- On the ground in Chicago at this week’s American Society of Clinical Oncology (ASCO) Annual Meeting, 03 – 07 June 2022, Elena Garralda, Director of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch, presented interim safety and efficacy data of the two-part AURELIO-03 phase I/Ib study of novel immunotherapy, SOT101.
- Elena Garralda and Irene Braña were invited as discussants for sessions exploring the development of novel bispecific antibodies and therapeutic targets, respectively.
- Omar Saavedra, a CORE Phase I Investigator at the same Unit, presented two posters on the design and rationale of two first-in-human phase I/IIa studies assessing the efficacy of novel bispecific antibody, AFM24, as monotherapy and in combination with anti-PDL-1 antibody atezolizumab.
Throughout this week’s American Society of Clinical Oncology (ASCO) Annual Meeting, 03 – 07 June 2022, Chicago (IL, USA), Clinical Investigators of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – Caixa, directed by Elena Garralda, presented 15 different studies reporting on the development and promising efficacy of novel targeted therapies and immune-based strategies, as monotherapy or in combination.
In addition to the other VHIO studies covered by VHIO News throughout the 2022 ASCO Annual Meeting, here we highlight just a sampling VHIO-led research that was selected by ASCO to first outing during the meeting, and briefly highlight other contributions:
IL-15 Superagonist SOT101 shows promise as monotherapy and in combination
Interim safety and efficacy data of the AURELIO-03 two-part phase I/Ib dose escalation study of SOT101, a novel agent that has been designed and optimized for its use as a potent immunotherapy, was presented by Elena Garralda, Principal Investigator of VHIO’s Early Clinical Drug Development Group.
“In this two-part phase I/Ib study we assessed the preliminary efficacy and safety of SOT101 as monotherapy, Part A, and in combination with immunotherapy pembrolizumab, Part B, in 51 patients with advanced solid tumors,” says Elena Garralda, lead author of this present study, results of which she presented during an Oral Abstract Session at ASCO 2022 (1).
The AURELIO-03 investigators sought to confirm the synergistic effects of SOT101 and anti-PD-1 antibody, pembrolizumab, that have been previously validated in various tumor mouse models, inducing a protective memory response. By activating white blood cells SOT101 triggers the immune system, principally T cells or NK cells, to kill tumor cells. Preliminary results show that the SOT101-pembrolizumab combination (Part B of this study) achieved clinical benefit in 63% patients, including those who had not received prior treatment with immune checkpoint inhibitors (ICIs).
Results also showed that SOT101, either as monotherapy or in combination with pembrolizumab, has a favorable safety profile with manageable treatment-emergent adverse events, and achieved encouraging activity with one ongoing complete response and several long-lasting partial responses in patients who had/had not received previous treatment with ICIs, including those with ICI-resistant tumors.
“Based on these data, we have also established the recommended dosing for the upcoming phase II study. In patients for whom there are other alternative treatment options, this combined strategy could ultimately improve outcomes by potentiating innate and adaptive immune responses to cancer,” concludes Elena Garralda.
Key contributions as expert discussants
Reflective of their expertise in early clinical drug development, several UITM-CaixaResearch contributed to this meeting as invited speakers and discussants at various sessions. As examples, Elena Garralda participated in a Clinical Science Symposium on Bispecifics: Are Two Better Than One? (2), as a discussant for Abstract Discussion 1, Novel Bispecific Antibody Targets for Treatment of Cancer.
During an ASCO 2022 Oral Abstract Session (Track: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology) Irene Braña, a CORE Phase I Clinical Investigator of VHIO’s UITM-CaixaResearch, who was also invited by ASCO’s Scientific Committee, presented on Drugging the Undruggable: TP53 and PPAR-alpha (Abstract Discussion 2) (3).
Putting bispecific antibody AFM24 to the test
Omar Saavedra, also a CORE Phase I Investigator at VHIO’s UITM-CaixaResearch, discussed the design and rationale of two studies evaluating AFM24. This anti-EGFR/CD16A bispecific antibody targets epidermal growth factor receptor-expressing (EGFR+) solid tumors, and is a tetravalent antibody with two specific binding sites for EGFR, and two for CD16A, a receptor expressed by natural killer (NK) cells and macrophages. The mode of action of AFM24 is not to inhibit EGFR signaling, which is overexpressed in tumor cells, but rather to redirect NK cells and macrophages to EGFR-expressing tumor cells to induce cytotoxicity and cellular phagocytosis.
Results of preclinical studies have shown that this novel antibody induces the killing of EGFR+ tumor cell lines, and that its activity is independent of the level of cell surface expression of this receptor. AFM24 can be used to harness patients’ innate immunity to redirect and activate immune cells, and thus overcome cancer drug resistance.
