With the American Association for Cancer Research’s annual conference well underway, data from vaccines and other products targeting tough-to-treat cancers have dominated the program.
The American Association for Cancer Research’s annual conference kicks off Friday as more than 20,000 attendees descend on San Diego. Analysts and researchers who spoke with BioSpace said they’re looking forward to early scientific data, and antibody-drug conjugates (ADCs) will be a key focus.
Stay tuned to BioSpace as we keep you updated on all of the biggest data and news from the conference.
Updated: April 10, 12:00 p.m. EST/9:00 a.m. PST
Synthekine Optimistic About Early Safety Signals for IL-2 Treatment
Early results from a Phase Ia/Ib study in advanced solid tumors suggest that Synthekine’s α/β biased IL-2 partial agonist, STK-012, could succeed where other such therapies have failed in terms of toxicities generated by the class.
“The promise of IL-2 in the treatment of solid tumors has yet to be realized as IL-2 analogs developed to date have had limited efficacy and an unacceptable toxicity profile,” Synthekine CMO Naiyer Rizvi said in a statement. He noted that the company has not seen the severe toxicities typically associated with these treatments, “such as hypotension, capillary leak syndrome (CLS) or transaminitis.”
Along with a robust safety profile, the company reported that treatment with STK-012 demonstrated a favorable efficacy, pharmacokinetic and pharmacodynamic profile. Synthekine is studying the drug candidate in a range of solid tumor types, including renal cell carcinoma and non-small cell lung cancer.
Finnish Biotech ‘TILTs’ at Success in Ovarian Cancer
Helsinki-based biotech TILT Biotherapeutics presented data showing that its TILT-123 in combination with Merck’s Keytruda was safe and “demonstrated signs of efficacy” in a Phase I trial in platinum resistant and refractory ovarian cancer patients.
The preliminary data, from 15 patients given intratumoral or intraperitoneal doses of TILT-123—an oncolytic adenovirus armed with tumor necrosis factor alpha and interleukin-2—along with Keytruda, showed 71% disease control in evaluable subjects, TILT reported. One patient with mucinous carcinoma enjoyed a “long-lasting” partial response, the company said, adding that tumor size reductions and significant immunomodulation were seen in injected and non-injected tumors, “indicating the potential for a systemic response.”
TILT’s lead asset, TILT-123 is intended to enhance the efficacy of T-cell therapies, including immune checkpoint blockade or adoptive cell transfer to reinvigorate the tumor microenvironment.
Merck, Kelun-Biotech Present Promising Data from ADC in Gastric Cancer
A TROP2-directed antibody-drug conjugate (ADC) developed by Merck and Kelun-Biotech elicited promising disease control and potentially extended survival in heavily pretreated patients with gastric or gastroesophageal junction cancer, according to an abstract presentation Tuesday at AACR.
Treatment with the ADC, dubbed SKB264, led to a 22% objective response rate in 41 evaluated patients, nine of whom had a partial response. Disease control rate was 80.5%, with a median duration of response of 7.5 months, according to the presentation. In a subgroup of 24 patients who had previously been exposed to at least two lines of therapy, median progression-free survival was 3.7 months and median overall survival (OS) was 7.6 months. The 12-month OS rate was 32.6%.
SKB264 targets the TROP2 cell surface protein, a well-validated target in gastric cancer associated with poor prognosis.
Jordi Rodon, the study’s lead author and associate professor of investigational cancer therapeutics at MD Anderson Cancer Center, noted that by using a different linker-payload combination, “We did not see the interstitial lung diseases associated with other ADCs.”
ALX and Investigators ‘Encouraged’ by Phase I/II R/R B-NHL Data
ALX Oncology presented what it called “encouraging” data Tuesday from a Phase I/II trial of evorpacept in combination with standard rituximab and lenalidomide in patients with indolent and aggressive relapsed or refractory B cell non-Hodgkin lymphoma (R/R B-NHL).
The data, from 20 patients with indolent and aggressive disease, showed a best overall response rate of 94% and a complete response rate of 83%, ALX announced. The median duration of response was not reached. The company additionally reported that the combination regimen was well tolerated, with no dose-limiting toxicities. Importantly, there were no reported treatment-related deaths on study.
