An AstraZeneca/Merck combination showed mostly positive ovarian cancer data, Adaptimmune posted a strong ORR in solid tumors and BioNTech revealed data from a CAR-T cell therapy.
At ESMO on Friday, an AstraZeneca/Merck combination showed mostly positive ovarian cancer data, Adaptimmune posted a strong objective response rate in solid tumors, BioNTech revealed data from a CAR-T cell therapy and Immunocore investors are running scared.
AstraZeneca/Avastin Combo Shines in Ovarian Cancer
AstraZeneca and Merck shared what the companies called landmark five-year-follow-up data for PARP inhibitor Lynparza (olaparib). The data presented was from two Phase III trials, PAOLA-1 and SOLO-1. Ovarian cancer patients treated with Lynparza with and without bevacizumab (Genentech’s Avastin) demonstrated clinically meaningful improvements in overall survival (OS).
Both trials were conducted in biomarker-selected, newly diagnosed patients with advanced ovarian cancer in the first-line maintenance setting.
Data from PAOLA-1 showed Lynparza plus bevacizumab meaningfully extended survival by 65.5% in homologous recombination deficiency (HRD)-positive cancer patients who have survived for five years. That was compared to 48.4% treated with bevacizumab and placebo.
While the subpopulation data was strong, overall data for the combination approach was not statistically significant. AstraZeneca reported Lynparza plus Avastin increased median OS to 56.5 months compared to 51.6 months with bevacizumab alone. These results were in newly diagnosed patients irrespective of HRD status, the company stated. Risk of death was reduced by 45%
In SOLO-1, treatment with Lynparza offered a clinically meaningful improvement in OS compared to placebo in patients with BRCA-mutated newly diagnosed advanced ovarian cancer.
Median OS was not reached with Lynparza compared to 75.2 months in the placebo cohort, AstraZeneca reported. At seven years, 67% of Lynparza patients were alive compared to 47% of placebo patients.
The safety and tolerability profile of Lynparza remained consistent with data from previous clinical trials.
Adaptimmune Posts Positive Data in Solid Tumors
Adaptimmune reported a 44% objective response rate following a single dose of ADP-A2M4CD8 in 25 heavily pre-treated patients with late-stage ovarian, urothelial and head and neck cancers that express MAGE-4, independent of tumor type. These patients were a subset of the Phase I SURPASS trial,
Trial participants had advanced, late-stage metastatic cancers and had received an average of three prior lines of therapy.
Most patients available for assessment experienced meaningful antitumor activity with a disease control rate of 81%, the company announced. For the subset of 25 people with ovarian, urothelial and head & neck cancers, the response rate was 44%. The median duration of response was 12 weeks. Overall in the five different cancer types, Adaptimmune reported a 33% ORR.
Across non-sarcoma tumors, significantly higher response rates were seen against the first-generation MAGE-A4 targeted product afami-cel, Adaptimmune announced. The company stated the safety and efficacy profile of ADP-A2M4CD8 supports further clinical development.
In ovarian cancer, Adaptimmune plans to initiate a Phase II trial in patients with platinum-resistant disease later this year.
BioNTech CAR-T Program Posts Encouraging Data
BioNTech’s CAR-T program for solid tumors is showing positive results in patients with relapsed or refractory advanced solid tumors.
On Friday, Germany-based BioNTech presented follow-up data from a Phase I/II study demonstrating encouraging signs of clinical anti-tumor activity with BNT211, a CAR-T cell therapy. The strongest responses were seen in testicular cancer patients treated at “dose level 2” after lymphodepletion from chemotherapy, BioNTech reported. The company noted an ORR of 57% and a disease control rate of 85% for patients with those dose levels. Of those patients, there was one complete response, three partial responses and two stable disease reports, the announcement detailed.
An efficacy assessment of 21 evaluable patients showed an ORR of 33% and a disease control rate of 67% with one complete response, six partial responses and seven patients with stable disease, BioNTech noted.
Solid tumors included in the Phase I/II study included testicular cancer, ovarian cancer, endometrial cancer, fallopian tube cancer, sarcoma, gastric cancer and one patient with a tumor of unknown primary origin. Adverse events, which included cytokine release syndromes and dose-limiting toxicities were manageable.
BNT211 targets CLDN6-positive solid tumors in combination with a CAR-T cell-amplifying RNA-vaccine dubbed CARVac, which encodes for CLDN6. BNT211 is designed to overcome CAR-T cell therapy limitations in patients with solid tumors.
The European Medicines Agency granted Priority Medicines designation to BNT211 based on initial data seen in patients with testicular cancer. That data, presented earlier this year at the American Association for Cancer Research (AACR), showed a disease control rate of 86% and an ORR of 43%, the company announced at the time.
Investors Negatively React to Immunocore Data
Shares of Immunocore fell nearly 20% after the company shared data from its Phase I off-the-shelf TCR therapy at ESMO.
Data from Immunocore’s early-stage clinical trial showed IMC-F106C, a PRAME×CD3 ImmTAC therapy, activated T cells and was well tolerated by patients.
What may have concerned Immunocore stockholders was that most of the treatment-related adverse reactions reported were related to cytokine release syndrome (CRS), an immune response to the medication. These CRS responses primarily occurred following the initial three doses and did not lead to a discontinuation of treatment nor death in any patient, Immunocore noted in its announcement.
The company reported that doses of IMC-F106C at ≥ 20 mcg were clinically active and showed “consistent and robust interferon gamma induction.” This is a specific marker of T cell activation.
Durable responses were observed in two of six patients with cutaneous melanoma; two of four patients with ovarian cancer; and three of six patients with tebentafusp-naïve uveal melanoma, Immunocore reported. A majority of patients evaluable for circulating tumor DNA (ctDNA) had at least a 50% reduction, the company noted.
