not an exhaustive listing of all the abstracts, but more ones that focus on potentially actionable news in the biotech realm or ones that are of particular clinical interest.
Plenary Session – June 2 at 1 PM CT
The plenary session, as usual, will highlight four abstracts expected to have some of the most practice-informing or anticipated data from all the studies.
First is LBA1, focusing on the ESOPEC trial, which is attempting to answer the question about what the best chemotherapy (with or without radiation) protocol is for patients with esophageal cancer that can be removed with surgery. This does not have specific implications for any companies, but it does have important considerations for other trials looking for the best “backbone” of therapy to include in future trials of novel agents.
LBA2 focused on Bristol Myers Squibb’s (BMY) venerable combination of nivolumab plus ipilimumab as therapy given before surgery (compared with nivolumab alone AFTER surgery, the standard of care) for patients with stage III, resectable melanoma. This is expected to provide a definitive answer to a long-raging debate about how best to use immunotherapy for patients with operable melanoma, and I expect we’ll see more evidence for “neoadjuvant” immunotherapy being a best-of-care approach, building on the phase 2 SWOG S1801 study published in the New England Journal of Medicine a few years ago.
LBA3 focuses on comparing in-person vs telehealth early palliative care for patients with advanced lung cancer. I’m not sure what to expect from this one, honestly.
LBA4 focuses on findings from the phase 3 LAURA trial, focusing on AstraZeneca’s (AZN) EGFR inhibitor osimertinib in the setting of EGFR-mutated, stage III non-small cell lung cancer. We had a press release earlier this year indicating “overwhelming” efficacy for osimertinib, so this will likely not be too big a surprise. This continues to build on the story of trials like FLAURA and ADAURA that have moved osimertinib to frontline treatment for metastatic disease and also the post-operative setting for patients who have undergone surgery.
Finally, LBA5 will focus on findings from the ADRIATIC trial, which is assessing the use of the AZN immune checkpoint inhibitors as “consolidation” therapy for patients with early small cell lung cancer. AZN recently issued a press release indicating that this study was positive, as well, and it represents a very important advance for this disease, where there are very, very few treatment options (unlike in NON-small cell lung cancer, where immunotherapy has really advanced everything in a big way).
So this year’s plenary session, overall, looks to be another momentous, exciting display of some of the most exciting research. I’m greatly looking forward to it.
Lung Cancer—Non-Small Cell Metastatic
Trop2 therapies
The oral advanced NSCLC session features a late-breaking abstract presented by Dr Paz-Ares of the EVOKE-01 study, which is comparing the Gilead (GILD) antibody-drug conjugate sacituzumab govitecan against docetaxel in metastatic NSCLC after treatment with chemotherapy and immune checkpoint inhibitors. We know that this study hasn’t quite hit the mark overall from a GILD press release, so it’s going to be important to see the full results.
Another Trop2-directed antibody-drug conjugate, Daiichi Sankyo’s (OTCPK:DSKYF) datopotamab deruxtecan, will be featured in the phase 2 ICARUS-LUNG01 study, focusing on patients with previously treated metastatic NSCLC. Merck (MRK) is also joining the fray with their own Trop2 ADC, sacituzumab tirumotecan, in a presentation of the OptiTROP-Lung01 study.
I will be most interested in seeing the abstract discussion after these first three talks to see how the three Trop2 ADCs appear to be lining up to one another, given that they all feature different payloads.
Other targeted and immunologic therapies
The second half of the session focuses on targeted therapy, with a five-year update of the CROWN study, testing Pfizer’s (PFE) lorlatinib against crizotinib in ALK-positive metastatic NSCLC.
We’ll also be getting a few updates on Johnson and Johnson’s (JNJ) amivantamab, one being a biomarker analysis from the MARIPOSA trial (assessing first-line amivantamab plus lazertinib for any EGFR mutation), and a late-breaker comparing subcutaneous vs intravenous amivantamab, both in combination with lazertinib. If subcutaneous amivantamab is similar in efficacy, it might solve the issue of highly troublesome infusion reactions that are associated with the drug, so this study has important implications for practice.
A final abstract for the session will focus on the Summit Therapeutics (SMMT) PD-1/VEGF bispecific antibody ivonescimab, with data from the phase 3 HARMONi-A trial being presented.
Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Roche’s (OTCQX:RHHBY) atezolizumab is going to feature in two different “BEAT” trials, one focused on advanced small cell lung cancer, and the other a late breaker in malignant pleural mesothelioma. The latter of these cancers lacks almost any treatment options, so that might be an important win for the field.