“We are performing the first-in-human multicenter phase I/IIa open-label clinical trials to assess the safety, tolerability, pharmacokinetics, and efficacy of this novel agent. The first is evaluating AFM24 in patients with locally advanced or metastatic treatment-refractory solid cancers that are known to express EGFR,” says Omar Saavedra who presented this study as a poster at ASCO 2022.
The first phase I/IIa study is testing AFM24 as monotherapy in patients with advanced solid tumors (5). The dose escalation part (phase I) was designed to establish the maximum tolerated dose and/or recommended phase II dose of AFM24. In parallel with these ongoing investigations, the dose expansion study (phase II) was initiated to assess the activity of this novel agent in patients with different EGFR-expressing tumors. The primary endpoint is to establish overall response rate in three disease-specific cohorts of patients with clear cell renal cell carcinoma, KRAS-mutated colorectal cancer, and EGFR-mutant non-small cell lung cancer.
Another study, also presented as a poster communication by first author Omar Saavedra (5), is an ongoing phase I/IIa non-randomized dose escalation (phase I) and dose expansion (phase II) study evaluating the activity of this promising bispecific antibody in combination with an anti-PDL-1 antibody, atezolizumab, in patients with advanced EGFR-expressing solid tumors and disease progression on one or more prior lines of therapy.
“Anti-PD-L1 immune checkpoint inhibitors potentiate the anti-tumor activity of a patient’s adaptive immunity, and have shown efficacy as monotherapy. These novel contenders are increasingly being tested in combination with other anti-cancer therapies towards achieving more durable and deeper responses,” explains Omar Saavedra.
Specifically, results of the dose escalation study will establish the maximum tolerated dose and recommended dose of AFM24 plus atezolizumab in each cohort for the phase II investigations that will then assess the overall response rate of this combined approach in patients with advanced, metastatic and treatment refractory disease across various tumor types.
“These trials have been designed to further spur the development of more powerful immune-based strategies aimed at improving treatment outcomes and extending their promise to an increasing number of patient populations,” concludes Omar Saavedra.
References:
- Abstract #: 2502. Elena Garralda, Aung Naing, Vladimir Galvao, Patricia LoRusso, Peter Grell, Philippe A. Cassier, Carlos A. Gomez-Roca, Iphigenie Korakis, David Bechard, Lenka Palova Jelinkova, Irena Adkins, Sascha Tillmanns, Joachim Kiemle-Kallee, Aurelien Marabelle, Stephane Champiat. Interim safety and efficacy results from AURELIO-03: A phase 1 dose escalation study of the IL-2/IL-15 receptor βγ superagonist SOT101 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors. J Clin Oncol 40, 2022 (suppl 16; abstr 2502). https://meetinglibrary.asco.org/record/207281/abstract.
- Corresponding ASCO 2022 session details:
Session Type: Clinical Science Symposium.
Session Title: Bispecifics: Are Two Better Than One?
Track: Special Sessions.
Discussant: Elena Garralda.
https://meetings.asco.org/2022-asco-annual-meeting/14411?presentation=210122#210122.
- Corresponding ASCO 2022 session details:
Session Type: Oral Abstract Session.
Track: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology.
Speaker: Irene Braña.
https://meetings.asco.org/2022-asco-annual-meeting/14356?presentation=213778#213778.
- Abstract # : TPS2672. Omar Saavedra Santa Gadea, Elena Garralda, Juanita S. Lopez, Mark M. Awad, Jacob S. Thomas, Crescens D. Tiu, Daniela Morales-Espinosa, Christa Raab, Bettina Rehbein, Gabriele Hintzen, Kerstin Pietzko, Paulien Ravenstijn, Michael Emig, Anthony B. El-Khoueiry. A phase 1/2a open label, multicenter study to assess the safety, tolerability, pharmacokinetics, and efficacy of AFM24 in patients with advanced solid cancers: Study design and rationale. J Clin Oncol 40, 2022 (suppl 16; abstr TPS2672). https://meetinglibrary.asco.org/record/213282/abstract.
- Abstract # : TPS2673. Omar Saavedra Santa Gadea, Eric Christenson, Anthony B. El-Khoueiry, Andres Cervantes, Christa Raab, Ulrike Gaertner, Kerstin Pietzko, Gabriele Hintzen, Paulien Ravenstijn, Daniela Morales-Espinosa, Juanita S. Lopez. AFM24 in combination with atezolizumab in patients with advanced EGFR-expressing solid tumors: Phase 1/2a study design and rationale. J Clin Oncol 40, 2022 (suppl 16; abstr TPS2673). https://meetinglibrary.asco.org/record/213509/abstract.
