FIH, Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorGerman Cancer Research Center
About this trial
This trial is a first in human (FIH) clinical trial in patients with Colorectal cancer (CRC) after failure of at least three lines of previous therapy aiming to evaluate safety and efficacy of CC-3, a bispecific antibody (bsAb) with CD276xCD3 specificity developed within DKTK. CC-3 binds to CD276 on cancer cells as well as to tumor vessels of CRC, thereby allowing for a dual mode of anti-cancer action. CC-3 was developed in a novel format which not only prolongs serum half-life, but most importantly reduces off-target T cell activation with expected fewer side effects. A similar construct in this format with PSMAxCD3 specificity is presently undergoing clinical evaluation in patients with prostate cancer (NCT04104607), with very favorable safety and preliminary efficacy. The optimized format that CC-3 shares with its PSMAxCD3 "sister molecule" allows for application of effective bsAb doses with expected high anticancer activity. The clinical trial comprises two phases: The first phase is a dose-escalation part to evaluate the maximally tolerated dose (MTD) of CC-3. This is followed by a dose-expansion part to defined the recommended phase II dose. A translational research program comprising, among others, analysis of CC-3 half-life and the induced immune response will serve to better define the mode of action of CC-3.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient is able to understand and comply with the protocol for the duration of the clinical trial including undergoing treatment and scheduled visits and examinations
Patients with progressing metastatic CRC who were previously treated with FOLFOX, FOLFIRI, FOLFOXIRI, TAS-102, or regorafenib, if applicable in combination with anti-VEGFR monoclonal antibody (mAb) and anti-EGFR mAb (the latter, if RAS-wild-type and left sided tumors).
At least one measurable lesion that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessment per RECIST 1.1.
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
Disqualifiers
Other malignancy requiring treatment within the last year except: adequately treated non-melanoma skin cancer and low-grade non-muscle invasive papillary bladder cancer.
Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy
Persistent toxicity (≥ Grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) caused by previous cancer therapy, excluding alopecia and neurotoxicity
Clinical signs of active infection (> grade 2 according to CTCAE version 5.0)
Trial design
Design model
Single group
Treatments tested in this trial
Administration of CC-3
DrugAccelerated titration phase, Standard 3+3 titration phase, expansion phase
Treatment groups
89 Participants
are divided into 1 treatment groupGroup A: Administration of CC-3, a bispecific CD276xCD3 antibodyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety 1-Adverse Events Assessment
Dose escalation and dose expansion part: Characterization of the safety of CC-3 in patients with metastasized CRC, and to define the recommended phase-II dose (RP2D) of CC-3 Adverse events should be documented and recorded continuously. Patients have to be followed for AEs from visit T1V1( treatment week1 Visit 1) up to last clinical trial visit or until all drug-related toxicities have been resolved, whichever is later, or until the investigator assesses AEs as "chronic" or "stable". Each occurrence of an AE must be reported once indicating the CTC (Version 5.0) grade. If the CTC grading of an ongoing AE changes this has to be reported. If an event stops and later restarts, all occurrences must be reported. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA®) v26.0 or higher. All AEs will be graded according to the CTCAEv5.0, except for cytokine release syndrome, which will be graded according to modified criteria by Lee et al. (Lee et al., 2019).
Time frame
Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days2
Safety 2 -Blood Chemistry-Transaminases
AST/SGOT in \[U/l\] ALT/SGPT in \[U/l)
Time frame
Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days3
Safety 3-Hematology-haemoglobin
haemoglobin in \[g/l\]
Time frame
Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days4
Safety 3-Hematology-Red Blood Cells
RBC in \[cells/µl\]
Time frame
Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 daysSponsors and contacts
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Source ClinicalTrials.gov