Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor
AFNT-211 is a cellular therapy consisting of autologous CD4+ and CD8+ T cells engineered to
express a human leukocyte antigen-A (HLA-A)*11:01-restricted Kirsten rat sarcoma (KRAS)
G12V-specific transgenic T cell receptor (TCR), the wildtype CD8α/β coreceptor, and a
FAS-41BB switch receptor. AFNT-211 is being developed by Affini-T Therapeutics, Inc.
(hereafter, "the Sponsor") for the treatment of patients with malignant solid tumors. The
primary purpose of this study is to assess the safety and tolerability of AFNT-211 in
subjects who are HLA-A*11:01 positive with advanced or metastatic cancers that harbor a KRAS
G12V mutation, as well as determine the optimal biological dose (OBD) and recommended Phase
II dose (RP2D) of AFNT-211 in this population. This study will also evaluate the preliminary
anti-tumor activity of AFNT-211.
A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of Taletrectinib in Patients With Advanced or Metastatic ROS1 Positive NSCLC and Other Solid Tumors
This is a global Phase 2, multicenter, single-arm, open label study of taletrectinib in
patients of NSCLC harboring with ROS1 fusion gene.
About 224 patients will be enrolled and divided into 6 cohorts, depending on past history of
ROS1 TKI treatment.
In the cohorts open to enrollment, taletrectinib will be administered either 400mg or 600mg
once daily in 21-day cycles. In one cohort, this will be in combination with carboplatin and
pemetrexed both administered by IV infusion in 21-day cycles for 4 cycles. Patients will
continue with the treatment on taletrectinib until progression of disease as determined by
the investigator.
The tumor response evaluation will be conducted on a regular basis until progression of
disease. Long-term survival follow up will be conducted as well.
A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects With Advanced Solid Tumors
ASTX029 is a synthetic small molecule inhibitor of extracellular signal-regulated kinases
(ERKs) 1/2. ASTX029 has not been previously evaluated in human subjects. The Phase 1 portion
of this study will assess safety and determine the maximum tolerated dose, the recommended
Phase 2 dose (RP2D), and the recommended dosing regimen of ASTX029 administered orally. The
Phase 2 portion will assess preliminary clinical activity in tumors characterized by gene
aberrations in the mitogen-activated protein kinase (MAPK) signal pathway that may confer
sensitivity to ASTX029.
First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-Driven Advanced Solid Tumors
This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A)
followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101
plus pembrolizumab.
The study population in dose escalation (Part A) of single agent BCA101 consists of subjects
with EGFR-driven advanced solid tumors refractory to standard of care or for whom no standard
of care is available. Dose escalation (Part A) of combination BCA101 and pembrolizumab
consists of subjects with either Squamous Cell Carcinoma of the Head and Neck (HNSCC) or
Squamous Cell Carcinoma of the Anal Canal (SCCAC) whose tumors are refractory to standard of
care or for whom no standard of care is available.
Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is
determined, the study will continue with expansion cohorts (Part B) with select tumor types.
Expansion cohorts for single agent BCA101 will include cutaneous squamous cell carcinoma.
Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC
and 2) SCCAC.
Phase 1/2 Dose Escalation and Cohort Expansion Study Evaluating MCLA-158 (Petosemtamab) as Single Agent or in Combination in Advanced Solid Tumors
Study Design:
This open label, multicenter, first-in-human study consists of 2 parts. Part 1 is a dose
escalation to find the recommended Phase II dose (RP2D) of MCLA-158 studying patients with
metastatic colorectal cancer. Enrollment in the dose escalation part has been completed.
Dose expansion (single-agent cohorts) In an expansion part of the study, the activity,
safety, and tolerability of MCLA-158 at 1500 mg every 2 weeks (Q2W) (preliminary RP2D) as a
single agent will be evaluated in cohorts of selected solid tumor indications with dependency
on EGFR signaling. Eligible solid tumor indications may include locally advanced unresectable
or metastatic HNSCC, gastric/gastroesophageal junction adenocarcinoma (GEA) with EGFR
amplification and/or high EGFR expression, esophageal carcinoma and pancreatic
adenocarcinoma. Additionally, safety will be characterized at two dose levels in this
setting.
Dose expansion (in combination with pembrolizumab cohort)
MCLA-158 in combination with pembrolizumab will be explored first in HNSCC patients eligible
to receive pembrolizumab as first-line monotherapy. Other expansion cohorts may be considered
for combination treatment in the future.
An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors
RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly
destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open
label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to
evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of
RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors. The study will include a dose escalation phase for single agent RP1, an
expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified
tumor types for the combination therapy.
Pilot Study of Resection and GammaTile Followed by Concomitant External Beam Radiation Therapy (EBRT) and Temozolomide (TMZ) and Adjuvant in Newly Diagnosed Glioblastoma (GBM)
This study seeks to explore if GT, given its unique radiobiological and physical
characteristics, may permit safe dose escalation and intensification and thereby provide a
benefit to newly diagnosed GBM patients in terms of OS and LC when incorporated into the
framework of the Stupp protocol. In this study, GT is utilized as an upfront boost at the
time of maximum safe resection and dosimetrically integrated into what is otherwise standard
of care therapy.
Patients in this study will receive doses from two different forms of radiation treatment,
initially from Cs-131 BT with GT and subsequently from fractionated EBRT. In order to ensure
both patient safety and adequacy of treatment, we have chosen to stipulate and evaluate the
coverage of the tumor volumes and OARs using the doses combined from both these treatments.
The intention is that with this methodology the doses received by the target volumes and
relevant OARs from the implanted Cs-131 will be accounted for during EBRT treatment planning.
This dose combination, accomplished using radiobiological modeling, is frequently undertaken
in breast, prostate, and gynecological malignancies. To provide oversight and planning
feedback, the first three patients enrolled at each site will undergo review by the Clinical
Oversight Committee (COC) at two points for each patient, once after the GT implant, and
before starting EBRT treatment.
Powered by
SC CTSI