“While standard frontline treatments have shown benefit in the indolent B-NHL setting, many patients are likely to see their disease progress after initial treatment,” Paolo Strati, assistant professor of Lymphoma-Myeloma at The University of Texas MD Anderson Cancer Center and the trial’s lead investigator, said in a statement, adding that ALX’s regimen showed an “encouraging response” in this patient population.
“These initial results reinforce evorpacept’s differentiated drug design that has resulted in anti-cancer activity while minimizing hematologic toxicities inherent to other CD47 blocking agents,” Sophia Randolph, CMO at ALX, said in the same announcement.
So Far So Good for Obsidian’s TIL Therapy in Metastatic Melanoma
Obsidian Therapeutics presented positive data from a Phase I study of its tumor-infiltrating lymphocyte (TIL) cell therapy OBX-115 in ICI-resistant metastatic melanoma.
The 25-week data showed the therapy was well-tolerated with no dose-limiting toxicities and no Grade 4 or higher non-hematologic events, the Cambridge, Mass.–based company reported. There were no reports of cytokine release syndrome, capillary leak syndrome or ICANS.
OBX-115 induced deep and durable responses with a 50% objective response rate, including a 33% complete response rate. All six treated patients saw a reduction in tumor burden and meaningful disease control for at least 12 weeks after infusion, according to the press release. All patients were alive as of the data readout and median progression-free survival (PFS) had not been reached; six month PFS was 67%.
“The results are particularly encouraging since OBX-115 is the first engineered TIL cell therapy not requiring IL2 co-administration,” Rodabe N. Amaria, professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and the study’s principal investigator, said in a statement.
AstraZeneca’s ATM Inhibitor Shows Promise in Glioblastoma
Glioblastoma (GBM) was a key focus at AACR Wednesday, where AstraZeneca‘s AZD1390 demonstrated a “manageable safety profile” in patients with recurrent and newly diagnosed disease when given in combination with standard-of-care radiotherapy. The asset, an ataxia telangiectasia mutant (ATM) kinase inhibitor, showed preliminary efficacy in recurrent glioblastoma patients, according to a press release on the conference’s website.
In Arm A of the trial, funded by AstraZeneca, median overall survival of 12.7 months was observed at doses demonstrating target engagement, according to the release. This is compared to an OS of 6 to 10 months elicited by current standard of care based on previous studies.
Glioblastoma is particularly lethal, with most patients surviving no more than two years after diagnosis, study presenter Jonathan T. Yang of Memorial Sloan Kettering Cancer Center said in a statement.
The ATM cell signaling pathway is activated to help repair the DNA double-strand breaks caused by radiation therapy, the current standard of care for newly diagnosed GBM patients, which impedes the treatment’s effectiveness. An ATM inhibitor impedes this repair, thereby enhancing the cancer-killing effect of radiation therapy, Yang said.
Transgene and NEC Report Positive Phase I Data in Head and Neck Cancer
Transgene and NEC presented “extensive Phase I immunology data” from their neoantigen cancer vaccine TG4050 in the adjuvant treatment of head and neck cancer at AACR Tuesday. All 16 patients treated with the vaccine remain disease-free after a median follow-up of 18.6 months, the development partners announced. This is compared to three patients in the control observation arm who have relapsed.
TG4050 elicited persistent immune responses against multiple targets in several patients, and T cell responses were maintained beyond seven months after the initiation of the treatment, the companies reported.
With the current standard of care, approximately 40% of patients in this indication are expected to relapse within 24 months following surgery and adjuvant therapy, according to the press release.
Phase II of the trial is expected to begin enrolling patients “in the coming weeks,” Transgene and NEC said.
Diakonos Oncology’s Dendritic Cell Vaccine Shows Promise in Glioblastoma
Houston-based Diakonos Oncology announced in a poster presentation at AACR that its dendritic cell vaccine, DOC1021, improved survival compared to standard of care in a Phase I trial in glioblastoma multiforme (GBM) patients.
Interim analysis of the open-label study showed that DOC1021 “substantially increased survival,” well beyond the expected median overall survival of 12.7 months for patients receiving the standard of care, Diakonos reported. This metric has not yet been reached, and 12-month survival among evaluable patients currently is 88%, with 12 of 16 newly diagnosed GBM patients remaining alive. There were no serious adverse events attributed to DOC1021.
