TIVDAK® Clinical Studies

14.1 Recurrent or Metastatic Cervical Cancer

innovaTV 301

The efficacy of TIVDAK was evaluated in innovaTV 301 (NCT04697628), an open-label, active-controlled, multicenter, randomized trial that enrolled 502 patients with recurrent or metastatic cervical cancer who had received one or two prior systemic therapy regimens in the recurrent or metastatic setting, including chemotherapy with or without bevacizumab and/or an anti-PD-(L)1 agent. Patients were excluded if they had active ocular surface disease, any prior episode of cicatricial conjunctivitis or ocular SJS, Grade ≥2 peripheral neuropathy, or clinically significant bleeding issues or risks.

Patients were randomized (1:1) to receive either TIVDAK 2 mg/kg intravenously every 3 weeks (n=253) or investigator’s choice of chemotherapy (n=249) consisting of topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed, until unacceptable toxicity or disease progression. Randomization was stratified by prior treatment with bevacizumab (yes or no), prior anti-PD-(L)1 therapy (yes or no), region (US, Europe, or Other), and ECOG performance status (0 or 1).

Patients were treated until disease progression or unacceptable toxicity. Tumor response assessments were performed every 6 weeks for the first 30 weeks and every 12 weeks thereafter.

The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were progression free survival (PFS) and confirmed objective response rate (ORR) as assessed by investigator using RECIST v1.1.

The median age was 50 years (range: 26 to 80); 49% were White, 36% were Asian, 10% were not reported, 3% were American Indian or Alaskan Native, and 2% were Black; 20% were Hispanic/Latino; and baseline ECOG performance status was 0 (54%) or 1 (46%). Sixty-three percent of patients had squamous cell carcinoma, 32% had adenocarcinoma, and 5% had adenosquamous histology. Ninety percent of patients had extrapelvic disease; 61% of patients had received 1 prior line of systemic therapy, and 38% had 2 prior lines of systemic therapy. All patients received prior chemotherapy; 64% received prior bevacizumab and 27% received prior anti-PD-1 or anti-PD-L1 therapy. Patients on the control arm received gemcitabine (44%), pemetrexed (32%), topotecan (8%), vinorelbine (7%), or irinotecan (6%).

Statistically significant improvements in OS, PFS, and ORR were demonstrated for TIVDAK compared with chemotherapy.

Table 9 and Figure 2 summarize the efficacy results from innovaTV 301.

Figure 2. Kaplan Meier Plot of Overall Survival

innovaTV 204

The efficacy of TIVDAK was evaluated in innovaTV 204 (NCT03438396), an open-label, multicenter, single-arm trial that treated 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Patients were excluded if they had active ocular surface disease, any prior episode of cicatricial conjunctivitis or ocular SJS, Grade ≥2 peripheral neuropathy or known coagulation defects leading to an increased risk of bleeding.

Patients received TIVDAK 2 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. Tumor response assessments were performed every 6 weeks for the first 30 weeks and every 12 weeks thereafter.

The median age was 50 years (range: 31 to 78); 95% were White, 2% were Asian, and 1% were Black. Six percent of patients were Hispanic or Latino. Sixty-eight percent of patients had squamous cell carcinoma, 27% had adenocarcinoma, and 5% had adenosquamous histology. ECOG performance status was 0 (58%) or 1 (42%). Seventy percent of patients had received 1 prior line of systemic therapy, and 30% had 2 prior lines of systemic therapy. Sixty-nine percent of patients previously received bevacizumab as part of their prior systemic therapy. Sixty-three percent received bevacizumab in combination with chemotherapy (paclitaxel and cisplatin or carboplatin, or paclitaxel and topotecan) as first-line therapy.

The major efficacy outcome measures were confirmed objective response rate (ORR) as assessed by an independent review committee (IRC) using RECIST v1.1 criteria and duration of response (DOR).

Efficacy results are presented in Table 10.