Melanoma/Skin Cancers
The first abstract of the session will showcase final results from COMBI-AD, a long-running trial supporting the use of Novartis’s (NVS) dabrafenib/trametinib combo in patients with BRAF-mutated, stage III melanoma. We will also see a presentation of a newer sequencing study in BRAF-mutant disease, a phase 2 trial called EBIN, assessing first-line nivolumab-ipilimumab vs. the PFE combo encorafenib/binimetinib for patients with metastatic, BRAF-mutated melanoma. I expect this will give a similar picture to what we learned from DREAMseq, which suggested that first-line immunotherapy is the best way to go if it is feasible.
The second presentation is a late-breaking abstract focused on “neoadjuvant” Nidlegy, a cytokine cocktail currently approved in Europe and being developed by the Swiss-Italian biotech Philogen SpA. This abstract will focus on Nidlegy being injected directly into the tumors, comparing that approach to immediate surgery.
Next is a presentation of the RADICAL study, comparing 3M’s (MMM) imiquimod to radiotherapy for patients with complex lentigo maligna.
Then, we have a first presentation of RELATIVITY-048, assessing BMY’s triplet regimen of nivolumab, relatlimab, and ipilimumab for advanced melanoma. This is a very interesting project, given the approval of nivolumab-relatlimab and nivolumab-ipilimumab. If this combination is well tolerated, it could be a standard of care changer.
We’ll also get an update from Iovance’s (IOVA) lifileucel study in combination with pembrolizumab for first-line treatment of melanoma. IOVA recently got the first approval for an adoptive T-cell-based therapy approach in a solid tumor, so all updates are important to see how they’ll continue to develop the story.
Then, the session will turn toward the more exploratory treatment options. First, KEYMAKER-UO2A is a phase 1/2 study assessing various triplet regimens incorporating pembrolizumab for patients with melanoma that has progressed on prior immunotherapy. These combos feature a number of ongoing MRK pipeline candidates, so this will be one to check out for an early look of how they might advance their own immunotherapy story.
Next is a phase 1 update (abstract 9507) focused on Immunocore’s (IMCR) PRAME-CD3 bispecific molecule IMC-F106C, for patients with refractory cutaneous melanoma. Rounding out the session will be a presentation focused on Syntrix’s dual-CXCR1/2 inhibitor SX-682 in metastatic melanoma.
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Chronic myeloid leukemia and Philadelphia-negative MPNs
In focus for patients with CML are the two contenders for managing T315I disease. In LBA6500, primary findings from the ASC4FIRST study, comparing NVS’s asciminib against investigator’s choice in frontline therapy, will be a key highlight. We know that asciminib is associated with earlier landmark molecular responses, but longer-term follow-up is critical to see if the newer, more expensive drug is outperforming the older standbys for the long term.
In abstract 6501, we’ll see long-term follow-up from OPTIC, updating on the use of Takeda’s (TAK) ponatinib for patients with a T315I mutation, one of the most important resistance drivers in CML.
We’re also going to see an update of MANIFEST-2, a combo study of Morphosys’s (MOR) pelabresib in combination with Incyte’s (INCY) ruxolitinib for myelofibrosis. This study was first presented last year at ASH, with clear improvement of spleen size, but not symptom scores. More follow-up should make the picture clearer on whether this agent has long-term prospects, and it factors mightily into the ongoing M&A story as NVS is seeking to take the company over.
Allogeneic transplant and acute leukemias
The first biotech-focused abstract here is 6504, detailing the use of Autolus Therapeutics’ (AUTL) CAR-T cell treatment obecabtagene autoleucel, which is currently in review with the FDA for approval in patients with relapsed/refractory ALL.
Also on deck is a presentation of phase 1 results from the Chinese biotech Curon BioPharma related to CN201, a CD3/CD19 bispecific inhibitor (similar to blinatumomab) in relapsed/refractory ALL.
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
This session will open with abstract LBA7000, comparing PFE’s brentuximab-containing regimen BrECADD against escalated BEACOPP in Hodgkin lymphoma, in a phase 3 study previously showing non-inferiority between the two approaches. BrECADD was found to be better tolerated than BEACOPP, providing hope for a new standard of care in this setting.
Brentuximab vedotin is also the subject of the ECHELON-3 study, presented in abstract LBA7005, assessing its addition to standard R-squared therapy for relapsed/refractory DLBCL.
Next is a presentation of the CLAMP study, a phase 2 trial taking Elevar Therapeutics’ camrelizumab and adding it to a chemo-based regimen for NK/T-cell lymphoma.
Finally, we’ll get an update on the phase 3 SYMPATICO study, taking AbbVie’s (ABBV) ibrutinib-venetoclax combination in mantle cell lymphoma, with a focus on patients with the high-risk TP53 mutation. At ASH 2023, this combo was shown to improve PFS compared with ibrutinib plus placebo, so this will be an important update.