“These very encouraging results support our confidence in the potential for our dendritic cell vaccines to significantly improve the lives of patients with the most deadly cancers,” Diakonos CEO Mike Wicks said in a statement.
Vincerx Debuts Data From Lead ADC for Solid Tumors
California-based Vincerx Pharma, which is developing antibody-drug conjugates (ADCs) and small molecule drug conjugates to treat cancer, debuted Phase I data for one of its two lead programs, VIP236, in heavily pretreated patients with metastatic tumors.
Of 15 patients dosed to date, seven have achieved objective stable disease, including tumor reduction, the company reported Monday at AACR. VIP236 was well-tolerated, with no severe or life-threatening diarrhea, “validating the purposeful design of VIP236’s optimized camptothecin payload,” according to the press release.
Vincerx CEO Ahmed Hamdy said in a statement that the data, along with preclinical findings using its technology to improve the efficacy of marketed ADCs Trodelvy and Enhertu, “underscore the power of our platform approach for hematologic malignancies and solid tumors.”
Vincerx’s VersAptx platform allows for the combination of different targeting, linker and payload technologies to develop bespoke bioconjugates to address different cancers, according to the press release. Linkers can be designed to reduce non-specific release of the payload, which in turn, can minimize toxicities.
Dose escalation in the Phase I study is ongoing, and additional Phase I data are anticipated this summer, the company shared.
Poseida Therapeutics CAR-T Therapy Shows 60% Response Rate in Multiple Myeloma
Poseida Therapeutics’ lead CAR-T program produced a clinical response in three out of five, or 60%, of previously BCMA-targeted multiple myeloma patients, the company announced Monday.
P-BCMA-ALLO1, currently in Phase I clinical trials, is an investigational B-cell maturation antigen (BCMA)-targeted allogeneic CAR-T for patients with relapsed/refractory multiple myeloma that has progressed after BCMA-targeted therapy.
The findings provide additional evidence that the therapy “could be an appropriate treatment for a broader range of patients with multiple myeloma, including those with relapsed/refractory disease whose cancer progressed following prior BCMA-targeted therapy,” Syed Rizvi, M.D., chief medical officer at Poseida, said in a statement. The company is also developing an optimal lymphodepletion regimen for CAR-T in solid tumors, P-MUC1C-ALLO1, Rizvi added.
Poseida plans to deliver more data analysis for both candidates in the second half of 2024.
AstraZeneca’s Novel PARP1 Inhibitor Shrinks Tumors in Nearly Half of HRR-Deficient Breast Cancer Patients
A new kind of poly-ADP ribose polymerase 1 (PARP1) inhibitor developed by AstraZeneca assisted in shrinking tumors in 48.4% of people with breast cancers possessing BRCA1/2, PALB2 or RAD51C/D mutations, the company reported Monday at AACR.
In the Phase I/II PETRA trial, funded by AstraZeneca, treatment with 60 mg of saruparib—a selective inhibitor of PARP1—led to an objective response rate was 48.4%, a median duration of response of 7.3 months and a median progression-free survival rate of 9.1 months, according to a news release on the conference’s website.
In a cohort of 141 patients with HRR-deficient breast, ovarian, pancreatic or prostate cancer, adverse events related to saruparib were observed in 76.6% of patients, and 2.1% of patients had a serious adverse event related to the drug.
While blocking PARP1 may be sufficient to prevent DNA repair in HRR-deficient tumors, all FDA-approved PARP inhibitors block both PARP1 and PARP2, which can limit use because of toxicity, Timothy A. Yap, vice president and head of clinical development in the Therapeutics Discovery Division at The University of Texas MD Anderson Cancer Center, said in a statement. “By designing selective PARP1 inhibitors, we have a great opportunity to improve safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy and combinability with other therapies,” Yap said.
BMS Bolsters Recently Accepted Regulatory Application for Krazati/Erbitux Combo with New Data
Bristol Myers Squibb released new data on Monday from a Phase I/II clinical trial of its oral KRAS-inhibitor Krazati (adagrasib) and Eli Lilly’s monoclonal antibody Erbitux (cetuximab) in patients with previously treated KRAS-mutated locally advanced or metastatic colorectal cancer (CRC).
