Abstract CT162: The phase 1b PORTIA study: Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL)
Bibliographic record
Abstract
Abstract Introduction: Pembrolizumab (pembro) has shown clinical activity in r/r DLBCL after failing tisagenlecleucel (tisa), an autologous anti-CD19 chimeric antigen receptor (CAR)-T therapy (Chong et al. Blood. 2017). Methods: PORTIA is a phase 1b, multicenter, open-label trial investigating the safety and efficacy of tisa plus pembro in adult patients (pts) with r/r DLBCL. Pts receive a single tisa IV infusion (target: 0.6-6.0×108 cells) on Day (D)1 and pembro at 200mg every 21 days, for up to 6 doses. Pembro was started on D15 post tisa in Cohort 1, with the option of moving to D8 (Cohort 2) or D22 based on safety profile and dose-limiting toxicities (DLTs). Primary endpoints: proportion of pts receiving pembro per schedule, incidence of DLTs (dose-timing selection phase), overall response rate (dose-expansion phase). Results: As of 5 March 2019, 5 patients were screened for Cohort 1; 4 pts were enrolled. Median age was 54 (range, 35-79). Median follow-up after tisa infusion was 46 days (range, 36-85). Pts received 1.7-3.0×108 CAR-positive T cells and 1, 2, 2, and 4 pembro doses, respectively, with no delays. All 4 pts experienced ≥1 adverse event (AE), with no exacerbation or recurrence of tisa-related AEs post pembro infusion. No pembro-related AEs, DLTs or grade 3/4 treatment-related AEs (TRAEs) were observed (Table 1). All pts experienced initial expansion between D6-15 post-tisa infusion; overall exposure is consistent with that observed in the JULIET trial. Two pts discontinued pembro treatment (after 1 and 2 doses, respectively) due to disease progression. With limited follow-up, 1 partial response has been observed. Table 1.TRAEs and Grade 3/4 AEs Observed in Day 15 Cohort Interim ReadAdverse EventPatients With Grade 3/4 AE, n (%)Patients With Grade 3/4 AE, n (%)Patients With Grade 3/4 TRAE, n (%)Anemia1 (25)a00Cytokine release syndrome01 (25)a0Pancreatitis1 (25)a00Tachycardia01 (25)a0AE, adverse event; TRAE, treatment-related adverse event.aAnemia developed on D14 after tisa infusion but preceding pembro initiation, and again on D36 while the pt was on pembro (during the time from first pembro administration to 30 days after the last pembro administration date). Pancreatitis developed on D28 in the same pt. Both are likely related to lymphoma progression.bOne pt developed grade 2 cytokine release syndrome according to the Lee scale (D7-11) and concomitant sinus tachycardia, both attributed to tisa and resolved prior to pembro infusion; no neurological events occurred. Conclusions: PD-1 blockade with pembro was feasible and showed a manageable safety profile in the first 4 pts. No DLTs or clinically significant exacerbation of AEs were observed. Efficacy and safety data for Cohorts 1 and 2 (D15 and D8) with longer follow-up will be presented at the congress. Clinical trial information: NCT03630159 Citation Format: Ulrich Jaeger, Nina Worel, Joseph P. McGuirk, Peter A. Riedell, Isabelle Fleury, Peter Borchmann, Simon Newsome, Ahmed M. Abdelhady, Alessandra Forcina, Lida Bubuteishvili Pacaud, Edmund K. Waller. The phase 1b PORTIA study: Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT162.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".