Hematologic Malignancies—Plasma Cell Dyscrasia
Sanofi’s (SNY) isatuximab will feature in the first two presentations in multiple myeloma, assessing two different isatuximab-containing regimens as part of frontline therapy for patients who are not eligible for stem cell transplant. Updated findings in the relapsed setting for GSK’s belantamab mafodotin and JNJ’s cilta-cel will also be featured.
Breast Cancer—Metastatic
CDK4/6 inhibitors feature in the first two late-breakers for this session, first in findings from the phase 3 postMONARCH study, looking at Lilly’s (LLY) abemaciclib in patients after progression on a CDK4/6-containing regimen. The second is an update of the phase 2 Young-PEARL study, looking at PFE’s palbociclib in premenopausal women with metastatic breast cancer.
We’ll also get a look at primary findings from PATRICIA cohort C, adding palbociclib to trastuzumab and endocrine therapy for patients with HER2-positive, PAM50 luminal breast cancer.
GILD’s sacituzumab govitecan shows up again in this session, with a late-breaker focusing on a phase 2 trial combining this Trop2 ADC with or without pembrolizumab in metastatic, hormone-positive breast cancer. Daiichi’s datopotamab deruxtecan will also be shown in a report on patient-reported outcomes.
The Seagen (Pfizer) drug enfortumab vedotin will also be explored in abstract 1005, including patients with triple-negative and hormone-positive breast cancer.
Breast Cancer—Local/Regional/Adjuvant
A late breaking abstract will open this session, focusing on findings from the phase 3 A-BRAVE trial, investigating PFE’s PD-L1 antibody avelumab for patients with residual disease after surgery and chemotherapy for early-stage triple-negative breast cancer.
Another late breaker will detail findings from ISPY-2.2, looking at the pathologic complete response rate of datopotamab deruxtecan plus durvalumab as neoadjuvant therapy for breast cancer.
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
This session features early results from different pipeline projects, including the following:
- M9140 – Merck’s entry into the CEACAM5 space, which I would have thought would be rendered defunct by Sanofi’s exit late last year, but they will be giving an update in colorectal cancer here.
- ABBV-706, an ABBV-developed SEZ6-targeted ADC in advanced solid tumors. This is the first I’m hearing of this target, so it will be interesting to check this out.
- DEP CTX, a modified version of cabazitaxel being developed by Starpharma (OTCQX:SPHRF), in advanced solid tumors.
- A phase 1 readout of PFE’s KAT6 inhibitor PF-07248144 in advanced solid tumors (first-in-human data previously presented in a poster at ASCO 2023).
- A report of LLY’s novel KRAS G12C inhibitor olomorasib in KRAS G12C-mutated advanced solid tumors.
- A report on the combination of the SHP2 inhibitor JAB-3312 and the KRAS inhibitor glecirasib (both developed by Jacobio (OTCPK:JBPHF).
There’s not much to say about these agents, and these early readouts are likely to be encouraging, though not definitive. Something to watch on the horizon, though, as you look for ideas in the biotech sector.
Developmental Therapeutics—Immunotherapy
There’s also a session devoted to early findings of trials focused on immunotherapy in cancer. Here are the highlighted pipeline candidates on display:
- Adaptimmune’s (ADAP) lete-cel, a CAR-T cell therapy directed against NY-ESO1, with prior data presentations being expected to be sufficient for approval, as I covered in a recent article
- The CarsGen (OTCPK:CRTHF)-developed Claudin-18.2 CAR T-cell therapy in GI cancers will be featured in a final phase 1 study results presentation
- Phase 1/2 results of the EGFR/CD28 bispecific molecule REGN7075 (developed by Regeneron (REGN) in combination with cemiplimab for advanced solid tumors
- A first-in-human study of FS222, a next-generation PD-L1/CD137 bispecific being developed by F-star Therapeutics in partnership with Takeda
- Findings from the phase 1 DRAGON study investigating the Scholar Rock (SRRK)-developed TGF-beta1 inhibitor linavonkibart in patients with anti-PD-1-resistant advanced solid tumors
- Medicenna’s (OTCQB:MDNAF) IL-2 agonist MDNA11 will be presented in results from the ABILITY-1 trial
Genitourinary Cancer—Prostate, Testicular, and Penile
The first talk here is a late breaker focusing on SNY’s cabazitaxel, to see if it adds to benefit from abiraterone after developing extensive disease following docetaxel treatment for patients with metastatic prostate cancer.
LLY’s CDK4/6 inhibitor abemaciclib is also the subject of the CYCLONE 2 trial, taking a look at adding this agent to abiraterone in mCRPC.