The objective response rate, the primary endpoint for the trial, was 34%, with a median progression-free survival rate of 6.9 months. Median overall survival rate was 15.9 months, while the median duration of response was 5.8 months, BMS reported, with disease control observed in 85% of patients.
The safety profile for the combination was “manageable and consistent” with previous reports and with the recognized safety profile of each drug, according to BMS.
The FDA accepted BMS’s supplemental New Drug Application in this indication in February and set a PDUFA date of June 21, 2024.
“While there has been progress in the treatment of colorectal cancer, there remain groups of patients, such as those with KRAS-mutated cancers, who continue to need new, targeted treatment options,” Anne Kerber, senior vice president, head of late clinical development, hematology, oncology, cell therapy at BMS, said in a statement. “These data highlight the significance of testing and identification of KRASG12C mutations in patients with CRC.”
PDC*line Presents Positive Initial Results for Lung Cancer Vaccine
European biotech PDC*line Pharma unveiled interim results Monday at AACR from a Phase I/II clinical trial of its vaccine, PDC*lung01, in combination with Keytruda and on its own in non-small cell lung cancer (NSCLC).
Combining a high dose of the vaccine with Keytruda produced an “acceptable safety profile,” PDC*line reported. Most treatment-related adverse events were consistent with those of other injection-based vaccines or with what has already been observed in other cancer vaccine clinical trials, according to the company. No other safety concerns were identified.
The Keytruda and PDC*lung01 combination produced an objective response rate (ORR) of 63.2% and a disease control rate (DCR) of 94.7%. Nine-month progression-free survival (PFS) was recorded at 52.1%, with a median PFS of 10.9 months. The vaccine on its own showed “biological activity” in activating an antitumor immune response in 68.4% of patients. Final analysis of the trial in the third quarter of 2024, PDC*line said.
The company is “encouraged by the evidence of immune response observed in patients, which supports the mechanism of action of PDC*lung01 in relation to clinical activity,” PDC*line Pharma CEO Eric Halioua said in a statement.
Geneos Announces Positive Results for Cancer Vaccine and Keytuda Combination
Geneos Therapeutics announced Sunday that a Phase I/II trial investigating a combination of its cancer vaccine candidate GNOS-PV02 with PD-1 inhibitor Keytruda and a DNA plasmid-encoded IL-12 reached the primary endpoints of safety and immunogenicity.
The study, published in Nature Medicine, investigated GNOS-PV02 ‘s use as a second-line treatment in patients with advanced hepatocellular carcinoma who have already been treated with a multi-tyrosine kinase inhibitor. Geneos reported a solid safety profile for the candidate, with all adverse events limited to Grades 1 and 2; there were no dose-limiting toxicities or Grade 3 events recorded. The most common adverse events were injection site reactions. The addition of Keytruda in combination with the vaccine did not decrease safety and tolerability, the company noted. As for efficacy, the immunological analysis confirmed the induction of new T cell responses to vaccine-encoded neoantigens in 100% of patients evaluated.
The overall response rate (ORR) was 30.6%, including three complete and eight partial responses, a result Geneos called “statistically significant.”
“To our knowledge, the GT-30 clinical study provides the first definitive demonstration of a personalized cancer vaccine enhancing clinical response to anti-PD-1 therapy by inducing new, neoantigen-specific T cells which traffic to the tumor,” Ildiko Csiki, chief medical officer of Geneos, said in a statement.
Syncromune Debuts Drug-Device Combo in Prostate Cancer
Florida-based Syncromune presented the first-ever clinical data from SYNC-T, a personalized platform therapy that uses a drug-device combination, in metastatic castration-resistant prostate cancer. Patients in the Phase I study saw an overall response rate (ORR) of 85%—more than double the ORR of 20% to 40% typically seen with standard of care in this patient population, according to the company. There were five complete responses and six partial responses among 13 of 15 evaluable participants, most of whom had bone metastases and had experienced failure with prior therapies. SYNC-T was well-tolerated, with minimal side effects and no significant safety concerns, Syncromune reported.
An in situ therapy, SYNC-T uses a combination of partial tumor lysis and intratumoral immunotherapy. The SYNC-T device activates lysis, which causes tumor cells in the lytic zone to rupture, releasing neoantigens into the tumor microenvironment. Then, SV-102, a fixed-dose multi-target drug, is directly administered into the tumor site to further stimulate the immune system and block mechanisms that suppress the immune response.