Genitourinary Cancer—Kidney and Bladder
Two presentations will highlight different outcomes from the use of PFE’s enfortumab vedotin, which was the subject of a major win earlier this year in advanced bladder cancer. No doubt, the fortunes of this molecule play significantly on PFE’s advancing story and the success of the Seagen acquisition.
The session will also feature various data updates and biomarker analyses of important immunotherapy-based combination trials in kidney cancer, although not much that momentous or new.
Gynecologic Cancer
The session will open with a late breaker focused on findings from a randomized phase 2 trial investigating BMY’s nivolumab with or without ipilimumab in ovarian and non-renal clear cell carcinomas.
The KEYVIBE-005 study is another late breaking abstract, this one evaluating the coformulation of MRK’s vibostolimab and pembrolizumab for previously treated, MMR-deficient endometrial cancer.
Gastrointestinal Cancer—Colorectal and Anal
One abstract of interest from this session will focus on NEOPRISM-CRC, a study of MMR-deficient/MSI-H stage II or III CRC where use of pembrolizumab before surgery is stratified to tumor mutational burden, helping to further refine treatment selection in this setting and hopefully identify patients who can safely forgo the surgery needed to remove their cancers.
Later in the session, the Arcus Biosciences (RCUS) agent etrumadenant will be discussed in the context of previously treated metastatic CRC. This is an interesting presentation for me, since I have focused my attention in past articles mainly on their anti-TIGIT project.
Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
Following on mixed results from perioperative immunotherapy for anti-PD-(L)1 therapies, EA2174 is going to be looking at perioperative nivolumab plus ipilimumab in locoregional esophagogastric cancers, hopefully with better results than we’ve seen from MATTERHORN and the KEYNOTE trial.
Nivolumab-ipilimumab is also going to be featured in CheckMate 9DW, which was previously announced to be better than first-line TKIs for advanced HCC, but it’s going to be incredibly important to see if it’s clearly better than something like the STRIDE or IMbrave150 regimens.
Pediatric Oncology
The recently approved RAF inhibitor tovorafenib being developed by Day One Biopharmaceuticals (DAWN) is going to be featured in the pediatric oncology I session, focused on treatment in relapsed/recurrent low-grade gliomas and other MAPK pathway-activated tumors.
JNJ’s FGFR inhibitor erdafitinib will be the subject of the RAGNAR trial, which enrolled patients with FGFR-altered solid tumors.
Central Nervous System Tumors
The Apollomics (APLM) compound vebreltinib will be the focus of a presentation in this session. This c-MET inhibitor is being investigated in a phase 2/3 trial of previously treated, secondary glioblastoma or IDH-mutated glioblastoma and a specific gene fusion.
We’ll also get a report of the failed Kintara Therapeutics (KTRA) trial for their compound VAL-083.
Finally, we’ll have a look at the EF-25 trial, assessing the use of Novocure’s (NVCR) tumor-treating fields for patients with non-small cell lung cancer-associated brain metastases. This trial was previously announced to have met its primary endpoint, so it could be an extremely important inroad to advancing the tech further after last year’s LUNAR trial failed to show that tumor-treating fields were really a game changer in lung cancer (so far).
Sarcoma
First up for the sarcoma session is a report on the phase 3 MOTION trial investigating Deciphera’s (DCPH) vimseltinib in patients with tenosynovial giant cell tumor. I had a favorable impression of this company’s prospects in an article from earlier this year, so I’m looking forward to see the update.
Ascentage Pharma (OTCPK:ASPHF) will also provide an updated look at their study of olverembatinib in a specific form of GIST.
Rounding out the investigational agent front for me is the presentation on ARTEMIS-002, featuring the anti-B7-H3 ADC HS-20093 (licensed by GlaxoSmithKline (GSK) in patients with refractory osteosarcoma.
Head and Neck Cancer
Elevar Therapeutics will feature prominently in the head and neck session, with the results of the phase 3 DIPPER study detailing the potential benefit of camrelizumab in the adjuvant setting for high-risk, locally advanced nasopharyngeal carcinoma. A similar phase 3 study will be presented for Beigene’s (BGNE) tislelizumab, again in locally advanced nasopharyngeal carcinoma.
Cue Biopharma’s CUE-101 is going to be featured in a presentation of phase 1 findings, focused on dose-escalation and expansion of this immunotherapy candidate. I felt their story was very early, so every update is very important for evolving their thesis.
Conclusion
I appreciate you allowing me to take you on a whirlwind tour of the proceedings anticipated at the big oncology show this year. If you found it helpful, or would like to highlight anything else about these studies, please leave a comment. Also, if there is a poster presentation of particular note you feel is worthy of mention, feel free, and that will give us all an idea of what to look for as the firehose of data opens up in our faces. Thank you again for reading!
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