Precision’s Antibody Effectively Targets Tregs in Healthy and Cancer Patients
Maryland-based Precision Biologics will present a poster Monday showing that its O-glycan epitope targeting anti-human carcinoma monoclonal antibody candidate, NEO-201, can also target naïve regulatory T cells (Tregs) in both healthy subjects and cancer patients.
The study, which gathered human peripheral blood mononuclear cells (PBMCs) from seven healthy donors and six cancer patients from Precision’s Phase II clinical trial studying NEO-201 in combination with Keytruda in adults with solid tumors, analyzed NEO-201’s ability to recognize naïve Tregs (nTregs) in PBMCs. The analysis showed that NEO-201 recognized fraction I of CD4 T cells in healthy donors, confirming Precision’s earlier findings in PBMCs from cancer patients. The percentage of nTregs in cancer patients was higher than in healthy donors.
Regeneron Touts Durability of Multiple Myeloma Candidate
Regeneron buttressed its regulatory case for linvoseltamab, an investigational bispecific antibody, with the presentation of positive pivotal data from the Phase I/II LINKER-MM1 trial in relapsed/refractory (R/R) multiple myeloma.
After 11 months of follow-up, treatment with the candidate elicited a 71% objective response rate (ORR), with 46% of patients seeing a complete response or better and 62% achieving a very good partial response or better, Regeneron reported. Median times to reach these metrics were eight months and three months, respectively. After 12 months, the estimated probability of maintaining a response was 78%, progression-free survival was 69% and overall survival was 75%. None of these measures were reached, and Regeneron stated that these data “reinforce [a] high response rate that deepens over time in patients with heavily pre-treated multiple myeloma.”
Linvoseltamab’s safety profile in the Phase I/II LINKER-MM1 trial was less positive, with 85% of patients treated with a 200-mg dose experiencing Grade 3 or worse adverse events (AE), Regeneron reported in December 2023. Fourteen patients—12% of the patient population—died due to treatment-emergent AEs, of which 11 were due to infections.
The FDA in February accepted the Biologics License Application for linvoseltamab in fourth-line R/R multiple myeloma. The candidate is also under review with the European Medicines Agency.
BioNTech/Genentech Cancer Vaccine ‘Persistent’ in Pancreatic Cancer
BioNTech and Genentech’s messenger RNA (mRNA) cancer vaccine candidate, autogene cevumeran, or BNT122/RO7198457, continued to show promise in a particularly difficult-to-treat form of pancreatic cancer three years after treatment, according to an oral presentation Sunday at AACR. Specifically, patients with resected pancreatic ductal adenocarcinoma (PDAC) continued to see polyspecific T-cell responses and delayed tumor recurrence.
Persistence of T cells “was associated with a longer median recurrence-free survival in cancer vaccine responders,” BioNTech reported in a press release. The company called the results an “early signal” of the candidate’s potential in this indication. PDAC carries a 5-year overall survival rate of only 8% to 10%.
Autogene cevumeran, being jointly developed by BioNTech and Genentech, is currently being studied in three ongoing Phase II clinical trials in adjuvant PDAC, first-line melanoma and adjuvant colorectal cancer.
Opdivo Shows Promise in Neoadjuvant Pancreatic Cancer
Bristol Myers Squibb’s PD-1 inhibitor Opdivo, when combined with several types of chemotherapy prior to surgery, may improve outcomes for pancreatic cancer patients, a pilot study presented at AACR’s annual meeting on Sunday revealed.
The study observed 24 of the 28 trial participants who were given the Opdivo and chemotherapy combination before surgery and had no grade 2 post-operative fistulas. After two years, the combination led to a median progression-free survival rate of 34.8 months; the median overall survival rate was recorded at 35.1 months. No unexpected safety signals were reported, and the addition of Opdivo did not increase the rates of grade three adverse events.
This is the first trial reported of a PD1 inhibitor in neoadjuvant pancreatic cancer, according to the abstract. A Phase II trial is underway.
Correction (April 10): This story has been updated from its original version to correct that Poseida Therapeutics plans to deliver more data analysis for P-BCMA-ALLO1 and P-MUC1C-ALLO1 in the second half of 2024, as opposed to at AACR. BioSpace regrets the error.
